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1146 records returned

The Rts1 Regulatory Subunit of Protein Phosphatase 2A Is Required for Control of G1 Cyclin Transcription and Nutrient Modulation of Cell SizeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary A critical point in the cell cycle occurs in G1 phase, when cells must decide whether to enter a new round of cell division. At this time, cells assess nutrient availability to ensure that they have sufficient resources to complete cell growth and division. Vertebrate cells also assess growth factors that control cell growth and determine when and where cell division occurs in the context of a multi-cellular organism. A cell-size checkpoint acts during G1 to delay entry into the cell cycle if the cell is below a critical size. When the appropriate signals have been received, cells commit to entry into the c...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Karen Artiles et al. Source Type: journals

The Schizosaccharomyces pombe JmjC-Protein, Msc1, Prevents H2A.Z Localization in Centromeric and Subtelomeric Chromatin DomainsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Chromatin is based on a repetitive structural unit called the nucleosome. However, the regulatory properties of chromatin are mediated by the differences between nucleosomes, due to post-translational modifications or the inclusion of histone variants. These differences are maintained by inheritance through cis-acting epigenetic mechanisms. Here we describe a case where the local character of chromatin is not only determined by cis-acting mechanisms but also negatively regulated in trans. The case involves loading of the histone H2A variant, H2A.Z, into chromatin. We show that H2A.Z in the yeast Schizosacch...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Luke Buchanan et al. Source Type: journals

Ctp1 and the MRN-Complex Are Required for Endonucleolytic Rec12 Removal with Release of a Single Class of Oligonucleotides in Fission YeastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary A diploid zygote arises by fusion of two haploid gametes. The specific cell division leading to haploid gametes with haploid chromosome number, accompanied by recombination of genetic material, is called meiosis. It is essential for sexually reproducing eukaryotes. During meiotic prophase, shortly after DNA replication, programmed DNA double-strand breaks mark the initiation of recombination. In budding yeast, the protein responsible for DNA double-strand break formation, Spo11, creates a covalent DNA-Spo11 intermediate, which needs to be removed for subsequent recombination. Presumably, asymmetric endonucl...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Maja Rothenberg et al. Source Type: journals

Evolutionary Convergence and Nitrogen Metabolism in Blattabacterium strain Bge, Primary Endosymbiont of the Cockroach Blattella germanicaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Bacterial endosymbionts from insects are subjected to a process of genome reduction from the moment they interact with their host, especially when the symbiosis is strict (the partners live together permanently) and the endosymbiont is maternally inherited. The type of genes that are retained correlates with specific metabolic host requirements. Here, we report the genome sequence of Blattabacterium strain Bge, the primary endosymbiont of the German cockroach B. germanica. Cockroaches are omnivorous insects and Blattabacterium cooperates with their metabolism, not only with essential nutrient metabolism but...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Maria J. López-Sánchez et al. Source Type: journals

Lgl2 Executes Its Function as a Tumor Suppressor by Regulating ErbB Signaling in the Zebrafish EpidermisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary In metazoans, the body surface and linings of several organs are formed from membranous tissue called epithelia. The functions of epithelia include secretion, absorption, and protection. Epithelial cells exhibit polarized distribution of several proteins, which is essential for their function. In carcinomas, which are cancers of epithelial origin, this epithelial cell polarity is impaired. Intriguingly, defects in cell polarization can also lead to tumorigenesis in some animal model systems. It is thus important to understand how cell polarization and epithelial growth control are linked so as to treat the ...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Sven Reischauer et al. Source Type: journals

Gene Dosage, Expression, and Ontology Analysis Identifies Driver Genes in the Carcinogenesis and Chemoradioresistance of Cervical CancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Genetic gains and losses, i.e. changes in gene dosages, are common abnormalities of human cancers. Discovering these defects and understanding the biological meaning can lead to improved therapeutic opportunities. This paper reports a large scale screening of gene dosage alterations in cervical cancer and gives a broader exploration of the expression and function of genes with gains or losses. We have focused on the most frequent gene dosage alterations and the alterations associated with survival after chemoradiotherapy, since these defects are likely to be of major importance for developing disease. The m...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Malin Lando et al. Source Type: journals

A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem CellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Most complex traits likely result from a combination of genetic polymorphisms. The normal variation in gene expression is thought to be an important contributor. In order to examine a wide range of personalized tissue types from a given individual, we developed a robust method for detecting regulatory variants genome-wide in human induced pluripotent stem (iPS) cells. By having a platform capable of mapping regulatory variants despite large biological and experimental noise, and by being able to use in vitro differentiation to derive multiple human tissue types, our approach should enable the identification...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Je-Hyuk Lee et al. Source Type: journals

The Pivotal Roles of TIA Proteins in 5′ Splice-Site Selection of Alu Exons and Across EvolutionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Human genes are composed of functional regions, termed exons, separated by non-functional regions, termed introns. Intronic sequences may gradually accumulate mutations and subsequently become recognized by the splicing machinery as exons, a process termed exonization. Alu elements are prone to undergo exonization: more than 5% of alternatively spliced internal exons in the human genome originate from Alu elements. A typical Alu element is ~300 nucleotides long, consisting of two arms separated by a polypyrimdine tract (PPT). Interestingly, in most cases, exonization occurs almost exclusively within either ...
Source: PLoS Genetics - November 13, 2009 Category: Genetics & Stem Cells Authors: Nurit Gal-Mark et al. Source Type: journals

Localized Plasticity in the Streamlined Genomes of Vinyl Chloride Respiring DehalococcoidesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Dehalococcoides are free-living sediment and subsurface bacteria with remarkably small, streamlined genomes and an unusual degree of niche specialization. These strictly anaerobic bacteria gain metabolic energy exclusively through a novel type of respiration that results in reductive elimination of chlorides from organochlorines, many of which are priority pollutants. In this article, we compare the first complete genome sequences of Dehalococcoides strains that grow via respiration of vinyl chloride (VC), a human carcinogen and abundant groundwater pollutant. Our work provides novel insights into Dehalococ...
Source: PLoS Genetics - November 6, 2009 Category: Genetics & Stem Cells Authors: Paul J. McMurdie et al. Source Type: journals

E Unibus Plurum: Genomic Analysis of an Experimentally Evolved Polymorphism in Escherichia coliEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Authors Summary Experimental evolution of asexual species has shown that multiple genotypes can arise from a single ancestor and stably coexist (e unibus plurum). Although facilitated by environmental heterogeneity, this phenomenon also occurs in simple, homogeneous environments provisioned with a single limiting nutrient. We sought to discover genetic mechanisms that enabled an E. coli population founded by a single clone to become an interacting community composed of multiple clones. The founder of this population contained mutations that impair regulation of acetate and glycerol metabolism and likely favored the evolut...
Source: PLoS Genetics - November 6, 2009 Category: Genetics & Stem Cells Authors: Margie A. Kinnersley et al. Source Type: journals

OAZ-t/OAZ3 Is Essential for Rigid Connection of Sperm Tails to Heads in MouseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Polyamines are essential for cell proliferation and differentiation, but their role in these processes is unknown. Ornithine decarboxylase antizymes (OAZs) are enzymes that control the concentration of polyamines in cells. To elucidate the role of one of these enzymes, OAZ-t, in the regulation of polyamine concentration during sperm formation, we generated mutant mice in which the OAZ-t gene was disrupted. When we observed sperm from the mice lacking a functional Oaz-t gene, we found that the sperm heads separated easily from the tails, indicating that OAZ-t is essential for the formation of a rigid junctio...
Source: PLoS Genetics - November 6, 2009 Category: Genetics & Stem Cells Authors: Keizo Tokuhiro et al. Source Type: journals

The Sir2-Sum1 Complex Represses Transcription Using Both Promoter-Specific and Long-Range Mechanisms to Regulate Cell Identity and Sexual Cycle in the Yeast Kluyveromyces lactisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Sir2 deacetylases are found in organisms ranging from bacteria to mammals. Sir2 from the yeast Saccharomyces cerevisiae deacetylates histones and is part of the SIR complex that spreads across chromatin to repress gene expression. A related histone deacetylase, Hst1, interacts with a DNA–binding protein, Sum1, to repress genes in a promoter-specific manner. Hst1 and Sir2 are paralogs, arising from a duplication about 100 million years ago. To understand how Sir2 and Hst1 have diverged, as well as to investigate the evolutionary relationship between spreading and non-spreading mechanisms of gene repression...
Source: PLoS Genetics - November 6, 2009 Category: Genetics & Stem Cells Authors: Meleah A. Hickman et al. Source Type: journals

Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in DrosophilaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The fertilized animal embryo is a mass of uniform cells that becomes a complex, segmented, and highly organized structure of differentiated cells through the process of development. This vital process is controlled by networks of developmental genes interacting with each other on the molecular level. Because these genes are crucial for animal development, they are conserved both in function and at the DNA sequence level in related species. We have examined critical DNA sequence modules which regulate genes that pattern the early embryo in different species of the fruit fly. We found that despite rapid evolu...
Source: PLoS Genetics - November 6, 2009 Category: Genetics & Stem Cells Authors: Margaret C. W. Ho et al. Source Type: journals

Mutations in the Caenorhabditis elegans U2AF Large Subunit UAF-1 Alter the Choice of a 3′ Splice Site In VivoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Eukaryotic genes contain intervening intronic sequences that must be removed from pre-mRNA transcripts by RNA splicing to generate functional messenger RNAs. While studying genes that encode and control a presumptive muscle potassium channel complex in the nematode Caenorhabditis elegans, we found that mutations in two splicing factors, the U2AF large subunit and SF1/BBP suppress the rubberband Unc phenotype caused by a rare missense mutation in the gene unc-93. Mutations affecting the U2AF large subunit caused the recognition of a cryptic 3′ splice site generated by the unc-93 mutation, providing in vivo...
Source: PLoS Genetics - November 6, 2009 Category: Genetics & Stem Cells Authors: Long Ma et al. Source Type: journals

The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific ExonEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study investigates tissue-specific alternative splicing, which plays a key role in generating diversity in animal cells. We found a new testis-specific exon in a human homologue of the important Drosophila developmental regulator Groucho, which is activated by germ cell RNA binding proteins. By analyzing splicing control of this exon, we elucidated how variations in the activity and expression of splicing regulators together counterbalance splicing activation, and achieve more tightly regulated physiological splicing patterns. We find that although this new human testis-specific exon is not conserved in mice, it is fu...
Source: PLoS Genetics - November 6, 2009 Category: Genetics & Stem Cells Authors: Yilei Liu et al. Source Type: journals

Acquisition of Aneuploidy Provides Increased Fitness during the Evolution of Antifungal Drug ResistanceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary C. albicans, the most prevalent human fungal pathogen, acquires resistance to fluconazole by genetic alterations that often include changes in the number of chromosomes or chromosome arms (aneuploidy). Here we demonstrate that chromosomal rearrangements resulting in increased gene dosage are the predominant means of acquired resistance to the antifungal drug fluconazole in replicated experimental populations of C. albicans. A specific aneuploidy, isochromosome 5L, which is composed of two copies of the left arm of Chr5, occurs with high frequency and is detectable soon after fluconazole exposure. The early ...
Source: PLoS Genetics - October 30, 2009 Category: Genetics & Stem Cells Authors: Anna M. Selmecki et al. Source Type: journals

Progressive GAA·TTC Repeat Expansion in Human Cell LinesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The human genome is comprised of the DNA base sequences used by the cell as a blueprint to direct proper cellular function. Changes in this sequence, known as genomic instability, often interfere with vital cellular functions, resulting in genetic disorders. Repetitive DNA sequences are particularly susceptible to genomic instability. Trinucleotide repeat disorders are caused by three base repeat sequences that increase in size when passed from parent to child and during aging. Trinucleotide repeat expansion results in disease when the size of the repeat sequence increases into the pathogenic size range. Ou...
Source: PLoS Genetics - October 30, 2009 Category: Genetics & Stem Cells Authors: Scott Ditch et al. Source Type: journals

Dissection of the Complex Phenotype in Cuticular Mutants of Arabidopsis Reveals a Role of SERRATE as a MediatorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined whole-genome responses in these mutants and used an appropriate statistical procedure to reveal the genes which change their expression. We then applied the same approach to the analysis of hundreds of datasets in repositories. The comparison of gene expression profiles identified the gene SERRATE, which encodes a protein of RNA–processing multi-protein complexes, and further analysis revealed that the syndrome is suppressed in double mutants, as predicted. Our finding suggests that the mechanism which operates to control the integrity of the cuticle involves the regulation of small–RNA signaling. (Source: PLoS Genetics)
Source: PLoS Genetics - October 30, 2009 Category: Genetics & Stem Cells Authors: Derry Voisin et al. Source Type: journals

PLoS Genetics Issue Image | Vol. 5(10) October 2009Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Five-week-old juvenile gray mouse lemurs (Microcebus murinus) in a hollow tree in Kirindy Forest, Western Madagascar. Lemurs are the most distantly related non-human primates. A Research Article by Anne Averdam and colleagues in this issue of PLoS Genetics (see Averdam et al., 10.1371/journal.pgen.1000688) shows that lemurs differ considerably from "higher" primates in receptors of natural killer (NK) cells and their ligands. Instead of KIR or Ly49 genes, lemurs substantially expanded and diversified CD94/NKG2 receptors. Remarkably, this novel system of polymorphic and diverse receptors points to combinatorial diversity as...
Source: PLoS Genetics - October 30, 2009 Category: Genetics & Stem Cells Authors: PLoS Source Type: journals

Toward the Use of Genomics to Study Microevolutionary Change in BacteriaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bacteria evolve rapidly in response to the environment they encounter. Some environmental changes are experienced numerous times by bacteria from the same population, providing an opportunity to dissect the genetic basis of adaptive evolution. Here I discuss two examples in which the patterns of rapid change provide insight into medically important bacterial phenotypes, namely immune escape by Neisseria meningitidis and host specificity of Campylobacter jejuni. Genomic analysis of populations of bacteria from these species holds great promise but requires appropriate concepts and statistical tools. (Source: PLoS Genetics)
Source: PLoS Genetics - October 26, 2009 Category: Genetics & Stem Cells Authors: Daniel Falush Source Type: journals

The Key Role of Genomics in Modern Vaccine and Drug Design for Emerging Infectious DiseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It can be argued that the arrival of the “genomics era” has significantly shifted the paradigm of vaccine and therapeutics development from microbiological to sequence-based approaches. Genome sequences provide a previously unattainable route to investigate the mechanisms that underpin pathogenesis. Genomics, transcriptomics, metabolomics, structural genomics, proteomics, and immunomics are being exploited to perfect the identification of targets, to design new vaccines and drugs, and to predict their effects in patients. Furthermore, human genomics and related studies are providing insights into aspects of host biolog...
Source: PLoS Genetics - October 26, 2009 Category: Genetics & Stem Cells Authors: Kate L. Seib et al. Source Type: journals

Restricting Dosage Compensation Complex Binding to the X Chromosomes by H2A.Z/HTZ-1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary In organisms where females have two X chromosomes and males only have one, a mechanism called dosage compensation ensures that both sexes receive the same amount of information from their X chromosomes. Disruption of dosage compensation leads to lethality in the affected sex. While the precise mechanisms of dosage compensation differ between organisms, changes to the structure of the X chromosomes are involved in each case. The DNA of all chromosomes is packaged into a complex protein–DNA structure called chromatin. The most basic level of packaging involves wrapping DNA around a group of small proteins c...
Source: PLoS Genetics - October 23, 2009 Category: Genetics & Stem Cells Authors: Emily L. Petty et al. Source Type: journals

Loss of Yeast Peroxiredoxin Tsa1p Induces Genome Instability through Activation of the DNA Damage Checkpoint and Elevation of dNTP LevelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Peroxiredoxins are a family of antioxidant enzymes highly conserved from yeast to human. Loss of peroxiredoxin in mice can lead to severe anemia and malignant tumors, but the underlying cause is not understood. One way to derive new knowledge of peroxiredoxins is through genetic analysis in yeast. We have shown that loss of peroxiredoxins in yeast is associated with an increase in mutation rates. Here, we demonstrate that this elevation of mutation rates in yeast cells lacking a peroxiredoxin is due to increased production of deoxyribonucleoside triphosphates (dNTPs), the building blocks of DNA. Our finding...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Hei-Man Vincent Tang et al. Source Type: journals

Mouse HORMAD1 and HORMAD2, Two Conserved Meiotic Chromosomal Proteins, Are Depleted from Synapsed Chromosome Axes with the Help of TRIP13 AAA-ATPaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined the behaviour of meiotic mouse HORMA-domain proteins—HORMAD1 and HORMAD2—in wild-type and meiotic mutants. HORMAD1/2 preferentially accumulate on unsynapsed chromosome axes. Our data suggest that HORMAD1/2 depletion from chromosomes is a response to synaptonemal complex formation and it that is a conserved process supported by TRIP13/Pch2 AAA-ATPase. Assuming that HORMA-domain functions are conserved in mammals, we speculate that depletion of HORMADs from axes might contribute to the down-regulation of inter-homologue bias and the prophase checkpoint once homology search is completed and synaptonemal comple...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Lukasz Wojtasz et al. Source Type: journals

1+1 = 3: A Fusion of 2 Enzymes in the Methionine Salvage Pathway of Tetrahymena thermophila Creates a Trifunctional Enzyme That Catalyzes 3 Steps in the PathwayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Fusion genes, composed of the complete sequence of two or more other genes, are excellent markers of evolution. In addition, fused genes are usually composed of genes with related functions, which makes them useful in inferring function when the function of one of their components is known. We detected a fusion gene in the eukaryotic organism Tetrahymena thermophila that, although composed of only two genes, seems to perform the function of three genes in this organism. To show that this is the case, we expressed the Tetrahymena fused gene in three different yeast strains, each lacking one of these three ge...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Hannah M. W. Salim et al. Source Type: journals

Bruchpilot in Ribbon-Like Axonal Agglomerates, Behavioral Defects, and Early Death in SRPK79D Kinase Mutants of DrosophilaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Neurons communicate through release of neurotransmitters at specialized contacts called synapses. Modulation of synaptic transmission likely underlies all higher brain function including feature abstraction, learning and memory, and cognition. The complex molecular machinery that regulates neurotransmitter release has been conserved in evolution but is still incompletely understood. Using the genetic model organism Drosophila, we recently discovered a protein of the presynaptic ribbon (T-bar) that was called Bruchpilot (German for crash pilot) because flies with reduced amounts of this protein cannot fly. W...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Vanessa Nieratschker et al. Source Type: journals

Quantifying Adaptive Evolution in the Drosophila Immune SystemEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary All organisms are attacked by an ever-changing array of pathogens and parasites, and it is widely supposed that the ensuing host–parasite “arms race” must drive extensive adaptive evolution in genes of the immune system. Here we have taken advantage of new sequencing technologies and analytical approaches to quantify the amount of adaptation that is occurring in immunity genes relative to the rest of the genome. We sampled two species of fruit fly (D. melanogaster and D. simulans) from eight different populations around the world, and sequenced 136 immunity and 287 non-immunity genes from these sample...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Darren J. Obbard et al. Source Type: journals

High-Density SNP Screening of the Major Histocompatibility Complex in Systemic Lupus Erythematosus Demonstrates Strong Evidence for Independent Susceptibility RegionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and involvement of multiple organ systems. Although the cause of SLE remains unknown, several lines of evidence underscore the importance of genetic factors. As is true for most autoimmune diseases, a substantial genetic contribution to disease risk is conferred by major histocompatibility complex (MHC) gene(s) on chromosome 6. This region of the genome contains a large number of genes that participate in the immune response. However, the full contribution of this genomic region to SLE risk has not yet been ...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Lisa F. Barcellos et al. Source Type: journals

Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency DataEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The demographic history of our species is reflected in patterns of genetic variation within and among populations. We developed an efficient method for calculating the expected distribution of genetic variation, given a demographic model including such events as population size changes, population splits and joins, and migration. We applied our approach to publicly available human sequencing data, searching for models that best reproduce the observed patterns. Our joint analysis of data from African, European, and Asian populations yielded new dates for when these populations diverged. In particular, we fou...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Ryan N. Gutenkunst et al. Source Type: journals

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary A polymorphism of the INSIG2 gene was identified as being associated with obesity in one of the first genome-wide association studies. However, this association has since then been highly debated upon inconsistent subsequent reports. We collected association information from 34 studies including a total of 74,000 participants. In a meta-analysis of the 27 studies including 66,000 Caucasian adults, we found no overall association of this polymorphism rs7566605 with obesity, comparing subjects with a body-mass-index (BMI)≥30 kg/m2 with normal BMI subjects (BMI<30 kg/m2). Our data suggested an association...
Source: PLoS Genetics - October 22, 2009 Category: Genetics & Stem Cells Authors: Iris M. Heid et al. Source Type: journals

FON2 SPARE1 Redundantly Regulates Floral Meristem Maintenance with FLORAL ORGAN NUMBER2 in RiceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The body plan of plants is regulated by the function of apical meristems that are generated in the embryo. Leaves and floral organs are derived from cells supplied by stem cells in the vegetative shoot apical meristem (SAM) and the floral meristem (FM), respectively. Thus, genetic regulation of stem cell maintenance is a central issue in plant development. In the model plant Arabidopsis thaliana, CLAVATA3 (CLV3) functions as a key signaling molecule to restrict the size of the stem cell population in both the SAM and the FM. In rice, however, we show here that two CLV3-like genes, FLORAL ORGAN NUMBER2 (FON2...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Takuya Suzaki et al. Source Type: journals

Expression Quantitative Trait Loci Are Highly Sensitive to Cellular Differentiation StateEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Blood cell development from multipotent hematopoietic stem cells to specialized blood cells is accompanied by drastic changes in gene expression for which the triggers remain mostly unknown. Genetical genomics is an approach linking natural genetic variation to gene expression variation, thereby allowing the identification of genomic loci containing gene expression modulators (eQTLs). In this paper, we used a genetical genomics approach to analyze gene expression across four developmentally close blood cell types collected from a large number of genetically different but related mouse strains. We found that...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Alice Gerrits et al. Source Type: journals

Targeted Induction of Endoplasmic Reticulum Stress Induces Cartilage PathologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Mutations in genes for extracellular matrix proteins are generally thought to exert their pathogenic effects because of resulting defects in extracellular matrix. However, it is becoming increasingly clear that such mutations can also have significant effects inside the cell due to the induction of ER stress. Mutations in type X collagen cause a dwarfism called metaphyseal chondrodysplasia type Schmid. A gene targeted mouse model expressing mutant type X collagen exhibited an expanded hypertrophic zone of the growth plate and significant increases in cellular ER stress, as noted previously. VEGF expression ...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: M. Helen Rajpar et al. Source Type: journals

A Pol V–Mediated Silencing, Independent of RNA–Directed DNA Methylation, Applies to 5S rDNAEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary In plant genomes, the RNA–directed DNA methylation (RdDM) process induces de novo methylation of cytosines at repeated sequences. The RNA polymerases Pol IV and Pol V are two key components of the RdDM pathway. Pol IV acts with RDR2 (RNA–dependent RNA polymerase 2) and DCL3 (Dicer-Like protein 3) to generate short interfering RNAs (siRNAs). Pol V, in a partnership including AGO4 (Argonaute4) and DRM2 (Domains Rearranged Methyltransferase 2), drives DNA methylation at the targeted sequence. Changes in 5S (ribosomal DNA) rDNA methylation, 5S rDNA chromatin compaction, and 5S siRNA accumulation in Pol IV/V...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Julien Douet et al. Source Type: journals

A Novel Mechanism of Transposon-Mediated Gene ActivationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Transposons are “jumping genes” that can move from one location within a genome to another. Insertion of a transponson changes the DNA sequence and therefore gives rise to mutations that can activate or inactivate gene expression. Here, we demonstrate for the first time that one such transposon, Insertion Sequence 5 (IS5), when positioned upstream of a metabolic operon (glpFK) of E. coli, can activate the otherwise cryptic expression of the operon. This effect is due solely to a short region at the 3′ end of IS5 that harbors a permanent bend and an overlapping nucleoid protein binding site, both of wh...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Zhongge Zhang et al. Source Type: journals

A Novel System of Polymorphic and Diverse NK Cell Receptors in PrimatesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Most receptors of natural killer (NK) cells interact with highly polymorphic major histocompatibility complex (MHC) class I molecules and thereby regulate the activity of NK cells against infected or malignant target cells. Whereas humans, apes, and Old and New World monkeys use the family of killer cell immunoglobulin-like receptors (KIR) as highly diverse NK cell receptors, this function is performed in rodents by the diverse family of lectin-like receptors Ly49. When did this functional separation occur in evolution? We followed this by investigating lemurs, primates that are distantly related to humans....
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Anne Averdam et al. Source Type: journals

The Euchromatic and Heterochromatic Landscapes Are Shaped by Antagonizing Effects of Transcription on H2A.Z DepositionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary DNA in living cells is packaged into chromatin by histones and non-histone proteins. This packaging is very dynamic, allowing the controlled access of regulatory proteins such as transcription factors to DNA. Most chromatin is packaged with so-called canonical histones; namely H2A, H2B, H3, and H4. In some regions, however, variant histones replace canonical histones, creating special chromatin regions. Here we show that the variant histone H2A.Z is dynamically recruited to promoter regions where it helps in the recruitment of RNA polymerase II, the enzyme responsible for the first step of gene expression. ...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Sara Hardy et al. Source Type: journals

A Genealogical Interpretation of Principal Components AnalysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Genetic variation in natural populations typically demonstrates structure arising from diverse processes including geographical isolation, founder events, migration, and admixture. One technique commonly used to uncover such structure is principal components analysis, which identifies the primary axes of variation in data and projects the samples onto these axes in a graphically appealing and intuitive manner. However, as the method is non-parametric, it can be hard to relate PCA to underlying process. Here, I show that the underlying genealogical history of the samples can be related directly to the PC pro...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Gil McVean Source Type: journals

Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney AgingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Although family studies have shown that genes play a role in longevity, it has proven difficult to identify the specific genetic variants involved. We developed a sequential transcriptional profiling and eQTL mapping approach to find genes associated with aging in the kidney. First, we used genome-wide transcriptional profiling to determine which genes change expression with age in kidney tissue. Next, we used two methods to determine which of these age-regulated genes contain SNPs that associate with expression level. The allele-specific expression method, which compares the mRNA levels of the two alleles ...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Heather E. Wheeler et al. Source Type: journals

The Elongator Complex Interacts with PCNA and Modulates Transcriptional Silencing and Sensitivity to DNA Damage AgentsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary During S phase of the cell cycle, not only must DNA sequences be faithfully duplicated, chromatin structures must also be inherited into daughter cells to maintain gene expression states and cell identity. While significant progress has been made in understanding the regulation of DNA replication, how chromatin structures are maintained from one cell division cycle to the next (so-called epigenetic inheritance) is only partially understood. It is believed that the DNA replication-coupled nucleosome assembly process plays an important role in such inheritance as well as maintenance of genome stability. In th...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Qing Li et al. Source Type: journals

Limiting the Persistence of a Chromosome Break Diminishes Its Mutagenic PotentialEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary A deleterious lesion in DNA is a break of both strands, or a chromosome double-strand break (DSB). DSBs can arise during normal cellular metabolism, but are also a consequence of many forms of cancer therapy. If DSBs are not repaired prior to cell division, entire segments of a chromosome can be lost. Several pathways ensure that DSBs are repaired, though some pathways are prone to causing mutations and/or chromosomal rearrangements, each of which can contribute to cancer development. In the first part of this study, we describe the roles of individual genetic factors in distinct repair pathways of DSBs gen...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Nicole Bennardo et al. Source Type: journals

Acetylation by the Transcriptional Coactivator Gcn5 Plays a Novel Role in Co-Transcriptional Spliceosome AssemblyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Pre-messenger RNA splicing, the removal of non-coding RNA sequences (introns) that interrupt the protein-coding sequence of genes, is required for proper gene expression. While recent studies have revealed that intron recognition begins while the RNA is actively being synthesized by RNA polymerase II, little is known about how the proteins involved in gene transcription and RNA splicing interact to coordinate the two reactions. Here we show that the protein complex SAGA, which allows RNA polymerase II to navigate the three-dimensional structure of packaged DNA by acetylating histone proteins, has an additio...
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Felizza Q. Gunderson et al. Source Type: journals

On the Track of DNA Methylation: An Interview with Adrian BirdEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PLoS Genetics)
Source: PLoS Genetics - October 15, 2009 Category: Genetics & Stem Cells Authors: Jane Gitschier Source Type: journals

Plasticity of the Chemoreceptor Repertoire in Drosophila melanogasterEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Rapid adaptation and phenotypic plasticity to the chemical environment are essential prerequisites for survival; and, consequently, large families of genes that mediate the recognition of olfactory and gustatory cues have evolved. We asked how flexible the expression of these genes is in the face of rapidly changing conditions encountered during an individual's lifetime. We used the fruit fly, Drosophila melanogaster, to address this question, since both the genetic composition and environmental rearing conditions can be controlled precisely in this experimentally amenable model organism. By measuring expre...
Source: PLoS Genetics - October 8, 2009 Category: Genetics & Stem Cells Authors: Shanshan Zhou et al. Source Type: journals

p63 and p73 Transcriptionally Regulate Genes Involved in DNA RepairEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary p63 and p73 have been identified as important suppressors of tumorigenesis and metastasis. Although they are structurally similar to p53, they have many functions that are unique including roles in development and metastasis. Here we show, using a genome-wide analysis of cells lacking p63 and p73 individually and in combination, that p63 and p73 regulate many unique target genes involved in multiple cellular processes. Interestingly, one of these pathways is DNA repair. Further validation of differentially expressed target genes in this pathway, revealed that p63 and p73 transcriptionally regulate BRCA2, Ra...
Source: PLoS Genetics - October 8, 2009 Category: Genetics & Stem Cells Authors: Yu-Li Lin et al. Source Type: journals

Caenorhabditis elegans Myotubularin MTM-1 Negatively Regulates the Engulfment of Apoptotic CellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we found that MTM-1 inhibits cell corpse engulfment through a series of evolutionarily conserved signaling molecules (the bipartite GEF (CED-5/DOCK180-CED-12/ELMO) and the GTPase CED-10/Rac). The negative regulatory effect of MTM-1 requires both its lipid phosphatase activity and the function of another group of enzymes called PI3-kinases. We propose that MTM-1 acts through Rac GTPase CED-10 by dephosphorylating the lipid PtdIns(3)P on the plasma membrane. We have identified a negative regulatory mechanism of cell corpse engulfment and a previously unknown cellular function of MTM-1, which may provide furthe...
Source: PLoS Genetics - October 8, 2009 Category: Genetics & Stem Cells Authors: Wei Zou et al. Source Type: journals

From Disease Association to Risk Assessment: An Optimistic View from Genome-Wide Association Studies on Type 1 DiabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary An often touted utility of genome-wide association studies (GWAS) is that the resulting discoveries can facilitate implementation of personalized medicine, in which preventive and therapeutic interventions for complex diseases can be tailored to individual genetic profiles. However, recent studies using whole-genome SNP genotype data for disease risk assessment have generally failed to achieve satisfactory results, leading to a pessimistic view of the utility of genotype data for such purposes. Here we propose that sophisticated machine-learning approaches on a large ensemble of markers, which contain both ...
Source: PLoS Genetics - October 8, 2009 Category: Genetics & Stem Cells Authors: Zhi Wei et al. Source Type: journals

Life on Arginine for Mycoplasma hominis: Clues from Its Minimal Genome and Comparison with Other Human Urogenital MycoplasmasEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study provides insight for the synthesis of artificial genomes. (Source: PLoS Genetics)
Source: PLoS Genetics - October 8, 2009 Category: Genetics & Stem Cells Authors: Sabine Pereyre et al. Source Type: journals

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric CancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Gastric cancer is the second leading cause of global cancer mortality. With current treatments, less than a quarter of patients survive longer than five years after surgery. Individual gastric cancers are highly disparate in their cellular characteristics and responses to standard chemotherapeutic drugs, making gastric cancer a complex disease. Pathway based approaches, rather than single gene studies, may help to unravel this complexity. Here, we make use of a computational approach to identify connections between molecular pathways and cancer profiles. In a large scale study of more than 300 patients, we ...
Source: PLoS Genetics - October 1, 2009 Category: Genetics & Stem Cells Authors: Chia Huey Ooi et al. Source Type: journals

Requirements for F-BAR Proteins TOCA-1 and TOCA-2 in Actin Dynamics and Membrane Trafficking during Caenorhabditis elegans Oocyte Growth and Embryonic Epidermal MorphogenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Cells continuously remodel their shape especially during cell migration, differentiation, and tissues morphogenesis. This occurs through the dynamic reorganization of their plasma membrane and actin cytoskeleton: two processes that must therefore be intimately linked and coordinated. Molecules that sit at the crossroads of membrane remodeling and actin dynamics are predicted to play a pivotal role in coordinating these processes. The TOCA family of proteins represents a case in point. These proteins bind to and deform membranes during processes such as membrane trafficking. They also control actin dynamics ...
Source: PLoS Genetics - October 1, 2009 Category: Genetics & Stem Cells Authors: Chiara Giuliani et al. Source Type: journals