PLoS Genetics via MedWorm.com MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'PLoS Genetics' source. Mon, 06 Feb 2012 09:32:20 +0100 Raf1 Is a DCAF for the Rik1 DDB1-Like Protein and Has Separable Roles in siRNA Generation and Chromatin Modification http://www.medworm.com/index.php?rid=5654625&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fxh5JZ4X0IJM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002499 by Alessia Buscaino, Sharon A. White, Douglas R. Houston, Erwan Lejeune, Femke Simmer, Flavia de Lima Alves, Piyush T. Diyora, Takeshi Urano, Elizabeth H. Bayne, Juri Rappsilber, Robin C. Allshire Non-coding transcription can trigger histone post-translational modifications forming specialized chromatin. In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. CLRC mediates H3K9 methylation and siRNA production; it also displays E3-ubiquitin ligase activity in vitro. DCAFs act as substrate receptors for E3 ligases and may couple ubiquitination with histone methylation. Here, structural alignment and mutation of signature WDxR motifs in Raf1 indicate that it is a DCAF for CLRC. We demons... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654625 Thu, 02 Feb 2012 05:00:00 +0100 5654625 Reduction of NADPH-Oxidase Activity Ameliorates the Cardiovascular Phenotype in a Mouse Model of Williams-Beuren Syndrome http://www.medworm.com/index.php?rid=5654624&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FuAbLvKgR1_E%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002458 by Victoria Campuzano, Maria Segura-Puimedon, Verena Terrado, Carolina Sánchez-Rodríguez, Mathilde Coustets, Mauricio Menacho-Márquez, Julián Nevado, Xosé R. Bustelo, Uta Francke, Luis A. Pérez-Jurado A hallmark feature of Williams-Beuren Syndrome (WBS) is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX)–mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated wi... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654624 Thu, 02 Feb 2012 05:00:00 +0100 5654624 The Empirical Power of Rare Variant Association Methods: Results from Sanger Sequencing in 1,998 Individuals http://www.medworm.com/index.php?rid=5654623&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F0KADESmYKNA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002496 by Martin Ladouceur, Zari Dastani, Yurii S. Aulchenko, Celia M. T. Greenwood, J. Brent Richards The role of rare genetic variation in the etiology of complex disease remains unclear. However, the development of next-generation sequencing technologies offers the experimental opportunity to address this question. Several novel statistical methodologies have been recently proposed to assess the contribution of rare variation to complex disease etiology. Nevertheless, no empirical estimates comparing their relative power are available. We therefore assessed the parameters that influence their statistical power in 1,998 individuals Sanger-sequenced at seven genes by modeling different distributions of effect, proportions of causal variants, and direction of the associations (deleterious, p... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654623 Thu, 02 Feb 2012 05:00:00 +0100 5654623 The Mitochondrial Chaperone Protein TRAP1 Mitigates α-Synuclein Toxicity http://www.medworm.com/index.php?rid=5654622&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FHuCFFiMk6ZI%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002488 by Erin K. Butler, Aaron Voigt, A. Kathrin Lutz, Jane P. Toegel, Ellen Gerhardt, Peter Karsten, Björn Falkenburger, Andrea Reinartz, Konstanze F. Winklhofer, Jörg B. Schulz Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T]α-Synuclein–induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T]α-Synuclein expression. In addition, decreased ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654622 Thu, 02 Feb 2012 05:00:00 +0100 5654622 Inter-Homolog Crossing-Over and Synapsis in Arabidopsis Meiosis Are Dependent on the Chromosome Axis Protein AtASY3 http://www.medworm.com/index.php?rid=5654621&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FPqmopnMv-Is%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002507 In this study we have analysed AtASY3, a coiled-coil domain protein that is required for normal meiosis in Arabidopsis. Analysis of an Atasy3-1 mutant reveals that loss of the protein compromises chromosome axis formation and results in reduced numbers of meiotic crossovers (COs). Although the frequency of DNA double-strand breaks (DSBs) appears moderately reduced in Atasy3-1, the main recombination defect is a reduction in the formation of COs. Immunolocalization studies in wild-type meiocytes indicate that the HORMA protein AtASY1, which is related to Hop1 in budding yeast, forms hyper-abundant domains along the chromosomes that are spatially associated with DSBs and early recombination pathway proteins. Loss of AtASY3 disrupts the axial organization of AtASY1. Furthermore we show that t... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654621 Thu, 02 Feb 2012 05:00:00 +0100 5654621 The Williams-Beuren Syndrome—A Window into Genetic Variants Leading to the Development of Cardiovascular Disease http://www.medworm.com/index.php?rid=5654620&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Focqpak4NpgI%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002479 by Gregory N. Adams, Alvin H. Schmaier (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654620 Thu, 02 Feb 2012 05:00:00 +0100 5654620 Evaluation of the Role of Functional Constraints on the Integrity of an Ultraconserved Region in the Genus Drosophila http://www.medworm.com/index.php?rid=5654619&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F4wCTO270jVo%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002475 by Carlos Díaz-Castillo, Xiao-Qin Xia, José M. Ranz Why gene order is conserved over long evolutionary timespans remains elusive. A common interpretation is that gene order conservation might reflect the existence of functional constraints that are important for organismal performance. Alteration of the integrity of genomic regions, and therefore of those constraints, would result in detrimental effects. This notion seems especially plausible in those genomes that can easily accommodate gene reshuffling via chromosomal inversions since genomic regions free of constraints are likely to have been disrupted in one or more lineages. Nevertheless, no empirical test has been performed to this notion. Here, we disrupt one of the largest conserved genomic regions of the Drosophila genome by... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654619 Thu, 02 Feb 2012 05:00:00 +0100 5654619 Loss of Function of the Cik1/Kar3 Motor Complex Results in Chromosomes with Syntelic Attachment That Are Sensed by the Tension Checkpoint http://www.medworm.com/index.php?rid=5654618&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F3A2AN_6B7BE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002492 by Fengzhi Jin, Hong Liu, Ping Li, Hong-Guo Yu, Yanchang Wang The attachment of sister kinetochores by microtubules emanating from opposite spindle poles establishes chromosome bipolar attachment, which generates tension on chromosomes and is essential for sister-chromatid segregation. Syntelic attachment occurs when both sister kinetochores are attached by microtubules from the same spindle pole and this attachment is unable to generate tension on chromosomes, but a reliable method to induce syntelic attachments is not available in budding yeast. The spindle checkpoint can sense the lack of tension on chromosomes as well as detached kinetochores to prevent anaphase onset. In budding yeast Saccharomyces cerevisiae, tension checkpoint proteins Aurora/Ipl1 kinase and centromere-localize... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654618 Thu, 02 Feb 2012 05:00:00 +0100 5654618 Down-Regulating Sphingolipid Synthesis Increases Yeast Lifespan http://www.medworm.com/index.php?rid=5654617&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FwVYtGaP26E4%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002493 by Xinhe Huang, Jun Liu, Robert C. Dickson Knowledge of the mechanisms for regulating lifespan is advancing rapidly, but lifespan is a complex phenotype and new features are likely to be identified. Here we reveal a novel approach for regulating lifespan. Using a genetic or a pharmacological strategy to lower the rate of sphingolipid synthesis, we show that Saccharomyces cerevisiae cells live longer. The longer lifespan is due in part to a reduction in Sch9 protein kinase activity and a consequent reduction in chromosomal mutations and rearrangements and increased stress resistance. Longer lifespan also arises in ways that are independent of Sch9 or caloric restriction, and we speculate on ways that sphingolipids might mediate these aspects of increased lifespan. Sch9 and its mammalia... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5654617 Thu, 02 Feb 2012 05:00:00 +0100 5654617 Inference of Population Structure using Dense Haplotype Data http://www.medworm.com/index.php?rid=5633739&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fq2TvZh_eoXk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002453 We present multiple lines of evidence that, while many methods capture similar information among strongly differentiated groups, more subtle population structure in human populations is consistently present at a much finer level than currently available geographic labels and is only captured by the haplotype-based approach. The software used for this article, ChromoPainter and fineSTRUCTURE, is available from http://www.paintmychromosomes.com/. (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633739 Thu, 26 Jan 2012 05:00:00 +0100 5633739 Sequencing of Pooled DNA Samples (Pool-Seq) Uncovers Complex Dynamics of Transposable Element Insertions in Drosophila melanogaster http://www.medworm.com/index.php?rid=5633738&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fug6QQFNNU7E%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002487 by Robert Kofler, Andrea J. Betancourt, Christian Schlötterer Transposable elements (TEs) are mobile genetic elements that parasitize genomes by semi-autonomously increasing their own copy number within the host genome. While TEs are important for genome evolution, appropriate methods for performing unbiased genome-wide surveys of TE variation in natural populations have been lacking. Here, we describe a novel and cost-effective approach for estimating population frequencies of TE insertions using paired-end Illumina reads from a pooled population sample. Importantly, the method treats insertions present in and absent from the reference genome identically, allowing unbiased TE population frequency estimates. We apply this method to data from a natural Drosophila melanogaster populati... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633738 Thu, 26 Jan 2012 05:00:00 +0100 5633738 Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations http://www.medworm.com/index.php?rid=5633737&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FD7CdCXRwmP8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002467 by Michael P. Heaton, Michael L. Clawson, Carol G. Chitko-Mckown, Kreg A. Leymaster, Timothy P. L. Smith, Gregory P. Harhay, Stephen N. White, Lynn M. Herrmann-Hoesing, Michelle R. Mousel, Gregory S. Lewis, Theodore S. Kalbfleisch, James E. Keen, William W. Laegreid Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633737 Thu, 26 Jan 2012 05:00:00 +0100 5633737 A Flexible Bayesian Model for Studying Gene–Environment Interaction http://www.medworm.com/index.php?rid=5633736&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fz-4dQMzdwy4%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002482 by Kai Yu, Sholom Wacholder, William Wheeler, Zhaoming Wang, Neil Caporaso, Maria Teresa Landi, Faming Liang An important follow-up step after genetic markers are found to be associated with a disease outcome is a more detailed analysis investigating how the implicated gene or chromosomal region and an established environment risk factor interact to influence the disease risk. The standard approach to this study of gene–environment interaction considers one genetic marker at a time and therefore could misrepresent and underestimate the genetic contribution to the joint effect when one or more functional loci, some of which might not be genotyped, exist in the region and interact with the environment risk factor in a complex way. We develop a more global approach based on a Bayesian ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633736 Thu, 26 Jan 2012 05:00:00 +0100 5633736 High-Density SNP Mapping of the HLA Region Identifies Multiple Independent Susceptibility Loci Associated with Selective IgA Deficiency http://www.medworm.com/index.php?rid=5633735&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FIf4nUQXfepk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002476 by Ricardo C. Ferreira, Qiang Pan-Hammarström, Robert R. Graham, Gumersindo Fontán, Annette T. Lee, Ward Ortmann, Ning Wang, Elena Urcelay, Miguel Fernández-Arquero, Concepción Núñez, Gudmundur Jorgensen, Björn R. Ludviksson, Sinikka Koskinen, Katri Haimila, Leonid Padyukov, Peter K. Gregersen, Lennart Hammarström, Timothy W. Behrens Selective IgA deficiency (IgAD; serum IgA (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633735 Thu, 26 Jan 2012 05:00:00 +0100 5633735 USF-1 Is Critical for Maintaining Genome Integrity in Response to UV-Induced DNA Photolesions http://www.medworm.com/index.php?rid=5633734&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FQi4LmrOrjwk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002470 by Yorann Baron, Sébastien Corre, Nicolas Mouchet, Sophie Vaulont, Sharon Prince, Marie-Dominique Galibert An important function of all organisms is to ensure that their genetic material remains intact and unaltered through generations. This is an extremely challenging task since the cell's DNA is constantly under assault by endogenous and environmental agents. To protect against this, cells have evolved effective mechanisms to recognize DNA damage, signal its presence, and mediate its repair. While these responses are expected to be highly regulated because they are critical to avoid human diseases, very little is known about the regulation of the expression of genes involved in mediating their effects. The Nucleotide Excision Repair (NER) is the major DNA–repair process involved ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633734 Thu, 26 Jan 2012 05:00:00 +0100 5633734 Sex Pheromone Evolution Is Associated with Differential Regulation of the Same Desaturase Gene in Two Genera of Leafroller Moths http://www.medworm.com/index.php?rid=5633733&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FhWsCfwLAMuA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002489 by Jérôme Albre, Marjorie A. Liénard, Tamara M. Sirey, Silvia Schmidt, Leah K. Tooman, Colm Carraher, David R. Greenwood, Christer Löfstedt, Richard D. Newcomb Chemical signals are prevalent in sexual communication systems. Mate recognition has been extensively studied within the Lepidoptera, where the production and recognition of species-specific sex pheromone signals are typically the defining character. While the specific blend of compounds that makes up the sex pheromones of many species has been characterized, the molecular mechanisms underpinning the evolution of pheromone-based mate recognition systems remain largely unknown. We have focused on two sets of sibling species within the leafroller moth genera Ctenopseustis and Planotortrix that have rapidly evolved the use of ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633733 Thu, 26 Jan 2012 05:00:00 +0100 5633733 Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity http://www.medworm.com/index.php?rid=5633732&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F8EpGPE2CKLs%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002448 In this study, we asked whether cytokinin and components of cytokinin signaling contribute to plant immunity. We demonstrate that cytokinin levels in Arabidopsis are important in determining the amplitude of immune responses, ultimately influencing the outcome of plant–pathogen interactions. We show that high concentrations of cytokinin lead to increased defense responses to a virulent oomycete pathogen, through a process that is dependent on salicylic acid (SA) accumulation and activation of defense gene expression. Surprisingly, treatment with lower concentrations of cytokinin results in increased susceptibility. These functions for cytokinin in plant immunity require a host phosphorelay system and are mediated in part by type-A response regulators, which act as negative regulators of ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633732 Thu, 26 Jan 2012 05:00:00 +0100 5633732 A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation http://www.medworm.com/index.php?rid=5633731&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FWWLjxH7pJ0I%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002480 by Silvia Naitza, Eleonora Porcu, Maristella Steri, Dennis D. Taub, Antonella Mulas, Xiang Xiao, James Strait, Mariano Dei, Sandra Lai, Fabio Busonero, Andrea Maschio, Gianluca Usala, Magdalena Zoledziewska, Carlo Sidore, Ilenia Zara, Maristella Pitzalis, Alessia Loi, Francesca Virdis, Roberta Piras, Francesca Deidda, Michael B. Whalen, Laura Crisponi, Antonio Concas, Carlo Podda, Sergio Uzzau, Paul Scheet, Dan L. Longo, Edward Lakatta, Gonçalo R. Abecasis, Antonio Cao, David Schlessinger, Manuela Uda, Serena Sanna, Francesco Cucca Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633731 Thu, 26 Jan 2012 05:00:00 +0100 5633731 Heterochromatin Formation Promotes Longevity and Represses Ribosomal RNA Synthesis http://www.medworm.com/index.php?rid=5633730&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FfZOYIswM7UA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002473 by Kimberly Larson, Shian-Jang Yan, Amy Tsurumi, Jacqueline Liu, Jun Zhou, Kriti Gaur, Dongdong Guo, Thomas H. Eickbush, Willis X. Li Organismal aging is influenced by a multitude of intrinsic and extrinsic factors, and heterochromatin loss has been proposed to be one of the causes of aging. However, the role of heterochromatin in animal aging has been controversial. Here we show that heterochromatin formation prolongs lifespan and controls ribosomal RNA synthesis in Drosophila. Animals with decreased heterochromatin levels exhibit a dramatic shortening of lifespan, whereas increasing heterochromatin prolongs lifespan. The changes in lifespan are associated with changes in muscle integrity. Furthermore, we show that heterochromatin levels decrease with normal aging and that heterochro... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633730 Thu, 26 Jan 2012 05:00:00 +0100 5633730 A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese http://www.medworm.com/index.php?rid=5633729&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FvvJUWT98z40%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002455 by Yukinori Okada, Kenichi Shimane, Yuta Kochi, Tomoko Tahira, Akari Suzuki, Koichiro Higasa, Atsushi Takahashi, Tetsuya Horita, Tatsuya Atsumi, Tomonori Ishii, Akiko Okamoto, Keishi Fujio, Michito Hirakata, Hirofumi Amano, Yuya Kondo, Satoshi Ito, Kazuki Takada, Akio Mimori, Kazuyoshi Saito, Makoto Kamachi, Yasushi Kawaguchi, Katsunori Ikari, Osman Wael Mohammed, Koichi Matsuda, Chikashi Terao, Koichiro Ohmura, Keiko Myouzen, Naoya Hosono, Tatsuhiko Tsunoda, Norihiro Nishimoto, Tsuneyo Mimori, Fumihiko Matsuda, Yoshiya Tanaka, Takayuki Sumida, Hisashi Yamanaka, Yoshinari Takasaki, Takao Koike, Takahiko Horiuchi, Kenshi Hayashi, Michiaki Kubo, Naoyuki Kamatani, Ryo Yamada, Yusuke Nakamura, Kazuhiko Yamamoto Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multip... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5633729 Thu, 26 Jan 2012 05:00:00 +0100 5633729 Insulin Signaling Regulates Fatty Acid Catabolism at the Level of CoA Activation http://www.medworm.com/index.php?rid=5615575&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FEfmIyN7auPM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002478 by Xiaojun Xu, Peddinti Gopalacharyulu, Tuulikki Seppänen-Laakso, Anna-Liisa Ruskeepää, Cho Cho Aye, Brian P. Carson, Silvia Mora, Matej Orešič, Aurelio A. Teleman The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fa... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615575 Thu, 19 Jan 2012 05:00:00 +0100 5615575 A Spontaneous Mutation of the Rat Themis Gene Leads to Impaired Function of Regulatory T Cells Linked to Inflammatory Bowel Disease http://www.medworm.com/index.php?rid=5615574&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FpIR0Qd0ZhZQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002461 by Marianne Chabod, Christophe Pedros, Lucille Lamouroux, Céline Colacios, Isabelle Bernard, Dominique Lagrange, Daniela Balz-Hara, Jean-Francois Mosnier, Christian Laboisse, Nathalie Vergnolle, Olivier Andreoletti, Marie-Paule Roth, Roland Liblau, Gilbert J. Fournié, Abdelhadi Saoudi, Anne S. Dejean Spontaneous or chemically induced germline mutations, which lead to Mendelian phenotypes, are powerful tools to discover new genes and their functions. Here, we report an autosomal recessive mutation that occurred spontaneously in a Brown-Norway (BN) rat colony and was identified as causing marked T cell lymphopenia. This mutation was stabilized in a new rat strain, named BNm for “BN mutated.” In BNm rats, we found that the T cell lymphopenia originated in the thymus, was intrinsic ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615574 Thu, 19 Jan 2012 05:00:00 +0100 5615574 Adaptation and Preadaptation of Salmonella enterica to Bile http://www.medworm.com/index.php?rid=5615573&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FFLben3ku8tE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002459 This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile. Sublethal concentrations of the bile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress response and other stress responses. The crucial role of the general stress response in adaptation to bile is supported by the observation that RpoS− mutants are bile-sensitive. While adaptation to bile involves a response by the bacterial population, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containing a lethal concentration of bile yields bile-resistant colo... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615573 Thu, 19 Jan 2012 05:00:00 +0100 5615573 Progressive Polycomb Assembly on H3K27me3 Compartments Generates Polycomb Bodies with Developmentally Regulated Motion http://www.medworm.com/index.php?rid=5615572&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fu0RNoxXPZbY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002465 by Thierry Cheutin, Giacomo Cavalli Polycomb group (PcG) proteins are conserved chromatin factors that maintain silencing of key developmental genes outside of their expression domains. Recent genome-wide analyses showed a Polycomb (PC) distribution with binding to discrete PcG response elements (PREs). Within the cell nucleus, PcG proteins localize in structures called PC bodies that contain PcG-silenced genes, and it has been recently shown that PREs form local and long-range spatial networks. Here, we studied the nuclear distribution of two PcG proteins, PC and Polyhomeotic (PH). Thanks to a combination of immunostaining, immuno-FISH, and live imaging of GFP fusion proteins, we could analyze the formation and the mobility of PC bodies during fly embryogenesis as well as compare the... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615572 Thu, 19 Jan 2012 05:00:00 +0100 5615572 Unraveling the Regulatory Mechanisms Underlying Tissue-Dependent Genetic Variation of Gene Expression http://www.medworm.com/index.php?rid=5615571&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FJPUuiRkCreo%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002431 by Jingyuan Fu, Marcel G. M. Wolfs, Patrick Deelen, Harm-Jan Westra, Rudolf S. N. Fehrmann, Gerard J. te Meerman, Wim A. Buurman, Sander S. M. Rensen, Harry J. M. Groen, Rinse K. Weersma, Leonard H. van den Berg, Jan Veldink, Roel A. Ophoff, Harold Snieder, David van Heel, Ritsert C. Jansen, Marten H. Hofker, Cisca Wijmenga, Lude Franke It is known that genetic variants can affect gene expression, but it is not yet completely clear through what mechanisms genetic variation mediate this expression. We therefore compared the cis-effect of single nucleotide polymorphisms (SNPs) on gene expression between blood samples from 1,240 human subjects and four primary non-blood tissues (liver, subcutaneous, and visceral adipose tissue and skeletal muscle) from 85 subjects. We characterized four ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615571 Thu, 19 Jan 2012 05:00:00 +0100 5615571 Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks http://www.medworm.com/index.php?rid=5615570&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FJlU3WmwUDEE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002460 by Pierre Caron, Francois Aymard, Jason S. Iacovoni, Sébastien Briois, Yvan Canitrot, Beatrix Bugler, Laurent Massip, Ana Losada, Gaëlle Legube Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that coh... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615570 Thu, 19 Jan 2012 05:00:00 +0100 5615570 A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli http://www.medworm.com/index.php?rid=5615569&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FYyrNri0CylA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002443 by Olin K. Silander, Nela Nikolic, Alon Zaslaver, Anat Bren, Ilya Kikoin, Uri Alon, Martin Ackermann Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615569 Thu, 19 Jan 2012 05:00:00 +0100 5615569 RIC-7 Promotes Neuropeptide Secretion http://www.medworm.com/index.php?rid=5615568&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FOsY97waAMSQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002464 by Yingsong Hao, Zhitao Hu, Derek Sieburth, Joshua M. Kaplan Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs) respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV–mediated secretion. (Source: PLoS Genet... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615568 Thu, 19 Jan 2012 05:00:00 +0100 5615568 DNA Methylation and Gene Expression Changes in Monozygotic Twins Discordant for Psoriasis: Identification of Epigenetically Dysregulated Genes http://www.medworm.com/index.php?rid=5615567&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fj5CF6LRzR6E%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002454 by Kristina Gervin, Magnus D. Vigeland, Morten Mattingsdal, Martin Hammerø, Heidi Nygård, Anne O. Olsen, Ingunn Brandt, Jennifer R. Harris, Dag E. Undlien, Robert Lyle Monozygotic (MZ) twins do not show complete concordance for many complex diseases; for example, discordance rates for autoimmune diseases are 20%–80%. MZ discordance indicates a role for epigenetic or environmental factors in disease. We used MZ twins discordant for psoriasis to search for genome-wide differences in DNA methylation and gene expression in CD4+ and CD8+ cells using Illumina's HumanMethylation27 and HT-12 expression assays, respectively. Analysis of these data revealed no differentially methylated or expressed genes between co-twins when analyzed separately, although we observed a substantial amount of... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615567 Thu, 19 Jan 2012 05:00:00 +0100 5615567 Tempo and Mode in Evolution of Transcriptional Regulation http://www.medworm.com/index.php?rid=5615566&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F9Olahzxy9kE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002432 by Kacy L. Gordon, Ilya Ruvinsky Perennial questions of evolutionary biology can be applied to gene regulatory systems using the abundance of experimental data addressing gene regulation in a comparative context. What is the tempo (frequency, rate) and mode (way, mechanism) of transcriptional regulatory evolution? Here we synthesize the results of 230 experiments performed on insects and nematodes in which regulatory DNA from one species was used to drive gene expression in another species. General principles of regulatory evolution emerge. Gene regulatory evolution is widespread and accumulates with genetic divergence in both insects and nematodes. Divergence in cis is more common than divergence in trans. Coevolution between cis and trans shows a particular increase over greater evo... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615566 Thu, 19 Jan 2012 05:00:00 +0100 5615566 Nucleolar Association and Transcriptional Inhibition through 5S rDNA in Mammals http://www.medworm.com/index.php?rid=5615565&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FgFVwarpk5CQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002468 by Andrew M. Fedoriw, Joshua Starmer, Della Yee, Terry Magnuson Changes in the spatial positioning of genes within the mammalian nucleus have been associated with transcriptional differences and thus have been hypothesized as a mode of regulation. In particular, the localization of genes to the nuclear and nucleolar peripheries is associated with transcriptional repression. However, the mechanistic basis, including the pertinent cis- elements, for such associations remains largely unknown. Here, we provide evidence that demonstrates a 119 bp 5S rDNA can influence nucleolar association in mammals. We found that integration of transgenes with 5S rDNA significantly increases the association of the host region with the nucleolus, and their degree of association correlates strongly with re... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5615565 Thu, 19 Jan 2012 05:00:00 +0100 5615565 A Half-Century of Inspiration: An Interview with Hamilton Smith http://www.medworm.com/index.php?rid=5590810&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fmvm-GiOVbEM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002466 by Jane Gitschier (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590810 Thu, 12 Jan 2012 05:00:00 +0100 5590810 Cdc5-Dependent Asymmetric Localization of Bfa1 Fine-Tunes Timely Mitotic Exit http://www.medworm.com/index.php?rid=5590809&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FcCp56lFdTCE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002450 by Junwon Kim, Guangming Luo, Young Yil Bahk, Kiwon Song In budding yeast, the major regulator of the mitotic exit network (MEN) is Tem1, a GTPase, which is inhibited by the GTPase-activating protein (GAP), Bfa1/Bub2. Asymmetric Bfa1 localization to the bud-directed spindle pole body (SPB) during metaphase also controls mitotic exit, but the molecular mechanism and function of this localization are not well understood, particularly in unperturbed cells. We identified four novel Cdc5 target residues within the Bfa1 C-terminus: 452S, 453S, 454S, and 559S. A Bfa1 mutant in which all of these residues had been changed to alanine (Bfa14A) persisted on both SPBs at anaphase and was hypo-phosphorylated, despite retaining its GAP activity for Tem1. A Bfa1 phospho-mimetic mutant in which all o... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590809 Thu, 12 Jan 2012 05:00:00 +0100 5590809 Parallel Mapping and Simultaneous Sequencing Reveals Deletions in BCAN and FAM83H Associated with Discrete Inherited Disorders in a Domestic Dog Breed http://www.medworm.com/index.php?rid=5590808&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FTbVWnFGJMsY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002462 by Oliver P. Forman, Jacques Penderis, Claudia Hartley, Louisa J. Hayward, Sally L. Ricketts, Cathryn S. Mellersh The domestic dog (Canis familiaris) segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS) and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF), a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (C... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590808 Thu, 12 Jan 2012 05:00:00 +0100 5590808 Genetic Evidence for an Indispensable Role of Somatic Embryogenesis Receptor Kinases in Brassinosteroid Signaling http://www.medworm.com/index.php?rid=5590807&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FjzUz6g0Z1ZI%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002452 by Xiaoping Gou, Hongju Yin, Kai He, Junbo Du, Jing Yi, Shengbao Xu, Honghui Lin, Steven D. Clouse, Jia Li The Arabidopsis thaliana Somatic Embryogenesis Receptor Kinases (SERKs) consist of five members, SERK1 to SERK5, of the leucine-rich repeat receptor-like kinase subfamily II (LRR-RLK II). SERK3 was named BRI1-Associated Receptor Kinase 1 (BAK1) due to its direct interaction with the brassinosteroid (BR) receptor BRI1 in vivo, while SERK4 has also been designated as BAK1-Like 1 (BKK1) for its functionally redundant role with BAK1. Here we provide genetic and biochemical evidence to demonstrate that SERKs are absolutely required for early steps in BR signaling. Overexpression of four of the five SERKs—SERK1, SERK2, SERK3/BAK1, and SERK4/BKK1—suppressed the phenotypes of an inte... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590807 Thu, 12 Jan 2012 05:00:00 +0100 5590807 Genomic Ancestry of North Africans Supports Back-to-Africa Migrations http://www.medworm.com/index.php?rid=5590806&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FgdBpnmJDWLQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002397 We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from “back-to-Africa” gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method ba... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590806 Thu, 12 Jan 2012 05:00:00 +0100 5590806 Cytoplasmic Polyadenylation Element Binding Protein Deficiency Stimulates PTEN and Stat3 mRNA Translation and Induces Hepatic Insulin Resistance http://www.medworm.com/index.php?rid=5590805&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fh091AJwZ7Ds%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002457 by Ilya M. Alexandrov, Maria Ivshina, Dae Young Jung, Randall Friedline, Hwi Jin Ko, Mei Xu, Bryan O'Sullivan-Murphy, Rita Bortell, Yen-Tsung Huang, Fumihiko Urano, Jason K. Kim, Joel D. Richter The cytoplasmic polyadenylation element binding protein CPEB1 (CPEB) regulates germ cell development, synaptic plasticity, and cellular senescence. A microarray analysis of mRNAs regulated by CPEB unexpectedly showed that several encoded proteins are involved in insulin signaling. An investigation of Cpeb1 knockout mice revealed that the expression of two particular negative regulators of insulin action, PTEN and Stat3, were aberrantly increased. Insulin signaling to Akt was attenuated in livers of CPEB–deficient mice, suggesting that they might be defective in regulating glucose homeostasis... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590805 Thu, 12 Jan 2012 05:00:00 +0100 5590805 Genome Engineering in Vibrio cholerae: A Feasible Approach to Address Biological Issues http://www.medworm.com/index.php?rid=5590804&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fd0wdvHVePdA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002472 by Marie-Eve Val, Ole Skovgaard, Magaly Ducos-Galand, Michael J. Bland, Didier Mazel Although bacteria with multipartite genomes are prevalent, our knowledge of the mechanisms maintaining their genome is very limited, and much remains to be learned about the structural and functional interrelationships of multiple chromosomes. Owing to its bi-chromosomal genome architecture and its importance in public health, Vibrio cholerae, the causative agent of cholera, has become a preferred model to study bacteria with multipartite genomes. However, most in vivo studies in V. cholerae have been hampered by its genome architecture, as it is difficult to give phenotypes to a specific chromosome. This difficulty was surmounted using a unique and powerful strategy based on massive rearrangement of ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590804 Thu, 12 Jan 2012 05:00:00 +0100 5590804 Calpains Mediate Integrin Attachment Complex Maintenance of Adult Muscle in Caenorhabditis elegans http://www.medworm.com/index.php?rid=5590803&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FYDLRCk5Vq-o%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002471 by Timothy Etheridge, Elizabeth A. Oczypok, Susann Lehmann, Brandon D. Fields, Freya Shephard, Lewis A. Jacobson, Nathaniel J. Szewczyk Two components of integrin containing attachment complexes, UNC-97/PINCH and UNC-112/MIG-2/Kindlin-2, were recently identified as negative regulators of muscle protein degradation and as having decreased mRNA levels in response to spaceflight. Integrin complexes transmit force between the inside and outside of muscle cells and signal changes in muscle size in response to force and, perhaps, disuse. We therefore investigated the effects of acute decreases in expression of the genes encoding these multi-protein complexes. We find that in fully developed adult Caenorhabditis elegans muscle, RNAi against genes encoding core, and peripheral, members of the... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590803 Thu, 12 Jan 2012 05:00:00 +0100 5590803 Adaptive Evolution of the Lactose Utilization Network in Experimentally Evolved Populations of Escherichia coli http://www.medworm.com/index.php?rid=5590802&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FYFwwEH24qaY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002444 by Selwyn Quan, J. Christian J. Ray, Zakari Kwota, Trang Duong, Gábor Balázsi, Tim F. Cooper, Russell D. Monds Adaptation to novel environments is often associated with changes in gene regulation. Nevertheless, few studies have been able both to identify the genetic basis of changes in regulation and to demonstrate why these changes are beneficial. To this end, we have focused on understanding both how and why the lactose utilization network has evolved in replicate populations of Escherichia coli. We found that lac operon regulation became strikingly variable, including changes in the mode of environmental response (bimodal, graded, and constitutive), sensitivity to inducer concentration, and maximum expression level. In addition, some classes of regulatory change were enriched in ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590802 Thu, 12 Jan 2012 05:00:00 +0100 5590802 A Gene Regulatory Network for Root Epidermis Cell Differentiation in Arabidopsis http://www.medworm.com/index.php?rid=5590801&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FcPufmGGY9A4%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002446 by Angela Bruex, Raghunandan M. Kainkaryam, Yana Wieckowski, Yeon Hee Kang, Christine Bernhardt, Yang Xia, Xiaohua Zheng, Jean Y. Wang, Myeong Min Lee, Philip Benfey, Peter J. Woolf, John Schiefelbein The root epidermis of Arabidopsis provides an exceptional model for studying the molecular basis of cell fate and differentiation. To obtain a systems-level view of root epidermal cell differentiation, we used a genome-wide transcriptome approach to define and organize a large set of genes into a transcriptional regulatory network. Using cell fate mutants that produce only one of the two epidermal cell types, together with fluorescence-activated cell-sorting to preferentially analyze the root epidermis transcriptome, we identified 1,582 genes differentially expressed in the root-hair or ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590801 Thu, 12 Jan 2012 05:00:00 +0100 5590801 A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies http://www.medworm.com/index.php?rid=5590800&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FYOCPAHzQmok%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002451 by Molly E. McCue, Danika L. Bannasch, Jessica L. Petersen, Jessica Gurr, Ernie Bailey, Matthew M. Binns, Ottmar Distl, Gérard Guérin, Telhisa Hasegawa, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, M. Cecilia T. Penedo, Knut H. Røed, Oliver A. Ryder, June E. Swinburne, Teruaki Tozaki, Stephanie J. Valberg, Mark Vaudin, Kerstin Lindblad-Toh, Claire M. Wade, James R. Mickelson An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species. More than 54,000 polymorphic SNPs provided an average inter-SNP spacing of ∼43 kb. The mean minor allele frequency across domestic horse breeds was 0.23, and the number of polymorphic SNPs within breeds ranged from 43,287 to 52,085. Genome-wide link... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590800 Thu, 12 Jan 2012 05:00:00 +0100 5590800 An siRNA Screen in Pancreatic Beta Cells Reveals a Role for Gpr27 in Insulin Production http://www.medworm.com/index.php?rid=5590799&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FkfLSKaIRrNA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002449 by Gregory M. Ku, Zachary Pappalardo, Chun Chieh Luo, Michael S. German, Michael T. McManus The prevalence of type 2 diabetes in the United States is projected to double or triple by 2050. We reasoned that the genes that modulate insulin production might be new targets for diabetes therapeutics. Therefore, we developed an siRNA screening system to identify genes important for the activity of the insulin promoter in beta cells. We created a subclone of the MIN6 mouse pancreatic beta cell line that expresses destabilized GFP under the control of a 362 base pair fragment of the human insulin promoter and the mCherry red fluorescent protein under the control of the constitutively active rous sarcoma virus promoter. The ratio of the GFP to mCherry fluorescence of a cell indicates its insul... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590799 Thu, 12 Jan 2012 05:00:00 +0100 5590799 The Drosophila melanogaster Seminal Fluid Protease “Seminase” Regulates Proteolytic and Post-Mating Reproductive Processes http://www.medworm.com/index.php?rid=5590798&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F-qyviwiY_m8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002435 by Brooke A. LaFlamme, K. Ravi Ram, Mariana F. Wolfner Proteases and protease inhibitors have been identified in the ejaculates of animal taxa ranging from invertebrates to mammals and form a major protein class among Drosophila melanogaster seminal fluid proteins (SFPs). Other than a single protease cascade in mammals that regulates seminal clot liquefaction, no proteolytic cascades (i.e. pathways with at least two proteases acting in sequence) have been identified in seminal fluids. In Drosophila, SFPs are transferred to females during mating and, together with sperm, are necessary for the many post-mating responses elicited in females. Though several SFPs are proteolytically cleaved either during or after mating, virtually nothing is known about the proteases involved in these clea... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5590798 Thu, 12 Jan 2012 05:00:00 +0100 5590798 Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli http://www.medworm.com/index.php?rid=5567019&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FtTBvdgaOcxw%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002442 by Ernest K. Boamah, Elena Kotova, Mikael Garabedian, Michael Jarnik, Alexei V. Tulin Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberran... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5567019 Thu, 05 Jan 2012 05:00:00 +0100 5567019 Functional Specialization of the Plant miR396 Regulatory Network through Distinct MicroRNA–Target Interactions http://www.medworm.com/index.php?rid=5567018&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fp_Evow4qWiM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002419 by Juan M. Debernardi, Ramiro E. Rodriguez, Martin A. Mecchia, Javier F. Palatnik MicroRNAs (miRNAs) are ∼21 nt small RNAs that regulate gene expression in animals and plants. They can be grouped into families comprising different genes encoding similar or identical mature miRNAs. Several miRNA families are deeply conserved in plant lineages and regulate key aspects of plant development, hormone signaling, and stress response. The ancient miRNA miR396 regulates conserved targets belonging to the GROWTH-REGULATING FACTOR (GRF) family of transcription factors, which are known to control cell proliferation in Arabidopsis leaves. In this work, we characterized the regulation of an additional target for miR396, the transcription factor bHLH74, that is necessary for Arabidopsis normal dev... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5567018 Thu, 05 Jan 2012 05:00:00 +0100 5567018 Genome-Wide Assessment of AU-Rich Elements by the AREScore Algorithm http://www.medworm.com/index.php?rid=5567017&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FpVuK60n57AE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002433 by Milan Spasic, Caroline C. Friedel, Johanna Schott, Jochen Kreth, Kathrin Leppek, Sarah Hofmann, Sevim Ozgur, Georg Stoecklin In mammalian cells, AU-rich elements (AREs) are well known regulatory sequences located in the 3′ untranslated region (UTR) of many short-lived mRNAs. AREs cause mRNAs to be degraded rapidly and thereby suppress gene expression at the posttranscriptional level. Based on the number of AUUUA pentamers, their proximity, and surrounding AU-rich regions, we generated an algorithm termed AREScore that identifies AREs and provides a numerical assessment of their strength. By analyzing the AREScore distribution in the transcriptomes of 14 metazoan species, we provide evidence that AREs were selected for in several vertebrates and Drosophila melanogaster. We then me... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5567017 Thu, 05 Jan 2012 05:00:00 +0100 5567017 The Yeast Complex I Equivalent NADH Dehydrogenase Rescues pink1 Mutants http://www.medworm.com/index.php?rid=5567016&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FZC8Zjk8a59M%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002456 by Sven Vilain, Giovanni Esposito, Dominik Haddad, Onno Schaap, Mariya P. Dobreva, Melissa Vos, Stefanie Van Meensel, Vanessa A. Morais, Bart De Strooper, Patrik Verstreken Pink1 is a mitochondrial kinase involved in Parkinson's disease, and loss of Pink1 function affects mitochondrial morphology via a pathway involving Parkin and components of the mitochondrial remodeling machinery. Pink1 loss also affects the enzymatic activity of isolated Complex I of the electron transport chain (ETC); however, the primary defect in pink1 mutants is unclear. We tested the hypothesis that ETC deficiency is upstream of other pink1-associated phenotypes. We expressed Saccaromyces cerevisiae Ndi1p, an enzyme that bypasses ETC Complex I, or sea squirt Ciona intestinalis AOX, an enzyme that bypasses ETC... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5567016 Thu, 05 Jan 2012 05:00:00 +0100 5567016 Checkpoints in a Yeast Differentiation Pathway Coordinate Signaling during Hyperosmotic Stress http://www.medworm.com/index.php?rid=5567015&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F_qiYBKEwRug%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002437 by Michal J. Nagiec, Henrik G. Dohlman All eukaryotes have the ability to detect and respond to environmental and hormonal signals. In many cases these signals evoke cellular changes that are incompatible and must therefore be orchestrated by the responding cell. In the yeast Saccharomyces cerevisiae, hyperosmotic stress and mating pheromones initiate signaling cascades that each terminate with a MAP kinase, Hog1 and Fus3, respectively. Despite sharing components, these pathways are initiated by distinct inputs and produce distinct cellular behaviors. To understand how these responses are coordinated, we monitored the pheromone response during hyperosmotic conditions. We show that hyperosmotic stress limits pheromone signaling in at least three ways. First, stress delays the expressio... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5567015 Thu, 05 Jan 2012 05:00:00 +0100 5567015 Contribution of Intragenic DNA Methylation in Mouse Gametic DNA Methylomes to Establish Oocyte-Specific Heritable Marks http://www.medworm.com/index.php?rid=5567014&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FBzu_6VwoYJk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002440 by Hisato Kobayashi, Takayuki Sakurai, Misaki Imai, Nozomi Takahashi, Atsushi Fukuda, Obata Yayoi, Shun Sato, Kazuhiko Nakabayashi, Kenichiro Hata, Yusuke Sotomaru, Yutaka Suzuki, Tomohiro Kono Genome-wide dynamic changes in DNA methylation are indispensable for germline development and genomic imprinting in mammals. Here, we report single-base resolution DNA methylome and transcriptome maps of mouse germ cells, generated using whole-genome shotgun bisulfite sequencing and cDNA sequencing (mRNA-seq). Oocyte genomes showed a significant positive correlation between mRNA transcript levels and methylation of the transcribed region. Sperm genomes had nearly complete coverage of methylation, except in the CpG-rich regions, and showed a significant negative correlation between gene expressi... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5567014 Thu, 05 Jan 2012 05:00:00 +0100 5567014 Microenvironmental Regulation by Fibrillin-1 http://www.medworm.com/index.php?rid=5567013&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FxG2eN8kRV-w%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002425 by Gerhard Sengle, Ko Tsutsui, Douglas R. Keene, Sara F. Tufa, Eric J. Carlson, Noe L. Charbonneau, Robert N. Ono, Takako Sasaki, Mary K. Wirtz, John R. Samples, Liselotte I. Fessler, John H. Fessler, Kiyotoshi Sekiguchi, Susan J. Hayflick, Lynn Y. Sakai Fibrillin-1 is a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes. A role for fibrillin-1 in specifying tissue microenvironments has not been elucidated, even though the concept that fibrillin-1 provides extracellular control of growth factor signaling is currently appreciated. Mutations in FBN1 are mainly responsible for the Marfan syndrome (MFS), recognized by its pleiotropic clinical features including tall stature and arachnodactyly, aortic dilatation and dissection, and ectopia lentis. Each ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5567013 Thu, 05 Jan 2012 05:00:00 +0100 5567013 Duox, Flotillin-2, and Src42A Are Required to Activate or Delimit the Spread of the Transcriptional Response to Epidermal Wounds in Drosophila http://www.medworm.com/index.php?rid=5556110&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fvq-79ksXPqM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002424 by Michelle T. Juarez, Rachel A. Patterson, Efren Sandoval-Guillen, William McGinnis The epidermis is the largest organ of the body for most animals, and the first line of defense against invading pathogens. A breach in the epidermal cell layer triggers a variety of localized responses that in favorable circumstances result in the repair of the wound. Many cellular and genetic responses must be limited to epidermal cells that are close to wounds, but how this is regulated is still poorly understood. The order and hierarchy of epidermal wound signaling factors are also still obscure. The Drosophila embryonic epidermis provides an excellent system to study genes that regulate wound healing processes. We have developed a variety of fluorescent reporters that provide a visible readout of ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556110 Thu, 29 Dec 2011 05:00:00 +0100 5556110 DNA Methylation of the Gonadal Aromatase (cyp19a) Promoter Is Involved in Temperature-Dependent Sex Ratio Shifts in the European Sea Bass http://www.medworm.com/index.php?rid=5556109&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FtNzGtYzrN1w%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002447 by Laia Navarro-Martín, Jordi Viñas, Laia Ribas, Noelia Díaz, Arantxa Gutiérrez, Luciano Di Croce, Francesc Piferrer Sex ratio shifts in response to temperature are common in fish and reptiles. However, the mechanism linking temperature during early development and sex ratios has remained elusive. We show in the European sea bass (sb), a fish in which temperature effects on sex ratios are maximal before the gonads form, that juvenile males have double the DNA methylation levels of females in the promoter of gonadal aromatase (cyp19a), the enzyme that converts androgens into estrogens. Exposure to high temperature increased the cyp19a promoter methylation levels of females, indicating that induced-masculinization involves DNA methylation-mediated control of aromatase gene expressio... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556109 Thu, 29 Dec 2011 05:00:00 +0100 5556109 Common Variants Show Predicted Polygenic Effects on Height in the Tails of the Distribution, Except in Extremely Short Individuals http://www.medworm.com/index.php?rid=5556108&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FizC0vH8PpOk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002439 by Yingleong Chan, Oddgeir L. Holmen, Andrew Dauber, Lars Vatten, Aki S. Havulinna, Frank Skorpen, Kirsti Kvaløy, Kaisa Silander, Thutrang T. Nguyen, Cristen Willer, Michael Boehnke, Markus Perola, Aarno Palotie, Veikko Salomaa, Kristian Hveem, Timothy M. Frayling, Joel N. Hirschhorn, Michael N. Weedon Common genetic variants have been shown to explain a fraction of the inherited variation for many common diseases and quantitative traits, including height, a classic polygenic trait. The extent to which common variation determines the phenotype of highly heritable traits such as height is uncertain, as is the extent to which common variation is relevant to individuals with more extreme phenotypes. To address these questions, we studied 1,214 individuals from the top and bottom extreme... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556108 Thu, 29 Dec 2011 05:00:00 +0100 5556108 The RNA Silencing Enzyme RNA Polymerase V Is Required for Plant Immunity http://www.medworm.com/index.php?rid=5556107&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FMGuigmOVfmM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002434 by Ana López, Vicente Ramírez, Javier García-Andrade, Victor Flors, Pablo Vera RNA–directed DNA methylation (RdDM) is an epigenetic control mechanism driven by small interfering RNAs (siRNAs) that influence gene function. In plants, little is known of the involvement of the RdDM pathway in regulating traits related to immune responses. In a genetic screen designed to reveal factors regulating immunity in Arabidopsis thaliana, we identified NRPD2 as the OVEREXPRESSOR OF CATIONIC PEROXIDASE 1 (OCP1). NRPD2 encodes the second largest subunit of the plant-specific RNA Polymerases IV and V (Pol IV and Pol V), which are crucial for the RdDM pathway. The ocp1 and nrpd2 mutants showed increases in disease susceptibility when confronted with the necrotrophic fungal pathogens Botrytis cine... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556107 Thu, 29 Dec 2011 05:00:00 +0100 5556107 Transcription Is Required to Establish Maternal Imprinting at the Prader-Willi Syndrome and Angelman Syndrome Locus http://www.medworm.com/index.php?rid=5556106&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FSlHHNm1rGE8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002422 by Emily Y. Smith, Christopher R. Futtner, Stormy J. Chamberlain, Karen A. Johnstone, James L. Resnick The Prader-Willi syndrome (PWS [MIM 17620]) and Angelman syndrome (AS [MIM 105830]) locus is controlled by a bipartite imprinting center (IC) consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal allele, while the AS-IC acts to epigenetically inactivate the PWS-IC on the maternal allele, thus silencing the paternally expressed genes. Gene order and imprinting patterns at the PWS/AS locus are well conserved from human to mouse; however, a murine AS-IC has yet to be identified. We investigated a potential regulatory role for transcription from the Snrpn alternative upstream exons in sil... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556106 Thu, 29 Dec 2011 05:00:00 +0100 5556106 MAPK/ERK Signaling Regulates Insulin Sensitivity to Control Glucose Metabolism in Drosophila http://www.medworm.com/index.php?rid=5556105&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FlQk_Eb-CsoQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002429 by Wei Zhang, Barry J. Thompson, Ville Hietakangas, Stephen M. Cohen The insulin/IGF-activated AKT signaling pathway plays a crucial role in regulating tissue growth and metabolism in multicellular animals. Although core components of the pathway are well defined, less is known about mechanisms that adjust the sensitivity of the pathway to extracellular stimuli. In humans, disturbance in insulin sensitivity leads to impaired clearance of glucose from the blood stream, which is a hallmark of diabetes. Here we present the results of a genetic screen in Drosophila designed to identify regulators of insulin sensitivity in vivo. Components of the MAPK/ERK pathway were identified as modifiers of cellular insulin responsiveness. Insulin resistance was due to downregulation of insulin-like re... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556105 Thu, 29 Dec 2011 05:00:00 +0100 5556105 Autosomal Recessive Dilated Cardiomyopathy due to DOLK Mutations Results from Abnormal Dystroglycan O-Mannosylation http://www.medworm.com/index.php?rid=5556104&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FHlGzsrA0MHQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002427 by Dirk J. Lefeber, Arjan P. M. de Brouwer, Eva Morava, Moniek Riemersma, Janneke H. M. Schuurs-Hoeijmakers, Birgit Absmanner, Kiek Verrijp, Willem M. R. van den Akker, Karin Huijben, Gerry Steenbergen, Jeroen van Reeuwijk, Adam Jozwiak, Nili Zucker, Avraham Lorber, Martin Lammens, Carlos Knopf, Hans van Bokhoven, Stephanie Grünewald, Ludwig Lehle, Livia Kapusta, Hanna Mandel, Ron A. Wevers Genetic causes for autosomal recessive forms of dilated cardiomyopathy (DCM) are only rarely identified, although they are thought to contribute considerably to sudden cardiac death and heart failure, especially in young children. Here, we describe 11 young patients (5–13 years) with a predominant presentation of dilated cardiomyopathy (DCM). Metabolic investigations showed deficient protein N-g... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556104 Thu, 29 Dec 2011 05:00:00 +0100 5556104 The Connection between Space and Thinking: An Interview with Rafael Viñoly http://www.medworm.com/index.php?rid=5556103&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FRTgbrk3ABxU%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002445 by Jane Gitschier (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556103 Thu, 29 Dec 2011 05:00:00 +0100 5556103 Substitutions in the Amino-Terminal Tail of Neurospora Histone H3 Have Varied Effects on DNA Methylation http://www.medworm.com/index.php?rid=5556102&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FCjzbfiu9c6s%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002423 by Keyur K. Adhvaryu, Emanuela Berge, Hisashi Tamaru, Michael Freitag, Eric U. Selker Eukaryotic genomes are partitioned into active and inactive domains called euchromatin and heterochromatin, respectively. In Neurospora crassa, heterochromatin formation requires methylation of histone H3 at lysine 9 (H3K9) by the SET domain protein DIM-5. Heterochromatin protein 1 (HP1) reads this mark and directly recruits the DNA methyltransferase, DIM-2. An ectopic H3 gene carrying a substitution at K9 (hH3K9L or hH3K9R) causes global loss of DNA methylation in the presence of wild-type hH3 (hH3WT). We investigated whether other residues in the N-terminal tail of H3 are important for methylation of DNA and of H3K9. Mutations in the N-terminal tail of H3 were generated and tested for effects in vi... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556102 Thu, 29 Dec 2011 05:00:00 +0100 5556102 The Caenorhabditis elegans Synthetic Multivulva Genes Prevent Ras Pathway Activation by Tightly Repressing Global Ectopic Expression of lin-3 EGF http://www.medworm.com/index.php?rid=5556101&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FHm2x9Oy2DiM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002418 by Adam M. Saffer, Dong Hyun Kim, Alexander van Oudenaarden, H. Robert Horvitz The Caenorhabditis elegans class A and B synthetic multivulva (synMuv) genes redundantly antagonize an EGF/Ras pathway to prevent ectopic vulval induction. We identify a class A synMuv mutation in the promoter of the lin-3 EGF gene, establishing that lin-3 is the key biological target of the class A synMuv genes in vulval development and that the repressive activities of the class A and B synMuv pathways are integrated at the level of lin-3 expression. Using FISH with single mRNA molecule resolution, we find that lin-3 EGF expression is tightly restricted to only a few tissues in wild-type animals, including the germline. In synMuv double mutants, lin-3 EGF is ectopically expressed at low levels throughout ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556101 Thu, 29 Dec 2011 05:00:00 +0100 5556101 A Genetic Screening Strategy Identifies Novel Regulators of the Proteostasis Network http://www.medworm.com/index.php?rid=5556100&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F3S26ulBIV6Q%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002438 In this study, we have identified new components of the proteostasis network that can suppress aggregation and proteotoxicity, by performing RNA interference (RNAi) genetic screens for multiple unrelated conformationally challenged cytoplasmic proteins expressed in Caenorhabditis elegans. We identified 88 suppressors of polyglutamine (polyQ) aggregation, of which 63 modifiers also suppressed aggregation of mutant SOD1G93A. Of these, only 23 gene-modifiers suppressed aggregation and restored animal motility, revealing that aggregation and toxicity can be genetically uncoupled. Nine of these modifiers were shown to be effective in restoring the folding and function of multiple endogenous temperature-sensitive (TS) mutant proteins, of which five improved folding in a HSF-1–dependent manner,... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556100 Thu, 29 Dec 2011 05:00:00 +0100 5556100 Interspecific Sex in Grass Smuts and the Genetic Diversity of Their Pheromone-Receptor System http://www.medworm.com/index.php?rid=5556099&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fh5z8XWC8428%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002436 by Ronny Kellner, Evelyn Vollmeister, Michael Feldbrügge, Dominik Begerow The grass smuts comprise a speciose group of biotrophic plant parasites, so-called Ustilaginaceae, which are specifically adapted to hosts of sweet grasses, the Poaceae family. Mating takes a central role in their life cycle, as it initiates parasitism by a morphological and physiological transition from saprobic yeast cells to pathogenic filaments. As in other fungi, sexual identity is determined by specific genomic regions encoding allelic variants of a pheromone-receptor (PR) system and heterodimerising transcription factors. Both operate in a biphasic mating process that starts with PR–triggered recognition, directed growth of conjugation hyphae, and plasmogamy of compatible mating partners. So far, studi... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5556099 Thu, 29 Dec 2011 05:00:00 +0100 5556099 Azospirillum Genomes Reveal Transition of Bacteria from Aquatic to Terrestrial Environments http://www.medworm.com/index.php?rid=5531238&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FBHp4cm4m6Jg%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002430 by Florence Wisniewski-Dyé, Kirill Borziak, Gurusahai Khalsa-Moyers, Gladys Alexandre, Leonid O. Sukharnikov, Kristin Wuichet, Gregory B. Hurst, W. Hayes McDonald, Jon S. Robertson, Valérie Barbe, Alexandra Calteau, Zoé Rouy, Sophie Mangenot, Claire Prigent-Combaret, Philippe Normand, Mickaël Boyer, Patricia Siguier, Yves Dessaux, Claudine Elmerich, Guy Condemine, Ganisan Krishnen, Ivan Kennedy, Andrew H. Paterson, Victor González, Patrick Mavingui, Igor B. Zhulin Fossil records indicate that life appeared in marine environments ∼3.5 billion years ago (Gyr) and transitioned to terrestrial ecosystems nearly 2.5 Gyr. Sequence analysis suggests that “hydrobacteria” and “terrabacteria” might have diverged as early as 3 Gyr. Bacteria of the genus Azospirillum are associated ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5531238 Thu, 22 Dec 2011 05:00:00 +0100 5531238 Ror2 Enhances Polarity and Directional Migration of Primordial Germ Cells http://www.medworm.com/index.php?rid=5531237&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FxqZNcmqNdk0%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002428 by Diana J. Laird, Svetlana Altshuler-Keylin, Michael D. Kissner, Xin Zhou, Kathryn V. Anderson The trafficking of primordial germ cells (PGCs) across multiple embryonic structures to the nascent gonads ensures the transmission of genetic information to the next generation through the gametes, yet our understanding of the mechanisms underlying PGC migration remains incomplete. Here we identify a role for the receptor tyrosine kinase-like protein Ror2 in PGC development. In a Ror2 mouse mutant we isolated in a genetic screen, PGC migration and survival are dysregulated, resulting in a diminished number of PGCs in the embryonic gonad. A similar phenotype in Wnt5a mutants suggests that Wnt5a acts as a ligand to Ror2 in PGCs, although we do not find evidence that WNT5A functions as a PGC ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5531237 Thu, 22 Dec 2011 05:00:00 +0100 5531237 Histone H3K9 Trimethylase Eggless Controls Germline Stem Cell Maintenance and Differentiation http://www.medworm.com/index.php?rid=5531236&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FHEMn4MiVYs8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002426 In this study, we show that Eggless (Egg), a H3K9 methyltransferase in Drosophila, is required in GSCs for controlling self-renewal and in escort cells for regulating germ cell differentiation. egg mutant ovaries primarily exhibit germ cell differentiation defects in young females and gradually lose GSCs with time, indicating that Egg regulates both germ cell maintenance and differentiation. Marked mutant egg GSCs lack expression of trimethylated H3K9 (H3k9me3) and are rapidly lost from the niche, but their mutant progeny can still differentiate into 16-cell cysts, indicating that Egg is required intrinsically to control GSC self-renewal but not differentiation. Interestingly, BMP-mediated transcriptional repression of differentiation factor bam in marked egg mutant GSCs remains normal, in... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5531236 Thu, 22 Dec 2011 05:00:00 +0100 5531236 Candidate Gene Screen in the Red Flour Beetle Tribolium Reveals Six3 as Ancient Regulator of Anterior Median Head and Central Complex Development http://www.medworm.com/index.php?rid=5531235&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FmX-HlOwkWuc%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002416 by Nico Posnien, Nikolaus Dieter Bernhard Koniszewski, Hendrikje Jeannette Hein, Gregor Bucher Several highly conserved genes play a role in anterior neural plate patterning of vertebrates and in head and brain patterning of insects. However, head involution in Drosophila has impeded a systematic identification of genes required for insect head formation. Therefore, we use the red flour beetle Tribolium castaneum in order to comprehensively test the function of orthologs of vertebrate neural plate patterning genes for a function in insect head development. RNAi analysis reveals that most of these genes are indeed required for insect head capsule patterning, and we also identified several genes that had not been implicated in this process before. Furthermore, we show that Tc-six3/optix... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5531235 Thu, 22 Dec 2011 05:00:00 +0100 5531235 A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken http://www.medworm.com/index.php?rid=5531234&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FUCawfmZeGuQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002412 by Ben Dorshorst, Anna-Maja Molin, Carl-Johan Rubin, Anna M. Johansson, Lina Strömstedt, Manh-Hung Pham, Chih-Feng Chen, Finn Hallböök, Chris Ashwell, Leif Andersson Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicat... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5531234 Thu, 22 Dec 2011 05:00:00 +0100 5531234 Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1 http://www.medworm.com/index.php?rid=5531233&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FU92caRvPhXg%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002404 by You-Ying Chau, David Brownstein, Heidi Mjoseng, Wen-Chin Lee, Natalija Buza-Vidas, Claus Nerlov, Sten Eirik Jacobsen, Paul Perry, Rachel Berry, Anna Thornburn, David Sexton, Nik Morton, Peter Hohenstein, Elisabeth Freyer, Kay Samuel, Rob van't Hof, Nicholas Hastie There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal–epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors. Although Wt1 is only expressed in rare cell... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5531233 Thu, 22 Dec 2011 05:00:00 +0100 5531233 A High-Resolution Whole-Genome Map of Key Chromatin Modifications in the Adult Drosophila melanogaster http://www.medworm.com/index.php?rid=5510610&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FSMtdUkStShg%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002380 by Hang Yin, Sarah Sweeney, Debasish Raha, Michael Snyder, Haifan Lin Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism. Here, we report a modified method for chromatin immunoprecipitation and deep sequencing (ChIP–Seq) and its use to construct a high-resolution map of the Drosophila melanogaster key histone marks, heterochromatin protein 1a (HP1a) and RNA polymerase II (polII). These factors are mapped at 50-bp resolution genome-wide and at 5-bp resolution for regulatory sequences of genes, which reveals fundamental features of chromatin modification landscape shared by major adult Drosophila cell types: the enrichment of both heterochromatic and euchro... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510610 Thu, 15 Dec 2011 05:00:00 +0100 5510610 An Anti-Checkpoint Activity for Rif1 http://www.medworm.com/index.php?rid=5510609&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F7bo49vQFqTE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002421 by Yaniv Harari, Linda Rubinstein, Martin Kupiec (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510609 Thu, 15 Dec 2011 05:00:00 +0100 5510609 A Functional Phylogenomic View of the Seed Plants http://www.medworm.com/index.php?rid=5510608&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FvfoEXYfyxMA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002411 by Ernest K. Lee, Angelica Cibrian-Jaramillo, Sergios-Orestis Kolokotronis, Manpreet S. Katari, Alexandros Stamatakis, Michael Ott, Joanna C. Chiu, Damon P. Little, Dennis Wm. Stevenson, W. Richard McCombie, Robert A. Martienssen, Gloria Coruzzi, Rob DeSalle A novel result of the current research is the development and implementation of a unique functional phylogenomic approach that explores the genomic origins of seed plant diversification. We first use 22,833 sets of orthologs from the nuclear genomes of 101 genera across land plants to reconstruct their phylogenetic relationships. One of the more salient results is the resolution of some enigmatic relationships in seed plant phylogeny, such as the placement of Gnetales as sister to the rest of the gymnosperms. In using this novel p... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510608 Thu, 15 Dec 2011 05:00:00 +0100 5510608 Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains http://www.medworm.com/index.php?rid=5510607&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FMon8_AFGrRo%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002409 by Nicolas Siaud, Maria A. Barbera, Akinori Egashira, Isabel Lam, Nicole Christ, Katharina Schlacher, Bing Xia, Maria Jasin The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with th... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510607 Thu, 15 Dec 2011 05:00:00 +0100 5510607 HIF-1 Regulates Iron Homeostasis in Caenorhabditis elegans by Activation and Inhibition of Genes Involved in Iron Uptake and Storage http://www.medworm.com/index.php?rid=5510606&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FJAW-RhoGrMs%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002394 by Steven Joshua Romney, Ben S. Newman, Colin Thacker, Elizabeth A. Leibold Caenorhabditis elegans ftn-1 and ftn-2, which encode the iron-storage protein ferritin, are transcriptionally inhibited during iron deficiency in intestine. Intestinal specific transcription is dependent on binding of ELT-2 to GATA binding sites in an iron-dependent enhancer (IDE) located in ftn-1 and ftn-2 promoters, but the mechanism for iron regulation is unknown. Here, we identify HIF-1 (hypoxia-inducible factor -1) as a negative regulator of ferritin transcription. HIF-1 binds to hypoxia-response elements (HREs) in the IDE in vitro and in vivo. Depletion of hif-1 by RNA interference blocks transcriptional inhibition of ftn-1 and ftn-2 reporters, and ftn-1 and ftn-2 mRNAs are not regulated in a hif-1 null ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510606 Thu, 15 Dec 2011 05:00:00 +0100 5510606 Identification of Evolutionarily Conserved Exons as Regulated Targets for the Splicing Activator Tra2β in Development http://www.medworm.com/index.php?rid=5510605&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FHnRxMsr_ZRs%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002390 by Sushma Grellscheid, Caroline Dalgliesh, Markus Storbeck, Andrew Best, Yilei Liu, Miriam Jakubik, Ylva Mende, Ingrid Ehrmann, Tomaz Curk, Kristina Rossbach, Cyril F. Bourgeois, James Stévenin, David Grellscheid, Michael S. Jackson, Brunhilde Wirth, David J. Elliott Alternative splicing amplifies the information content of the genome, creating multiple mRNA isoforms from single genes. The evolutionarily conserved splicing activator Tra2β (Sfrs10) is essential for mouse embryogenesis and implicated in spermatogenesis. Here we find that Tra2β is up-regulated as the mitotic stem cell containing population of male germ cells differentiate into meiotic and post-meiotic cells. Using CLIP coupled to deep sequencing, we found that Tra2β binds a high frequency of exons and identified spec... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510605 Thu, 15 Dec 2011 05:00:00 +0100 5510605 Drosophila Ribosomal Protein Mutants Control Tissue Growth Non-Autonomously via Effects on the Prothoracic Gland and Ecdysone http://www.medworm.com/index.php?rid=5510604&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FsjSHupnkVxo%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002408 by Jane I. Lin, Naomi C. Mitchell, Marina Kalcina, Elly Tchoubrieva, Mary J. Stewart, Steven J. Marygold, Cherryl D. Walker, George Thomas, Sally J. Leevers, Richard B. Pearson, Leonie M. Quinn, Ross D. Hannan The ribosome is critical for all aspects of cell growth due to its essential role in protein synthesis. Paradoxically, many Ribosomal proteins (Rps) act as tumour suppressors in Drosophila and vertebrates. To examine how reductions in Rps could lead to tissue overgrowth, we took advantage of the observation that an RpS6 mutant dominantly suppresses the small rough eye phenotype in a cyclin E hypomorphic mutant (cycEJP). We demonstrated that the suppression of cycEJP by the RpS6 mutant is not a consequence of restoring CycE protein levels or activity in the eye imaginal tissue. R... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510604 Thu, 15 Dec 2011 05:00:00 +0100 5510604 A Novel Checkpoint and RPA Inhibitory Pathway Regulated by Rif1 http://www.medworm.com/index.php?rid=5510603&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FdEHxjjHqCK4%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002417 by Yuan Xue, Michael D. Rushton, Laura Maringele Cells accumulate single-stranded DNA (ssDNA) when telomere capping, DNA replication, or DNA repair is impeded. This accumulation leads to cell cycle arrest through activating the DNA–damage checkpoints involved in cancer protection. Hence, ssDNA accumulation could be an anti-cancer mechanism. However, ssDNA has to accumulate above a certain threshold to activate checkpoints. What determines this checkpoint-activation threshold is an important, yet unanswered question. Here we identify Rif1 (Rap1-Interacting Factor 1) as a threshold-setter. Following telomere uncapping, we show that budding yeast Rif1 has unprecedented effects for a protein, inhibiting the recruitment of checkpoint proteins and RPA (Replication Protein A) to damaged ch... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510603 Thu, 15 Dec 2011 05:00:00 +0100 5510603 A Densely Interconnected Genome-Wide Network of MicroRNAs and Oncogenic Pathways Revealed Using Gene Expression Signatures http://www.medworm.com/index.php?rid=5510602&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fi8fWw8AwPpk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002415 by Chia Huey Ooi, Hue Kian Oh, Hannah Zhu'Ai Wang, Angie Lay Keng Tan, Jeanie Wu, Minghui Lee, Sun Young Rha, Hyun Cheol Chung, David Marc Virshup, Patrick Tan MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping >300 gene expression signatures to >700 primary tumor profiles, we constructed a genome-wide miRNA–pathway network predictin... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510602 Thu, 15 Dec 2011 05:00:00 +0100 5510602 Target Site Recognition by a Diversity-Generating Retroelement http://www.medworm.com/index.php?rid=5510601&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fik6UIpEHtxU%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002414 by Huatao Guo, Longping V. Tse, Angela W. Nieh, Elizabeth Czornyj, Steven Williams, Sabrina Oukil, Vincent B. Liu, Jeff F. Miller Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype, we have characterized requirements for DGR target site function. Although sequences upstream of VR are dispensable, a 24 bp sequence immediately downstream of VR, whi... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510601 Thu, 15 Dec 2011 05:00:00 +0100 5510601 Ancestral Components of Admixed Genomes in a Mexican Cohort http://www.medworm.com/index.php?rid=5510600&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FRscYssE2_Y0%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002410 by Nicholas A. Johnson, Marc A. Coram, Mark D. Shriver, Isabelle Romieu, Gregory S. Barsh, Stephanie J. London, Hua Tang For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with r... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5510600 Thu, 15 Dec 2011 05:00:00 +0100 5510600 The FGFR4-G388R Polymorphism Promotes Mitochondrial STAT3 Serine Phosphorylation to Facilitate Pituitary Growth Hormone Cell Tumorigenesis http://www.medworm.com/index.php?rid=5491450&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FyQnnflNXljA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002400 by Toru Tateno, Sylvia L. Asa, Lei Zheng, Thomas Mayr, Axel Ullrich, Shereen Ezzat Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relie... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5491450 Thu, 08 Dec 2011 05:00:00 +0100 5491450 An Assessment of the Individual and Collective Effects of Variants on Height Using Twins and a Developmentally Informative Study Design http://www.medworm.com/index.php?rid=5491449&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FaGwkcVBWUmk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002413 by Scott I. Vrieze, Matt McGue, Michael B. Miller, Lisa N. Legrand, Nicholas J. Schork, William G. Iacono In a sample of 3,187 twins and 3,294 of their parents, we sought to investigate association of both individual variants and a genotype-based height score involving 176 of the 180 common genetic variants with adult height identified recently by the GIANT consortium. First, longitudinal observations on height spanning pre-adolescence through adulthood in the twin sample allowed us to investigate the separate effects of the previously identified SNPs on pre-pubertal height and pubertal growth spurt. We show that the effect of SNPs identified by the GIANT consortium is primarily on prepubertal height. Only one SNP, rs7759938 in LIN28B, approached a significant association with puberta... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5491449 Thu, 08 Dec 2011 05:00:00 +0100 5491449 Age-Related Neuronal Degeneration: Complementary Roles of Nucleotide Excision Repair and Transcription-Coupled Repair in Preventing Neuropathology http://www.medworm.com/index.php?rid=5491448&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fg1nEYsBb1u0%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002405 by Dick Jaarsma, Ingrid van der Pluijm, Monique C. de Waard, Elize D. Haasdijk, Renata Brandt, Marcel Vermeij, Yvonne Rijksen, Alex Maas, Harry van Steeg, Jan H. J. Hoeijmakers, Gijsbertus T. J. van der Horst Neuronal degeneration is a hallmark of many DNA repair syndromes. Yet, how DNA damage causes neuronal degeneration and whether defects in different repair systems affect the brain differently is largely unknown. Here, we performed a systematic detailed analysis of neurodegenerative changes in mouse models deficient in nucleotide excision repair (NER) and transcription-coupled repair (TCR), two partially overlapping DNA repair systems that remove helix-distorting and transcription-blocking lesions, respectively, and that are associated with the UV-sensitive syndromes xeroderma pig... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5491448 Thu, 08 Dec 2011 05:00:00 +0100 5491448 A Comprehensive Analysis of Shared Loci between Systemic Lupus Erythematosus (SLE) and Sixteen Autoimmune Diseases Reveals Limited Genetic Overlap http://www.medworm.com/index.php?rid=5491447&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FrvU9kJS-LCY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002406 This study represents the most comprehensive evaluation of shared autoimmune loci to date, supports a relatively distinct non–MHC genetic susceptibility for SLE, provides further evidence for previously and newly identified shared genes in SLE, and highlights the value of studies of potentially pleiotropic genes in autoimmune diseases. (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5491447 Thu, 08 Dec 2011 05:00:00 +0100 5491447 Mining the LIPG Allelic Spectrum Reveals the Contribution of Rare and Common Regulatory Variants to HDL Cholesterol http://www.medworm.com/index.php?rid=5491446&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FvxR7TAsUu5A%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002393 by Sumeet A. Khetarpal, Andrew C. Edmondson, Avanthi Raghavan, Hemanth Neeli, Weijun Jin, Karen O. Badellino, Serkalem Demissie, Alisa K. Manning, Stephanie L. DerOhannessian, Megan L. Wolfe, L. Adrienne Cupples, Mingyao Li, Sekar Kathiresan, Daniel J. Rader Genome-wide association studies (GWAS) have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact. Whereas rare variant efforts have primarily focused on nonsynonymous coding variants, we hypothesized that noncoding variants in these... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5491446 Thu, 08 Dec 2011 05:00:00 +0100 5491446 Mechanisms Establishing TLR4-Responsive Activation States of Inflammatory Response Genes http://www.medworm.com/index.php?rid=5491445&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fnia1aNJtTJQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002401 by Laure Escoubet-Lozach, Christopher Benner, Minna U. Kaikkonen, Jean Lozach, Sven Heinz, Nathan J. Spann, Andrea Crotti, Josh Stender, Serena Ghisletti, Donna Reichart, Christine S. Cheng, Rosa Luna, Colleen Ludka, Roman Sasik, Ivan Garcia-Bassets, Alexander Hoffmann, Shankar Subramaniam, Gary Hardiman, Michael G. Rosenfeld, Christopher K. Glass Precise control of the innate immune response is required for resistance to microbial infections and maintenance of normal tissue homeostasis. Because this response involves coordinate regulation of hundreds of genes, it provides a powerful biological system to elucidate the molecular strategies that underlie signal- and time-dependent transitions of gene expression. Comprehensive genome-wide analysis of the epigenetic and transcription stat... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5491445 Thu, 08 Dec 2011 05:00:00 +0100 5491445 Genomic Distribution and Inter-Sample Variation of Non-CpG Methylation across Human Cell Types http://www.medworm.com/index.php?rid=5491444&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FAwf45qphq_8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002389 by Michael J. Ziller, Fabian Müller, Jing Liao, Yingying Zhang, Hongcang Gu, Christoph Bock, Patrick Boyle, Charles B. Epstein, Bradley E. Bernstein, Thomas Lengauer, Andreas Gnirke, Alexander Meissner DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability, and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpT, and CpC (non-CpG) dinucleotides. Here we report a comprehensive analysis of non-CpG methylation in 76 genome-scale DNA methylation m... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5491444 Thu, 08 Dec 2011 05:00:00 +0100 5491444 The Major Roles of DNA Polymerases Epsilon and Delta at the Eukaryotic Replication Fork Are Evolutionarily Conserved http://www.medworm.com/index.php?rid=5463644&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F9s5saeuG9LA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002407 by Izumi Miyabe, Thomas A. Kunkel, Antony M. Carr Coordinated replication of eukaryotic genomes is intrinsically asymmetric, with continuous leading strand synthesis preceding discontinuous lagging strand synthesis. Here we provide two types of evidence indicating that, in fission yeast, these two biosynthetic tasks are performed by two different replicases. First, in Schizosaccharomyces pombe strains encoding a polδ-L591M mutator allele, base substitutions in reporter genes placed in opposite orientations relative to a well-characterized replication origin are strand-specific and distributed in patterns implying that Polδ is primarily involved in lagging strand replication. Second, in strains encoding a polε-M630F allele and lacking the ability to repair rNMPs in DNA due to a defe... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463644 Thu, 01 Dec 2011 05:00:00 +0100 5463644 The RNA–Methyltransferase Misu (NSun2) Poises Epidermal Stem Cells to Differentiate http://www.medworm.com/index.php?rid=5463643&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F-gp-Srthqb4%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002403 by Sandra Blanco, Agata Kurowski, Jennifer Nichols, Fiona M. Watt, Salvador Aznar Benitah, Michaela Frye Homeostasis of most adult tissues is maintained by balancing stem cell self-renewal and differentiation, but whether post-transcriptional mechanisms can regulate this process is unknown. Here, we identify that an RNA methyltransferase (Misu/Nsun2) is required to balance stem cell self-renewal and differentiation in skin. In the epidermis, this methyltransferase is found in a defined sub-population of hair follicle stem cells poised to undergo lineage commitment, and its depletion results in enhanced quiescence and aberrant stem cell differentiation. Our results reveal that post-transcriptional RNA methylation can play a previously unappreciated role in controlling stem cell fate. (... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463643 Thu, 01 Dec 2011 05:00:00 +0100 5463643 Genome-Wide Meta-Analysis of Five Asian Cohorts Identifies PDGFRA as a Susceptibility Locus for Corneal Astigmatism http://www.medworm.com/index.php?rid=5463642&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FuUiuWQbq3Gc%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002402 by Qiao Fan, Xin Zhou, Chiea-Chuen Khor, Ching-Yu Cheng, Liang-Kee Goh, Xueling Sim, Wan-Ting Tay, Yi-Ju Li, Rick Twee-Hee Ong, Chen Suo, Belinda Cornes, Mohammad Kamran Ikram, Kee-Seng Chia, Mark Seielstad, Jianjun Liu, Eranga Vithana, Terri L. Young, E.-Shyong Tai, Tien-Yin Wong, Tin Aung, Yik-Ying Teo, Seang-Mei Saw Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmat... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463642 Thu, 01 Dec 2011 05:00:00 +0100 5463642 Charcot-Marie-Tooth–Linked Mutant GARS Is Toxic to Peripheral Neurons Independent of Wild-Type GARS Levels http://www.medworm.com/index.php?rid=5463641&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FOrofLOeSE0c%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002399 by William W. Motley, Kevin L. Seburn, Mir Hussain Nawaz, Kathy E. Miers, Jun Cheng, Anthony Antonellis, Eric D. Green, Kevin Talbot, Xiang-Lei Yang, Kenneth H. Fischbeck, Robert W. Burgess Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). In addition to GARS, mutations in three other tRNA synthetase genes cause similar neuropathies, although the underlying mechanisms are not fully understood. To address this, we generated transgenic mice that ubiquitously over-express wild-type GARS and crossed them to two dominant mouse models of CMT2D to distinguish loss-of-function and gain-of-function mechanisms. Over-expression of wild-type GARS does not improve the neuropathy phenot... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463641 Thu, 01 Dec 2011 05:00:00 +0100 5463641 Widespread Cotranslational Formation of Protein Complexes http://www.medworm.com/index.php?rid=5463640&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FAgPfSkebyUU%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002398 by Caia D. S. Duncan, Juan Mata Most cellular processes are conducted by multi-protein complexes. However, little is known about how these complexes are assembled. In particular, it is not known if they are formed while one or more members of the complexes are being translated (cotranslational assembly). We took a genomic approach to address this question, by systematically identifying mRNAs associated with specific proteins. In a sample of 31 proteins from Schizosaccharomyces pombe that did not contain RNA–binding domains, we found that ∼38% copurify with mRNAs that encode interacting proteins. For example, the cyclin-dependent kinase Cdc2p associates with the rum1 and cdc18 mRNAs, which encode, respectively, an inhibitor of Cdc2p kinase activity and an essential regulator of DNA... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463640 Thu, 01 Dec 2011 05:00:00 +0100 5463640 Targeted Proteolysis of Plectin Isoform 1a Accounts for Hemidesmosome Dysfunction in Mice Mimicking the Dominant Skin Blistering Disease EBS-Ogna http://www.medworm.com/index.php?rid=5463639&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FoLU-Bk_EJPw%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002396 by Gernot Walko, Nevena Vukasinovic, Karin Gross, Irmgard Fischer, Sabrina Sibitz, Peter Fuchs, Siegfried Reipert, Ute Jungwirth, Walter Berger, Ulrich Salzer, Oliviero Carugo, Maria J. Castañón, Gerhard Wiche Autosomal recessive mutations in the cytolinker protein plectin account for the multisystem disorders epidermolysis bullosa simplex (EBS) associated with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and congenital myasthenia (EBS-CMS). In contrast, a dominant missense mutation leads to the disease EBS-Ogna, manifesting exclusively as skin fragility. We have exploited this trait to study the molecular basis of hemidesmosome failure in EBS-Ogna and to reveal the contribution of plectin to hemidesmosome homeostasis. We generated EBS-Ogna knock-in mice mimicking the huma... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463639 Thu, 01 Dec 2011 05:00:00 +0100 5463639 A Population Genetics-Phylogenetics Approach to Inferring Natural Selection in Coding Sequences http://www.medworm.com/index.php?rid=5463638&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F-ugDReLyNBA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002395 by Daniel J. Wilson, Ryan D. Hernandez, Peter Andolfatto, Molly Przeworski Through an analysis of polymorphism within and divergence between species, we can hope to learn about the distribution of selective effects of mutations in the genome, changes in the fitness landscape that occur over time, and the location of sites involved in key adaptations that distinguish modern-day species. We introduce a novel method for the analysis of variation in selection pressures within and between species, spatially along the genome and temporally between lineages. We model codon evolution explicitly using a joint population genetics-phylogenetics approach that we developed for the construction of multiallelic models with mutation, selection, and drift. Our approach has the advantage of performing ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463638 Thu, 01 Dec 2011 05:00:00 +0100 5463638 Identification of a Genomic Reservoir for New TRIM Genes in Primate Genomes http://www.medworm.com/index.php?rid=5463637&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FKZRWYWTnC5M%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002388 by Kyudong Han, Dianne I. Lou, Sara L. Sawyer Tripartite Motif (TRIM) ubiquitin ligases act in the innate immune response against viruses. One of the best characterized members of this family, TRIM5α, serves as a potent retroviral restriction factor with activity against HIV. Here, we characterize what are likely to be the youngest TRIM genes in the human genome. For instance, we have identified 11 TRIM genes that are specific to humans and African apes (chimpanzees, bonobos, and gorillas) and another 7 that are human-specific. Many of these young genes have never been described, and their identification brings the total number of known human TRIM genes to approximately 100. These genes were acquired through segmental duplications, most of which originated from a single locus on chro... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463637 Thu, 01 Dec 2011 05:00:00 +0100 5463637 The Fission Yeast Stress-Responsive MAPK Pathway Promotes Meiosis via the Phosphorylation of Pol II CTD in Response to Environmental and Feedback Cues http://www.medworm.com/index.php?rid=5463636&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F3b18rllCmag%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002387 This study also demonstrates clearly that the stress-responsive MAP kinase pathway can modulates gene expression through phosphorylation of Pol II CTD. (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463636 Thu, 01 Dec 2011 05:00:00 +0100 5463636 Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO/TREX http://www.medworm.com/index.php?rid=5463635&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FRfpJSmlCQrc%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002386 by María S. Domínguez-Sánchez, Sonia Barroso, Belén Gómez-González, Rosa Luna, Andrés Aguilera THO/TREX connects transcription with genome integrity in yeast, but a role of mammalian THO in these processes is uncertain, which suggests a differential implication of mRNP biogenesis factors in genome integrity in yeast and humans. We show that human THO depletion impairs transcription elongation and mRNA export and increases instability associated with DNA breaks, leading to hyper-recombination and γH2AX and 53BP1 foci accumulation. This is accompanied by replication alteration as determined by DNA combing. Genome instability is R-loop–dependent, as deduced from the ability of the AID enzyme to increase DNA damage and of RNaseH to reduce it, or from the enhancement of R-loop–... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463635 Thu, 01 Dec 2011 05:00:00 +0100 5463635 Repetitive Elements May Comprise Over Two-Thirds of the Human Genome http://www.medworm.com/index.php?rid=5463634&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F7nHN9RNcLck%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002384 by A. P. Jason de Koning, Wanjun Gu, Todd A. Castoe, Mark A. Batzer, David D. Pollock Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo “clouds”). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463634 Thu, 01 Dec 2011 05:00:00 +0100 5463634 Hierarchical Generalized Linear Models for Multiple Groups of Rare and Common Variants: Jointly Estimating Group and Individual-Variant Effects http://www.medworm.com/index.php?rid=5463633&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F2VK0Lq5ibSo%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002382 by Nengjun Yi, Nianjun Liu, Degui Zhi, Jun Li Complex diseases and traits are likely influenced by many common and rare genetic variants and environmental factors. Detecting disease susceptibility variants is a challenging task, especially when their frequencies are low and/or their effects are small or moderate. We propose here a comprehensive hierarchical generalized linear model framework for simultaneously analyzing multiple groups of rare and common variants and relevant covariates. The proposed hierarchical generalized linear models introduce a group effect and a genetic score (i.e., a linear combination of main-effect predictors for genetic variants) for each group of variants, and jointly they estimate the group effects and the weights of the genetic scores. This framework inc... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463633 Thu, 01 Dec 2011 05:00:00 +0100 5463633 SREBP Coordinates Iron and Ergosterol Homeostasis to Mediate Triazole Drug and Hypoxia Responses in the Human Fungal Pathogen Aspergillus fumigatus http://www.medworm.com/index.php?rid=5463632&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F0i18OxEcAVw%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002374 by Michael Blatzer, Bridget M. Barker, Sven D. Willger, Nicola Beckmann, Sara J. Blosser, Elizabeth J. Cornish, Aurelien Mazurie, Nora Grahl, Hubertus Haas, Robert A. Cramer Sterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. Adding to the recognized importance of SREBPs in human health, SREBPs in the human fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus are required for fungal virulence and susceptibility to triazole antifungal drugs. To date, the exact mechanism(s) behind the role of SREBP in these observed phenotypes is not clear. Here, we report that A. fumigatus SREBP, SrbA, mediates regulation of iron acquisition in response to hypoxia and low ir... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463632 Thu, 01 Dec 2011 05:00:00 +0100 5463632 Integrating Genome-Wide Genetic Variations and Monocyte Expression Data Reveals Trans-Regulated Gene Modules in Humans http://www.medworm.com/index.php?rid=5463631&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FoD65xCjyrRA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002367 This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease. (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5463631 Thu, 01 Dec 2011 05:00:00 +0100 5463631 TRY-5 Is a Sperm-Activating Protease in Caenorhabditis elegans Seminal Fluid http://www.medworm.com/index.php?rid=5426951&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FAV9SAdTaizY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002375 by Joseph R. Smith, Gillian M. Stanfield Seminal fluid proteins have been shown to play important roles in male reproductive success, but the mechanisms for this regulation remain largely unknown. In Caenorhabditis elegans, sperm differentiate from immature spermatids into mature, motile spermatozoa during a process termed sperm activation. For C. elegans males, sperm activation occurs during insemination of the hermaphrodite and is thought to be mediated by seminal fluid, but the molecular nature of this activity has not been previously identified. Here we show that TRY-5 is a seminal fluid protease that is required in C. elegans for male-mediated sperm activation. We observed that TRY-5::GFP is expressed in the male somatic gonad and is transferred along with sperm to hermaphrodites... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426951 Thu, 17 Nov 2011 05:00:00 +0100 5426951 PBX1 Genomic Pioneer Function Drives ERα Signaling Underlying Progression in Breast Cancer http://www.medworm.com/index.php?rid=5426950&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FriS9iwmyHeY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002368 by Luca Magnani, Elizabeth B. Ballantyne, Xiaoyang Zhang, Mathieu Lupien Altered transcriptional programs are a hallmark of diseases, yet how these are established is still ill-defined. PBX1 is a TALE homeodomain protein involved in the development of different types of cancers. The estrogen receptor alpha (ERα) is central to the development of two-thirds of all breast cancers. Here we demonstrate that PBX1 acts as a pioneer factor and is essential for the ERα-mediated transcriptional response driving aggressive tumors in breast cancer. Indeed, PBX1 expression correlates with ERα in primary breast tumors, and breast cancer cells depleted of PBX1 no longer proliferate following estrogen stimulation. Profiling PBX1 recruitment and chromatin accessibility across the genome of breast c... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426950 Thu, 17 Nov 2011 05:00:00 +0100 5426950 Role of Pirh2 in Mediating the Regulation of p53 and c-Myc http://www.medworm.com/index.php?rid=5426949&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F8xNfSuwqCaM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002360 by Anne Hakem, Miyuki Bohgaki, Bénédicte Lemmers, Elisabeth Tai, Leonardo Salmena, Elzbieta Matysiak-Zablocki, Yong-Sam Jung, Jana Karaskova, Lilia Kaustov, Shili Duan, Jason Madore, Paul Boutros, Yi Sheng, Marta Chesi, P. Leif Bergsagel, Bayardo Perez-Ordonez, Anne-Marie Mes-Masson, Linda Penn, Jeremy Squire, Xinbin Chen, Igor Jurisica, Cheryl Arrowsmith, Otto Sanchez, Samuel Benchimol, Razqallah Hakem Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel in... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426949 Thu, 17 Nov 2011 05:00:00 +0100 5426949 The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis http://www.medworm.com/index.php?rid=5426948&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FNVmGWAjXTsk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002365 by Jennifer M. Friederichs, Suman Ghosh, Christine J. Smoyer, Scott McCroskey, Brandon D. Miller, Kyle J. Weaver, Kym M. Delventhal, Jay Unruh, Brian D. Slaughter, Sue L. Jaspersen The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426948 Thu, 17 Nov 2011 05:00:00 +0100 5426948 Evidence-Based Annotation of Gene Function in Shewanella oneidensis MR-1 Using Genome-Wide Fitness Profiling across 121 Conditions http://www.medworm.com/index.php?rid=5426947&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FiwXMD_0PDYg%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002385 by Adam Deutschbauer, Morgan N. Price, Kelly M. Wetmore, Wenjun Shao, Jason K. Baumohl, Zhuchen Xu, Michelle Nguyen, Raquel Tamse, Ronald W. Davis, Adam P. Arkin Most genes in bacteria are experimentally uncharacterized and cannot be annotated with a specific function. Given the great diversity of bacteria and the ease of genome sequencing, high-throughput approaches to identify gene function experimentally are needed. Here, we use pools of tagged transposon mutants in the metal-reducing bacterium Shewanella oneidensis MR-1 to probe the mutant fitness of 3,355 genes in 121 diverse conditions including different growth substrates, alternative electron acceptors, stresses, and motility. We find that 2,350 genes have a pattern of fitness that is significantly different from random and 1,... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426947 Thu, 17 Nov 2011 05:00:00 +0100 5426947 Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways http://www.medworm.com/index.php?rid=5426946&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fcy8_qjk9yV8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002377 by Mohan Babu, J. Javier Díaz-Mejía, James Vlasblom, Alla Gagarinova, Sadhna Phanse, Chris Graham, Fouad Yousif, Huiming Ding, Xuejian Xiong, Anaies Nazarians-Armavil, Md Alamgir, Mehrab Ali, Oxana Pogoutse, Asaf Pe'er, Roland Arnold, Magali Michaut, John Parkinson, Ashkan Golshani, Chris Whitfield, Shoshana J. Wodak, Gabriel Moreno-Hagelsieb, Jack F. Greenblatt, Andrew Emili As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426946 Thu, 17 Nov 2011 05:00:00 +0100 5426946 Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity http://www.medworm.com/index.php?rid=5426945&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FXL5UdgSFzRQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002391 by Claire E. Richardson, Stephanie Kinkel, Dennis H. Kim Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiological conditions, in the absence of chemical agents administered to induce ER stress, is not well understood. Here, we show that in Caenorhabditis elegans XBP-1 deficiency results in constitutive ER stress, reflected by increased basal levels of IRE-1 and PEK-1 activity under physiological conditions. We define a dynamic, temperature-dependent requirement for XBP-1 and PEK-1 activities that increases with immune acti... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426945 Thu, 17 Nov 2011 05:00:00 +0100 5426945 Effect of Host Species on the Distribution of Mutational Fitness Effects for an RNA Virus http://www.medworm.com/index.php?rid=5426944&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FTD25_vClcSU%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002378 by Jasna Lalić, José M. Cuevas, Santiago F. Elena Knowledge about the distribution of mutational fitness effects (DMFE) is essential for many evolutionary models. In recent years, the properties of the DMFE have been carefully described for some microorganisms. In most cases, however, this information has been obtained only for a single environment, and very few studies have explored the effect that environmental variation may have on the DMFE. Environmental effects are particularly relevant for the evolution of multi-host parasites and thus for the emergence of new pathogens. Here we characterize the DMFE for a collection of twenty single-nucleotide substitution mutants of Tobacco etch potyvirus (TEV) across a set of eight host environments. Five of these host species were naturall... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426944 Thu, 17 Nov 2011 05:00:00 +0100 5426944 The NF1 Gene Contains Hotspots for L1 Endonuclease-Dependent De Novo Insertion http://www.medworm.com/index.php?rid=5426943&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FXozY-QlqXac%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002371 by Katharina Wimmer, Tom Callens, Annekatrin Wernstedt, Ludwine Messiaen Long interspersed (L1) and Alu elements are actively amplified in the human genome through retrotransposition of their RNA intermediates by the ∼100 still retrotranspositionally fully competent L1 elements. Retrotransposition can cause inherited disease if such an element is inserted near or within a functional gene. Using direct cDNA sequencing as the primary assay for comprehensive NF1 mutation analysis, we uncovered in 18 unrelated index patients splicing alterations not readily explained at the genomic level by an underlying point-mutation or deletion. Improved PCR protocols avoiding allelic drop-out of the mutant alleles uncovered insertions of fourteen Alu elements, three L1 elements, and one poly(T) stre... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426943 Thu, 17 Nov 2011 05:00:00 +0100 5426943 For Male Caenorhabditis elegans, Sperm Activation Is a “Just-in-Time” Event http://www.medworm.com/index.php?rid=5426942&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FN4cQILyPb_k%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002392 by Diane C. Shakes (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426942 Thu, 17 Nov 2011 05:00:00 +0100 5426942 Distinct Genetic Architectures for Male and Female Inflorescence Traits of Maize http://www.medworm.com/index.php?rid=5426941&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FUle0xv1_Msk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002383 by Patrick J. Brown, Narasimham Upadyayula, Gregory S. Mahone, Feng Tian, Peter J. Bradbury, Sean Myles, James B. Holland, Sherry Flint-Garcia, Michael D. McMullen, Edward S. Buckler, Torbert R. Rocheford We compared the genetic architecture of thirteen maize morphological traits in a large population of recombinant inbred lines. Four traits from the male inflorescence (tassel) and three traits from the female inflorescence (ear) were measured and studied using linkage and genome-wide association analyses and compared to three flowering and three leaf traits previously studied in the same population. Inflorescence loci have larger effects than flowering and leaf loci, and ear effects are larger than tassel effects. Ear trait models also have lower predictive ability than tassel, flowe... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426941 Thu, 17 Nov 2011 05:00:00 +0100 5426941 Heritable Epigenetic Variation among Maize Inbreds http://www.medworm.com/index.php?rid=5426940&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FKIHZDcaYQCA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002372 This study provides evidence for naturally occurring epigenetic variation in maize, including examples of pure epigenetic variation that is not conditioned by genetic differences. The epigenetic differences are variable within maize populations and exhibit relatively stable trans-generational inheritance. The detected examples of epigenetic variation, including some without tightly linked genetic variation, may contribute to complex trait variation. (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5426940 Thu, 17 Nov 2011 05:00:00 +0100 5426940 De Novo Origins of Human Genes http://www.medworm.com/index.php?rid=5394437&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FlOIG-m1MhaY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002381 by Daniele Guerzoni, Aoife McLysaght (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394437 Thu, 10 Nov 2011 05:00:00 +0100 5394437 De Novo Origin of Human Protein-Coding Genes http://www.medworm.com/index.php?rid=5394436&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F3oRB0z5CUkw%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002379 by Dong-Dong Wu, David M. Irwin, Ya-Ping Zhang The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA–seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the imp... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394436 Thu, 10 Nov 2011 05:00:00 +0100 5394436 Histone H3K56 Acetylation, CAF1, and Rtt106 Coordinate Nucleosome Assembly and Stability of Advancing Replication Forks http://www.medworm.com/index.php?rid=5394435&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FUUB_wzjKUDk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002376 by Marta Clemente-Ruiz, Román González-Prieto, Félix Prado Chromatin assembly mutants accumulate recombinogenic DNA damage and are sensitive to genotoxic agents. Here we have analyzed why impairment of the H3K56 acetylation-dependent CAF1 and Rtt106 chromatin assembly pathways, which have redundant roles in H3/H4 deposition during DNA replication, leads to genetic instability. We show that the absence of H3K56 acetylation or the simultaneous knock out of CAF1 and Rtt106 increases homologous recombination by affecting the integrity of advancing replication forks, while they have a minor effect on stalled replication fork stability in response to the replication inhibitor hydroxyurea. This defect in replication fork integrity is not due to defective checkpoints. In contrast, H3K56 ac... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394435 Thu, 10 Nov 2011 05:00:00 +0100 5394435 FOXO Regulates Organ-Specific Phenotypic Plasticity In Drosophila http://www.medworm.com/index.php?rid=5394434&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FhICQrPlDTEo%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002373 by Hui Yuan Tang, Martha S. B. Smith-Caldas, Michael V. Driscoll, Samy Salhadar, Alexander W. Shingleton Phenotypic plasticity, the ability for a single genotype to generate different phenotypes in response to environmental conditions, is biologically ubiquitous, and yet almost nothing is known of the developmental mechanisms that regulate the extent of a plastic response. In particular, it is unclear why some traits or individuals are highly sensitive to an environmental variable while other traits or individuals are less so. Here we elucidate the developmental mechanisms that regulate the expression of a particularly important form of phenotypic plasticity: the effect of developmental nutrition on organ size. In all animals, developmental nutrition is signaled to growing organs via ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394434 Thu, 10 Nov 2011 05:00:00 +0100 5394434 The ERI-6/7 Helicase Acts at the First Stage of an siRNA Amplification Pathway That Targets Recent Gene Duplications http://www.medworm.com/index.php?rid=5394433&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FSgCbGNY2_6w%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002369 by Sylvia E. J. Fischer, Taiowa A. Montgomery, Chi Zhang, Noah Fahlgren, Peter C. Breen, Alexia Hwang, Christopher M. Sullivan, James C. Carrington, Gary Ruvkun Endogenous small interfering RNAs (siRNAs) are a class of naturally occuring regulatory RNAs found in fungi, plants, and animals. Some endogenous siRNAs are required to silence transposons or function in chromosome segregation; however, the specific roles of most endogenous siRNAs are unclear. The helicase gene eri-6/7 was identified in the nematode Caenorhabditis elegans by the enhanced response to exogenous double-stranded RNAs (dsRNAs) of the null mutant. eri-6/7 encodes a helicase homologous to small RNA factors Armitage in Drosophila, SDE3 in Arabidopsis, and Mov10 in humans. Here we show that eri-6/7 mutations cause the ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394433 Thu, 10 Nov 2011 05:00:00 +0100 5394433 Arabidopsis Homologs of Retinoblastoma-Associated Protein 46/48 Associate with a Histone Deacetylase to Act Redundantly in Chromatin Silencing http://www.medworm.com/index.php?rid=5394432&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FnW9ma0EGBRs%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002366 by Xiaofeng Gu, Danhua Jiang, Wannian Yang, Yannick Jacob, Scott D. Michaels, Yuehui He RNA molecules such as small-interfering RNAs (siRNAs) and antisense RNAs (asRNAs) trigger chromatin silencing of target loci. In the model plant Arabidopsis, RNA–triggered chromatin silencing involves repressive histone modifications such as histone deacetylation, histone H3 lysine-9 methylation, and H3 lysine-27 monomethylation. Here, we report that two Arabidopsis homologs of the human histone-binding proteins Retinoblastoma-Associated Protein 46/48 (RbAp46/48), known as MSI4 (or FVE) and MSI5, function in partial redundancy in chromatin silencing of various loci targeted by siRNAs or asRNAs. We show that MSI5 acts in partial redundancy with FVE to silence FLOWERING LOCUS C (FLC), which is a cr... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394432 Thu, 10 Nov 2011 05:00:00 +0100 5394432 Consequences of Eukaryotic Enhancer Architecture for Gene Expression Dynamics, Development, and Fitness http://www.medworm.com/index.php?rid=5394431&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FJnGe_VNA6Os%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002364 by Michael Z. Ludwig, Manu, Ralf Kittler, Kevin P. White, Martin Kreitman The regulatory logic of time- and tissue-specific gene expression has mostly been dissected in the context of the smallest DNA fragments that, when isolated, recapitulate native expression in reporter assays. It is not known if the genomic sequences surrounding such fragments, often evolutionarily conserved, have any biological function or not. Using an enhancer of the even-skipped gene of Drosophila as a model, we investigate the functional significance of the genomic sequences surrounding empirically identified enhancers. A 480 bp long “minimal stripe element” is able to drive even-skipped expression in the second of seven stripes but is embedded in a larger region of 800 bp containing evolutionarily conse... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394431 Thu, 10 Nov 2011 05:00:00 +0100 5394431 Capture of MicroRNA–Bound mRNAs Identifies the Tumor Suppressor miR-34a as a Regulator of Growth Factor Signaling http://www.medworm.com/index.php?rid=5394430&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F7MexezIHU54%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002363 by Ashish Lal, Marshall P. Thomas, Gabriel Altschuler, Francisco Navarro, Elizabeth O'Day, Xiao Ling Li, Carla Concepcion, Yoon-Chi Han, Jerome Thiery, Danielle K. Rajani, Aaron Deutsch, Oliver Hofmann, Andrea Ventura, Winston Hide, Judy Lieberman A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ∼90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394430 Thu, 10 Nov 2011 05:00:00 +0100 5394430 Caenorhabditis elegans Cyclin D/CDK4 and Cyclin E/CDK2 Induce Distinct Cell Cycle Re-Entry Programs in Differentiated Muscle Cells http://www.medworm.com/index.php?rid=5394429&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FnzpRVBZtpIk%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002362 by Jerome Korzelius, Inge The, Suzan Ruijtenberg, Martine B. W. Prinsen, Vincent Portegijs, Teije C. Middelkoop, Marian J. Groot Koerkamp, Frank C. P. Holstege, Mike Boxem, Sander van den Heuvel Cell proliferation and differentiation are regulated in a highly coordinated and inverse manner during development and tissue homeostasis. Terminal differentiation usually coincides with cell cycle exit and is thought to engage stable transcriptional repression of cell cycle genes. Here, we examine the robustness of the post-mitotic state, using Caenorhabditis elegans muscle cells as a model. We found that expression of a G1 Cyclin and CDK initiates cell cycle re-entry in muscle cells without interfering with the differentiated state. Cyclin D/CDK4 (CYD-1/CDK-4) expression was sufficient to in... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394429 Thu, 10 Nov 2011 05:00:00 +0100 5394429 Serratia symbiotica from the Aphid Cinara cedri: A Missing Link from Facultative to Obligate Insect Endosymbiont http://www.medworm.com/index.php?rid=5394428&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FDGxtQ5303tA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002357 by Araceli Lamelas, María José Gosalbes, Alejandro Manzano-Marín, Juli Peretó, Andrés Moya, Amparo Latorre The genome sequencing of Buchnera aphidicola BCc from the aphid Cinara cedri, which is the smallest known Buchnera genome, revealed that this bacterium had lost its symbiotic role, as it was not able to synthesize tryptophan and riboflavin. Moreover, the biosynthesis of tryptophan is shared with the endosymbiont Serratia symbiotica SCc, which coexists with B. aphidicola in this aphid. The whole-genome sequencing of S. symbiotica SCc reveals an endosymbiont in a stage of genome reduction that is closer to an obligate endosymbiont, such as B. aphidicola from Acyrthosiphon pisum, than to another S. symbiotica, which is a facultative endosymbiont in this aphid, and presents much... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394428 Thu, 10 Nov 2011 05:00:00 +0100 5394428 Multiple Means to the Same End: The Genetic Basis of Acquired Stress Resistance in Yeast http://www.medworm.com/index.php?rid=5394427&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FmgX6-waYzb8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002353 by David B. Berry, Qiaoning Guan, James Hose, Suraiya Haroon, Marinella Gebbia, Lawrence E. Heisler, Corey Nislow, Guri Giaever, Audrey P. Gasch In nature, stressful environments often occur in combination or close succession, and thus the ability to prepare for impending stress likely provides a significant fitness advantage. Organisms exposed to a mild dose of stress can become tolerant to what would otherwise be a lethal dose of subsequent stress; however, the mechanism of this acquired stress tolerance is poorly understood. To explore this, we exposed the yeast gene-deletion libraries, which interrogate all essential and non-essential genes, to successive stress treatments and identified genes necessary for acquiring subsequent stress resistance. Cells were exposed to one of three... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394427 Thu, 10 Nov 2011 05:00:00 +0100 5394427 Relative Burden of Large CNVs on a Range of Neurodevelopmental Phenotypes http://www.medworm.com/index.php?rid=5394426&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FZPu13gP9mGM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002334 by Santhosh Girirajan, Zoran Brkanac, Bradley P. Coe, Carl Baker, Laura Vives, Tiffany H. Vu, Neil Shafer, Raphael Bernier, Giovanni B. Ferrero, Margherita Silengo, Stephen T. Warren, Carlos S. Moreno, Marco Fichera, Corrado Romano, Wendy H. Raskind, Evan E. Eichler While numerous studies have implicated copy number variants (CNVs) in a range of neurological phenotypes, the impact relative to disease severity has been difficult to ascertain due to small sample sizes, lack of phenotypic details, and heterogeneity in platforms used for discovery. Using a customized microarray enriched for genomic hotspots, we assayed for large CNVs among 1,227 individuals with various neurological deficits including dyslexia (376), sporadic autism (350), and intellectual disability (ID) (501), as well a... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5394426 Thu, 10 Nov 2011 05:00:00 +0100 5394426 PcG Complexes Set the Stage for Epigenetic Inheritance of Gene Silencing in Early S Phase before Replication http://www.medworm.com/index.php?rid=5372091&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FOyoEHjZ-ICQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002370 by Chiara Lanzuolo, Federica Lo Sardo, Adamo Diamantini, Valerio Orlando Polycomb group (PcG) proteins are part of a conserved cell memory system that conveys epigenetic inheritance of silenced transcriptional states through cell division. Despite the considerable amount of information about PcG mechanisms controlling gene silencing, how PcG proteins maintain repressive chromatin during epigenome duplication is still unclear. Here we identified a specific time window, the early S phase, in which PcG proteins are recruited at BX-C PRE target sites in concomitance with H3K27me3 repressive mark deposition. Notably, these events precede and are uncoupled from PRE replication timing, which occurs in late S phase when most epigenetic signatures are reduced. These findings shed light on one ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372091 Thu, 03 Nov 2011 04:00:00 +0100 5372091 Short Day–Mediated Cessation of Growth Requires the Downregulation of AINTEGUMENTALIKE1 Transcription Factor in Hybrid Aspen http://www.medworm.com/index.php?rid=5372090&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fy6f5gLaeF5g%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002361 by Anna Karlberg, Laszlo Bako, Rishikesh P. Bhalerao Day length is a key environmental cue regulating the timing of major developmental transitions in plants. For example, in perennial plants such as the long-lived trees of the boreal forest, exposure to short days (SD) leads to the termination of meristem activity and bud set (referred to as growth cessation). The mechanism underlying SD–mediated induction of growth cessation is poorly understood. Here we show that the AIL1-AIL4 (AINTEGUMENTALIKE) transcription factors of the AP2 family are the downstream targets of the SD signal in the regulation of growth cessation response in hybrid aspen trees. AIL1 is expressed in the shoot apical meristem and leaf primordia, and exposure to SD signal downregulates AIL1 expression. Downregulat... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372090 Thu, 03 Nov 2011 04:00:00 +0100 5372090 Activation of Bmp2-Smad1 Signal and Its Regulation by Coordinated Alteration of H3K27 Trimethylation in Ras-Induced Senescence http://www.medworm.com/index.php?rid=5372089&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FuxxD2gbiOag%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002359 by Atsushi Kaneda, Takanori Fujita, Motonobu Anai, Shogo Yamamoto, Genta Nagae, Masato Morikawa, Shingo Tsuji, Masanobu Oshima, Kohei Miyazono, Hiroyuki Aburatani Cellular senescence involves epigenetic alteration, e.g. loss of H3K27me3 in Ink4a-Arf locus. Using mouse embryonic fibroblast (MEF), we here analyzed transcription and epigenetic alteration during Ras-induced senescence on genome-wide scale by chromatin immunoprecipitation (ChIP)-sequencing and microarray. Bmp2 was the most activated secreted factor with H3K4me3 gain and H3K27me3 loss, whereas H3K4me3 loss and de novo formation of H3K27me3 occurred inversely in repression of nine genes, including two BMP-SMAD inhibitors Smad6 and Noggin. DNA methylation alteration unlikely occurred. Ras-activated cells senesced with nuclear... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372089 Thu, 03 Nov 2011 04:00:00 +0100 5372089 A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened http://www.medworm.com/index.php?rid=5372088&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fk6Sph9-k0wc%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002358 by Seongjin Seo, Qihong Zhang, Kevin Bugge, David K. Breslow, Charles C. Searby, Maxence V. Nachury, Val C. Sheffield Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372088 Thu, 03 Nov 2011 04:00:00 +0100 5372088 SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression http://www.medworm.com/index.php?rid=5372087&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2F7Q4iP-txrJ8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002356 by Victor Y. L. Leung, Bo Gao, Keith K. H. Leung, Ian G. Melhado, Sarah L. Wynn, Tiffany Y. K. Au, Nelson W. F. Dung, James Y. B. Lau, Angel C. Y. Mak, Danny Chan, Kathryn S. E. Cheah Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In im... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372087 Thu, 03 Nov 2011 04:00:00 +0100 5372087 Signatures of Environmental Genetic Adaptation Pinpoint Pathogens as the Main Selective Pressure through Human Evolution http://www.medworm.com/index.php?rid=5372086&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FMWMeiWztfMA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002355 by Matteo Fumagalli, Manuela Sironi, Uberto Pozzoli, Anna Ferrer-Admettla, Linda Pattini, Rasmus Nielsen Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribut... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372086 Thu, 03 Nov 2011 04:00:00 +0100 5372086 Genome-Wide Crossover Distribution in Arabidopsis thaliana Meiosis Reveals Sex-Specific Patterns along Chromosomes http://www.medworm.com/index.php?rid=5372085&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FRpYhjG5tNT8%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002354 by Laurène Giraut, Matthieu Falque, Jan Drouaud, Lucie Pereira, Olivier C. Martin, Christine Mézard In most species, crossovers (COs) are essential for the accurate segregation of homologous chromosomes at the first meiotic division. Their number and location are tightly regulated. Here, we report a detailed, genome-wide characterization of the rate and localization of COs in Arabidopsis thaliana, in male and female meiosis. We observed dramatic differences between male and female meiosis which included: (i) genetic map length; 575 cM versus 332 cM respectively; (ii) CO distribution patterns: male CO rates were very high at both ends of each chromosome, whereas female CO rates were very low; (iii) correlations between CO rates and various chromosome features: female CO rates correla... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372085 Thu, 03 Nov 2011 04:00:00 +0100 5372085 Recessive Antimorphic Alleles Overcome Functionally Redundant Loci to Reveal TSO1 Function in Arabidopsis Flowers and Meristems http://www.medworm.com/index.php?rid=5372084&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FKRDXoW6eP6c%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002352 This study shows that recessive alleles can also be antimorphic and can produce a phenotype more severe than null by interfering with the function of related loci. This finding adds a new paradigm to classical genetic concepts, with important implications for future genetic studies both in basic research as well as in agriculture and medicine. (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372084 Thu, 03 Nov 2011 04:00:00 +0100 5372084 Pch2 Acts through Xrs2 and Tel1/ATM to Modulate Interhomolog Bias and Checkpoint Function during Meiosis http://www.medworm.com/index.php?rid=5372083&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FLwBT28FKxdM%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002351 by Hsuan-Chung Ho, Sean M. Burgess Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs) to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA+-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in th... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372083 Thu, 03 Nov 2011 04:00:00 +0100 5372083 Attenuation of the Sensing Capabilities of PhoQ in Transition to Obligate Insect–Bacterial Association http://www.medworm.com/index.php?rid=5372082&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FqHMP5o-B74c%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002349 by Mauricio Henriques Pontes, Kari Lyn Smith, Linda De Vooght, Jan Van Den Abbeele, Colin Dale Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a regulator of key virulence determinants. In the current study, we show that the inactivation of the response regulator, phoP, renders S. glossinidius sensitive to insect derived cationic antimicrobial peptides (AMPs). The resulting mutant strain displays reduced expression of genes involved in the structural modification of lipid A that facilitates resistance to AMPs. In addition... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372082 Thu, 03 Nov 2011 04:00:00 +0100 5372082 Foxn1 Regulates Lineage Progression in Cortical and Medullary Thymic Epithelial Cells But Is Dispensable for Medullary Sublineage Divergence http://www.medworm.com/index.php?rid=5372081&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FcYvkcIMaM34%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002348 by Craig S. Nowell, Nicholas Bredenkamp, Stéphanie Tetélin, Xin Jin, Christin Tischner, Harsh Vaidya, Julie M. Sheridan, Frances Hogg Stenhouse, Raphaela Heussen, Andrew J. H. Smith, C. Clare Blackburn The forkhead transcription factor Foxn1 is indispensable for thymus development, but the mechanisms by which it mediates thymic epithelial cell (TEC) development are poorly understood. To examine the cellular and molecular basis of Foxn1 function, we generated a novel and revertible hypomorphic allele of Foxn1. By varying levels of its expression, we identified a number of features of the Foxn1 system. Here we show that Foxn1 is a powerful regulator of TEC differentiation that is required at multiple intermediate stages of TE lineage development in the fetal and adult thymus. We find ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372081 Thu, 03 Nov 2011 04:00:00 +0100 5372081 Over-Expression of DSCAM and COL6A2 Cooperatively Generates Congenital Heart Defects http://www.medworm.com/index.php?rid=5372080&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FGv3RFHIrkrg%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002344 by Tamar R. Grossman, Amir Gamliel, Robert J. Wessells, Ouarda Taghli-Lamallem, Kristen Jepsen, Karen Ocorr, Julie R. Korenberg, Kirk L. Peterson, Michael G. Rosenfeld, Rolf Bodmer, Ethan Bier A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS), which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD), and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first us... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372080 Thu, 03 Nov 2011 04:00:00 +0100 5372080 Drosophila Duplication Hotspots Are Associated with Late-Replicating Regions of the Genome http://www.medworm.com/index.php?rid=5372079&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fv2bDSfmKBTc%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002340 In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372079 Thu, 03 Nov 2011 04:00:00 +0100 5372079 Small RNAs Prevent Transcription-Coupled Loss of Histone H3 Lysine 9 Methylation in Arabidopsis thaliana http://www.medworm.com/index.php?rid=5372097&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FTqZafrdSees%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002350 by Raymond A. Enke, Zhicheng Dong, Judith Bender In eukaryotes, histone H3 lysine 9 methylation (H3K9me) mediates silencing of invasive sequences to prevent deleterious consequences including the expression of aberrant gene products and mobilization of transposons. In Arabidopsis thaliana, H3K9me maintained by SUVH histone methyltransferases (MTases) is associated with cytosine methylation (5meC) maintained by the CMT3 cytosine MTase. The SUVHs contain a 5meC binding domain and CMT3 contains an H3K9me binding domain, suggesting that the SUVH/CMT3 pathway involves an amplification loop between H3K9me and 5meC. However, at loci subject to read-through transcription, the stability of the H3K9me/5meC loop requires a mechanism to counteract transcription-coupled loss of H3K9me. Here we use... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372097 Thu, 27 Oct 2011 04:00:00 +0100 5372097 A Conserved Developmental Patterning Network Produces Quantitatively Different Output in Multiple Species of Drosophila http://www.medworm.com/index.php?rid=5372096&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FpaymjYgZdLA%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002346 We present an approach to compare cellular gene expression patterns between species, while accounting for varying embryo morphology, and apply it to our data and an equivalent dataset for Drosophila melanogaster. Our analysis reveals that all individual genes differ quantitatively in their spatio-temporal expression patterns between these species, primarily in terms of their relative position and dynamics. Despite many small quantitative differences, cellular gene expression profiles for the whole set of genes examined are largely similar. This suggests that cell types at this stage of development are conserved, though they can differ in their relative position by up to 3–4 cell widths and in their relative proportion between species by as much as 5-fold. Quantitative differences in the ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372096 Thu, 27 Oct 2011 04:00:00 +0100 5372096 Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis http://www.medworm.com/index.php?rid=5372095&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FutxfNyStquU%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002345 by Christopher A. Desjardins, Mia D. Champion, Jason W. Holder, Anna Muszewska, Jonathan Goldberg, Alexandre M. Bailão, Marcelo Macedo Brigido, Márcia Eliana da Silva Ferreira, Ana Maria Garcia, Marcin Grynberg, Sharvari Gujja, David I. Heiman, Matthew R. Henn, Chinnappa D. Kodira, Henry León-Narváez, Larissa V. G. Longo, Li-Jun Ma, Iran Malavazi, Alisson L. Matsuo, Flavia V. Morais, Maristela Pereira, Sabrina Rodríguez-Brito, Sharadha Sakthikumar, Silvia M. Salem-Izacc, Sean M. Sykes, Marcus Melo Teixeira, Milene C. Vallejo, Maria Emília Machado Telles Walter, Chandri Yandava, Sarah Young, Qiandong Zeng, Jeremy Zucker, Maria Sueli Felipe, Gustavo H. Goldman, Brian J. Haas, Juan G. McEwen, Gustavo Nino-Vega, Rosana Puccia, Gioconda San-Blas, Celia Maria de Almeida Soares, Bruce W. Bi... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372095 Thu, 27 Oct 2011 04:00:00 +0100 5372095 Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus http://www.medworm.com/index.php?rid=5372094&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FSx0LG2r4af4%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002341 by Deborah S. Cunninghame Graham, David L. Morris, Tushar R. Bhangale, Lindsey A. Criswell, Ann-Christine Syvänen, Lars Rönnblom, Timothy W. Behrens, Robert R. Graham, Timothy J. Vyse Systemic lupus erythematosus (SLE) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. Currently, ∼8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR>1.3). In order to identify additional genes contributing to SLE susceptibility, we conducted a replication study in a UK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association an... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372094 Thu, 27 Oct 2011 04:00:00 +0100 5372094 Role of Exonic Variation in Chemokine Receptor Genes on AIDS: CCRL2 F167Y Association with Pneumocystis Pneumonia http://www.medworm.com/index.php?rid=5372093&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FlWXSePJW7Rs%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002328 by Ping An, Rongling Li, Ji Ming Wang, Teizo Yoshimura, Munehisa Takahashi, Ram Samudralal, Stephen J. O'Brien, John Phair, James J. Goedert, Gregory D. Kirk, Jennifer L. Troyer, Efe Sezgin, Susan P. Buchbinder, Sharyne Donfield, George W. Nelson, Cheryl A. Winkler Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs ... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372093 Thu, 27 Oct 2011 04:00:00 +0100 5372093 Insights into Hox Protein Function from a Large Scale Combinatorial Analysis of Protein Domains http://www.medworm.com/index.php?rid=5372092&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FJZsrhj6xTHY%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002302 by Samir Merabet, Isma Litim-Mecheri, Daniel Karlsson, Richa Dixit, Mehdi Saadaoui, Bruno Monier, Christine Brun, Stefan Thor, K. Vijayraghavan, Laurent Perrin, Jacques Pradel, Yacine Graba Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and mu... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5372092 Thu, 27 Oct 2011 04:00:00 +0100 5372092 A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol http://www.medworm.com/index.php?rid=5342068&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FzWLjocHDDaE%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002333 by Ida Surakka, Aaron Isaacs, Lennart C. Karssen, Pirkka-Pekka P. Laurila, Rita P. S. Middelberg, Emmi Tikkanen, Janina S. Ried, Claudia Lamina, Massimo Mangino, Wilmar Igl, Jouke-Jan Hottenga, Vasiliki Lagou, Pim van der Harst, Irene Mateo Leach, Tõnu Esko, Zoltán Kutalik, Nicholas W. Wainwright, Maksim V. Struchalin, Antti-Pekka Sarin, Antti J. Kangas, Jorma S. Viikari, Markus Perola, Taina Rantanen, Ann-Kristin Petersen, Pasi Soininen, Åsa Johansson, Nicole Soranzo, Andrew C. Heath, Theodore Papamarkou, Inga Prokopenko, Anke Tönjes, Florian Kronenberg, Angela Döring, Fernando Rivadeneira, Grant W. Montgomery, John B. Whitfield, Mika Kähönen, Terho Lehtimäki, Nelson B. Freimer, Gonneke Willemsen, Eco J. C. de Geus, Aarno Palotie, Manj S. Sandhu, Dawn M. Waterworth, Andres Metspal... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5342068 Thu, 20 Oct 2011 04:00:00 +0100 5342068 Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population http://www.medworm.com/index.php?rid=5342067&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FStPjaj0vCEQ%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002343 by Andrew K. Turner, Mike Begon, Joseph A. Jackson, Janette E. Bradley, Steve Paterson Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis) to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5342067 Thu, 20 Oct 2011 04:00:00 +0100 5342067 Novel Function of Distal-less as a Gap Gene during Spider Segmentation http://www.medworm.com/index.php?rid=5342066&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FxdKqSupyrGw%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002342 by Matthias Pechmann, Sara Khadjeh, Natascha Turetzek, Alistair P. McGregor, Wim G. M. Damen, Nikola-Michael Prpic Despite many aspects of the regulation of segmentation being conserved among arthropods, the evolution of novel gene functions has played an important role in the evolution of developmental regulation and the emergence of new segmental structures. Moreover the study of such novel gene functions can be informative with respect to the patterns and direction of evolutionary changes in developmental programs. The homeobox gene Distal-less (Dll) is known for its conserved function in appendage development in metazoans. In arthropods, Dll is required for the specification of distal appendage structures. Here we describe a novel and unexpected role of Dll in the spider Achaearan... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5342066 Thu, 20 Oct 2011 04:00:00 +0100 5342066 Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration http://www.medworm.com/index.php?rid=5342065&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FIyw3zY284Iw%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002338 by Peter L. Oliver, Mattéa J. Finelli, Benjamin Edwards, Emmanuelle Bitoun, Darcy L. Butts, Esther B. E. Becker, Michael T. Cheeseman, Ben Davies, Kay E. Davies Oxidative stress is a common etiological feature of neurological disorders, although the pathways that govern defence against reactive oxygen species (ROS) in neurodegeneration remain unclear. We have identified the role of oxidation resistance 1 (Oxr1) as a vital protein that controls the sensitivity of neuronal cells to oxidative stress; mice lacking Oxr1 display cerebellar neurodegeneration, and neurons are less susceptible to exogenous stress when the gene is over-expressed. A conserved short isoform of Oxr1 is also sufficient to confer this neuroprotective property both in vitro and in vivo. In addition, biochemical assa... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5342065 Thu, 20 Oct 2011 04:00:00 +0100 5342065 An Adaptive Allelic Series Featuring Complex Gene Rearrangements http://www.medworm.com/index.php?rid=5342064&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2FltVjbCPFIQc%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002347 by Joshua M. Schmidt, Charles Robin (Source: PLoS Genetics) PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5342064 Thu, 20 Oct 2011 04:00:00 +0100 5342064 Successive Increases in the Resistance of Drosophila to Viral Infection through a Transposon Insertion Followed by a Duplication http://www.medworm.com/index.php?rid=5342063&cid=s_33038_50_f&fid=33038&url=http%3A%2F%2Ffeeds.plos.org%2F%7Er%2Fplosgenetics%2FNewArticles%2F%7E3%2Fm6So5rXsr8o%2Finfo%253Adoi%252F10.1371%252Fjournal.pgen.1002337 by Michael M. Magwire, Florian Bayer, Claire L. Webster, Chuan Cao, Francis M. Jiggins To understand the molecular basis of how hosts evolve resistance to their parasites, we have investigated the genes that cause variation in the susceptibility of Drosophila melanogaster to viral infection. Using a host-specific pathogen of D. melanogaster called the sigma virus (Rhabdoviridae), we mapped a major-effect polymorphism to a region containing two paralogous genes called CHKov1 and CHKov2. In a panel of inbred fly lines, we found that a transposable element insertion in the protein coding sequence of CHKov1 is associated with increased resistance to infection. Previous research has shown that this insertion results in a truncated messenger RNA that encodes a far shorter protein than the s... PLoS Genetics journals http://www.medworm.com/rss/comments.php?id=5342063 Thu, 20 Oct 2011 04:00:00 +0100 5342063