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 'Genetics' source. Mon, 06 Feb 2012 09:32:10 +0100 http://www.medworm.com/index.php?rid=5590831&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F51%3Frss%3D1 Studies of the processes leading to the construction of a bud and its separation from the mother cell in Saccharomyces cerevisiae have provided foundational paradigms for the mechanisms of polarity establishment, cytoskeletal organization, and cytokinesis. Here we review our current understanding of how these morphogenetic events occur and how they are controlled by the cell-cycle-regulatory cyclin-CDK system. In addition, defects in morphogenesis provide signals that feed back on the cyclin-CDK system, and we review what is known regarding regulation of cell-cycle progression in response to such defects, primarily acting through the kinase Swe1p. The bidirectional communication between morphogenesis and the cell cycle is crucial for successful proliferation, and its study has illuminated ... Genetics journals http://www.medworm.com/rss/comments.php?id=5590831 Wed, 04 Jan 2012 05:00:00 +0100 5590831 http://www.medworm.com/index.php?rid=5567060&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F283%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5567060 Wed, 04 Jan 2012 05:00:00 +0100 5567060 http://www.medworm.com/index.php?rid=5567059&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F279%3Frss%3D1 Drosophila polyhomeotic (ph) is one of the important polycomb group genes that is linked to human cancer. In the mosaic eye imaginal discs, while phdel, a null allele, causes only non-autonomous overgrowth, ph505, a hypomorphic allele, causes both autonomous and non-autonomous overgrowth. These allele-specific phenotypes stem from the different sensitivities of ph mutant cells to the Upd homologs that they secrete. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5567059 Wed, 04 Jan 2012 05:00:00 +0100 5567059 http://www.medworm.com/index.php?rid=5567058&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F275%3Frss%3D1 A strategy to reduce computational demands of genome-wide association studies fitting a mixed model is presented. Improvements are achieved by utilizing a large proportion of calculations that remain constant across the multiple analyses for individual markers involved, with estimates obtained without inverting large matrices. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5567058 Wed, 04 Jan 2012 05:00:00 +0100 5567058 http://www.medworm.com/index.php?rid=5567057&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F263%3Frss%3D1 The environment can have a decisive influence on the structure of the genome, changing it in a certain direction. Therefore, the genomic distribution of environmentally sensitive transposable elements may vary measurably across a species area. In the present research, we aimed to detect and evaluate the level of LTR retrotransposon intraspecific variability in Aegilops speltoides (2n = 2x = 14), a wild cross-pollinated relative of cultivated wheat. The interretrotransposon amplified polymorphism (IRAP) protocol was applied to detect and evaluate the level of retrotransposon intraspecific variability in Ae. speltoides and closely related species. IRAP analysis revealed significant diversity in TE distribution. Various genotypes from the 13 explored populations significantly differ with resp... Genetics journals http://www.medworm.com/rss/comments.php?id=5567057 Wed, 04 Jan 2012 05:00:00 +0100 5567057 http://www.medworm.com/index.php?rid=5567056&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F251%3Frss%3D1 Transcription factors and their binding sites have been proposed as primary targets of evolutionary adaptation because changes to single transcription factors can lead to far-reaching changes in gene expression patterns. Nevertheless, there is very little concrete evidence for such evolutionary changes. Industrial wine yeast strains, of the species Saccharomyces cerevisiae, are a geno- and phenotypically diverse group of organisms that have adapted to the ecological niches of industrial winemaking environments and have been selected to produce specific styles of wine. Variation in transcriptional regulation among wine yeast strains may be responsible for many of the observed differences and specific adaptations to different fermentative conditions in the context of commercial winemaking. W... Genetics journals http://www.medworm.com/rss/comments.php?id=5567056 Wed, 04 Jan 2012 05:00:00 +0100 5567056 http://www.medworm.com/index.php?rid=5567055&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F231%3Frss%3D1 Bayesian hierarchical shrinkage methods have been widely used for quantitative trait locus mapping. From the computational perspective, the application of the Markov chain Monte Carlo (MCMC) method is not optimal for high-dimensional problems such as the ones arising in epistatic analysis. Maximum a posteriori (MAP) estimation can be a faster alternative, but it usually produces only point estimates without providing any measures of uncertainty (i.e., interval estimates). The variational Bayes method, stemming from the mean field theory in theoretical physics, is regarded as a compromise between MAP and MCMC estimation, which can be efficiently computed and produces the uncertainty measures of the estimates. Furthermore, variational Bayes methods can be regarded as the extension of traditi... Genetics journals http://www.medworm.com/rss/comments.php?id=5567055 Wed, 04 Jan 2012 05:00:00 +0100 5567055 http://www.medworm.com/index.php?rid=5567054&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F217%3Frss%3D1 To model deviations from selectively neutral genetic variation caused by different forms of selection, it is necessary to first understand patterns of neutral variation. Best understood is neutral genetic variation at a single locus. But, as is well known, additional insights can be gained by investigating multiple loci. The resulting patterns reflect the degree of association (linkage) between loci and provide information about the underlying multilocus gene genealogies. The statistical properties of two-locus gene genealogies have been intensively studied for populations of constant size, as well as for simple demographic histories such as exponential population growth and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poor... Genetics journals http://www.medworm.com/rss/comments.php?id=5567054 Wed, 04 Jan 2012 05:00:00 +0100 5567054 http://www.medworm.com/index.php?rid=5567053&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F203%3Frss%3D1 Spatially varying selection on a given polymorphism is expected to produce a localized peak in the between-population component of nucleotide diversity, and theory suggests that the chromosomal extent of elevated differentiation may be enhanced in cases where tandemly linked genes contribute to fitness variation. An intriguing example is provided by the tandemly duplicated β-globin genes of deer mice (Peromyscus maniculatus), which contribute to adaptive differentiation in blood–oxygen affinity between high- and low-altitude populations. Remarkably, the two β-globin genes segregate the same pair of functionally distinct alleles due to a history of interparalog gene conversion and alleles of the same functional type are in perfect coupling-phase linkage disequilibrium (LD). ... Genetics journals http://www.medworm.com/rss/comments.php?id=5567053 Wed, 04 Jan 2012 05:00:00 +0100 5567053 http://www.medworm.com/index.php?rid=5567052&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F187%3Frss%3D1 Estimates of the coalescent effective population size Ne can be poorly correlated with the true population size. The relationship between Ne and the population size is sensitive to the way in which birth and death rates vary over time. The problem of inference is exacerbated when the mechanisms underlying population dynamics are complex and depend on many parameters. In instances where nonparametric estimators of Ne such as the skyline struggle to reproduce the correct demographic history, model-based estimators that can draw on prior information about population size and growth rates may be more efficient. A coalescent model is developed for a large class of populations such that the demographic history is described by a deterministic nonlinear dynamical system of arbitrary dimension. Thi... Genetics journals http://www.medworm.com/rss/comments.php?id=5567052 Wed, 04 Jan 2012 05:00:00 +0100 5567052 http://www.medworm.com/index.php?rid=5567051&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F175%3Frss%3D1 Measuring fitness with precision is a key issue in evolutionary biology, particularly in studying mutations of small effects. It is usually thought that sampling error and drift prevent precise measurement of very small fitness effects. We circumvented these limits by using a new combined approach to measuring and analyzing fitness. We estimated the mutational fitness effect (MFE) of three independent mini-Tn10 transposon insertion mutations by conducting competition experiments in large populations of Escherichia coli under controlled laboratory conditions. Using flow cytometry to assess genotype frequencies from very large samples alleviated the problem of sampling error, while the effect of drift was controlled by using large populations and massive replication of fitness measures. Furt... Genetics journals http://www.medworm.com/rss/comments.php?id=5567051 Wed, 04 Jan 2012 05:00:00 +0100 5567051 http://www.medworm.com/index.php?rid=5567050&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F159%3Frss%3D1 High-throughput genotyping and sequencing technologies can generate dense sets of genetic markers for large numbers of individuals. For most species, these data will contain many markers in linkage disequilibrium (LD). To utilize such data for population structure inference, we investigate the use of haplotypes constructed by combining the alleles at single-nucleotide polymorphisms (SNPs). We introduce a statistic derived from information theory, the gain of informativeness for assignment (GIA), which quantifies the additional information for assigning individuals to populations using haplotype data compared to using individual loci separately. Using a two-loci–two-allele model, we demonstrate that combining markers in linkage equilibrium into haplotypes always leads to nonpositive G... Genetics journals http://www.medworm.com/rss/comments.php?id=5567050 Wed, 04 Jan 2012 05:00:00 +0100 5567050 http://www.medworm.com/index.php?rid=5567049&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F143%3Frss%3D1 Sperm from different species have evolved distinctive motility structures, including tubulin-based flagella in mammals and major sperm protein (MSP)-based pseudopods in nematodes. Despite such divergence, we show that sperm-specific PP1 phosphatases, which are required for male fertility in mouse, function in multiple processes in the development and motility of Caenorhabditis elegans amoeboid sperm. We used live-imaging analysis to show the PP1 phosphatases GSP-3 and GSP-4 (GSP-3/4) are required to partition chromosomes during sperm meiosis. Postmeiosis, tracking fluorescently labeled sperm revealed that both male and hermaphrodite sperm lacking GSP-3/4 are immotile. Genetic and in vitro activation assays show lack of GSP-3/4 causes defects in pseudopod development and the rate of pseudop... Genetics journals http://www.medworm.com/rss/comments.php?id=5567049 Wed, 04 Jan 2012 05:00:00 +0100 5567049 http://www.medworm.com/index.php?rid=5567048&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F129%3Frss%3D1 The cytoskeleton regulator UNC-53/NAV2 is required for both the anterior and posterior outgrowth of several neurons as well as that of the excretory cell while the kinesin-like motor VAB-8 is essential for most posteriorly directed migrations in Caenorhabditis elegans. Null mutations in either unc-53 or vab-8 result in reduced posterior excretory canal outgrowth, while double null mutants display an enhanced canal extension defect, suggesting the genes act in separate pathways to control this posteriorly directed outgrowth. Genetic analysis of putative interactors of UNC-53 or VAB-8, and cell-specific rescue experiments suggest that VAB-8, SAX-3/ROBO, SLT-1/Slit, and EVA-1 are functioning together in the outgrowth of the excretory canals, while UNC-53 appears to function in a parallel path... Genetics journals http://www.medworm.com/rss/comments.php?id=5567048 Wed, 04 Jan 2012 05:00:00 +0100 5567048 http://www.medworm.com/index.php?rid=5567047&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F113%3Frss%3D1 We report here the use of a comparative genomics approach to identify seven candidate polymorphic genes associated with four vegetative incompatibility (vic) loci of the chestnut blight fungus Cryphonectria parasitica. Disruption of candidate alleles in one of two strains that were heteroallelic at vic2, vic6, or vic7 resulted in enhanced virus transmission, but did not prevent barrage formation associated with mycelial incompatibility. Detailed characterization of the vic6 locus revealed the involvement of nonallelic interactions between two tightly linked genes in barrage formation, heterokaryon formation, and asymmetric, gene-specific influences on virus transmission. The combined results establish molecular identities of genes associated with four C. parasitica vic loci and provide ins... Genetics journals http://www.medworm.com/rss/comments.php?id=5567047 Wed, 04 Jan 2012 05:00:00 +0100 5567047 http://www.medworm.com/index.php?rid=5567046&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F101%3Frss%3D1 Adherence to host cells is an important step in the pathogenicity of the opportunistic fungal pathogen Candida glabrata. This adherence is mediated by some members of the large family of cell wall proteins encoded by the EPA (Epithelial Adhesin) genes present in the C. glabrata genome. The majority of the EPA genes are localized close to different telomeres in C. glabrata, resulting in a negative regulation of transcription of these genes through chromatin-based subtelomeric silencing. In vitro, adherence to epithelial cells is mainly mediated by Epa1, the only member of the EPA family that is expressed in vitro. EPA1 forms a cluster with EPA2 and EPA3 at the subtelomeric region of telomere E-R. EPA2 and EPA3 are subject to silencing that propagates from this telomere in a process that dep... Genetics journals http://www.medworm.com/rss/comments.php?id=5567046 Wed, 04 Jan 2012 05:00:00 +0100 5567046 http://www.medworm.com/index.php?rid=5567045&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F91%3Frss%3D1 We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a "global" or general H3K4 di- and trimethyl HMT in Drosophila. Levels of H3K4 di- and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity o... Genetics journals http://www.medworm.com/rss/comments.php?id=5567045 Wed, 04 Jan 2012 05:00:00 +0100 5567045 http://www.medworm.com/index.php?rid=5567044&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F79%3Frss%3D1 Salmonella enterica serovar Typhimurium uses the Salmonella pathogenicity island 1 (SPI1) type III secretion system to induce inflammatory diarrhea and bacterial uptake into intestinal epithelial cells. The expression of hilA, encoding the transcriptional activator of the SPI1 structural genes, is directly controlled by three AraC-like regulators, HilD, HilC, and RtsA, each of which can activate the hilD, hilC, rtsA, and hilA genes, forming a complex feed-forward regulatory loop. A large number of factors and environmental signals have been implicated in SPI1 regulation. We have developed a series of genetic tests that allows us to determine where these factors feed into the SPI1 regulatory circuit. Using this approach, we have grouped 21 of the known SPI1 regulators and environmental sign... Genetics journals http://www.medworm.com/rss/comments.php?id=5567044 Wed, 04 Jan 2012 05:00:00 +0100 5567044 http://www.medworm.com/index.php?rid=5567043&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F51%3Frss%3D1 Studies of the processes leading to the construction of a bud and its separation from the mother cell in Saccharomyces cerevisiae have provided foundational paradigms for the mechanisms of polarity establishment, cytoskeletal organization, and cytokinesis. Here we review our current understanding of how these morphogenetic events occur and how they are controlled by the cell-cycle-regulatory cyclin-CDK system. In addition, defects in morphogenesis provide signals that feed back on the cyclin-CDK system, and we review what is known regarding regulation of cell-cycle progression in response to such defects, primarily acting through the kinase Swe1p. The bidirectional communication between morphogenesis and the cell cycle is crucial for successful proliferation, and its study has illuminated ... Genetics journals http://www.medworm.com/rss/comments.php?id=5567043 Wed, 04 Jan 2012 05:00:00 +0100 5567043 http://www.medworm.com/index.php?rid=5567042&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F23%3Frss%3D1 Filamentous growth is a nutrient-regulated growth response that occurs in many fungal species. In pathogens, filamentous growth is critical for host–cell attachment, invasion into tissues, and virulence. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth, which provides a genetically tractable system to study the molecular basis of the response. Filamentous growth is regulated by evolutionarily conserved signaling pathways. One of these pathways is a mitogen activated protein kinase (MAPK) pathway. A remarkable feature of the filamentous growth MAPK pathway is that it is composed of factors that also function in other pathways. An intriguing challenge therefore has been to understand how pathways that share components establish and maintain their identity. Other ... Genetics journals http://www.medworm.com/rss/comments.php?id=5567042 Wed, 04 Jan 2012 05:00:00 +0100 5567042 http://www.medworm.com/index.php?rid=5567041&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F5%3Frss%3D1 The process of evolution at a given site in the genome can be influenced by the action of selection at other sites, especially when these are closely linked to it. Such selection reduces the effective population size experienced by the site in question (the Hill–Robertson effect), reducing the level of variability and the efficacy of selection. In particular, deleterious variants are continually being produced by mutation and then eliminated by selection at sites throughout the genome. The resulting reduction in variability at linked neutral or nearly neutral sites can be predicted from the theory of background selection, which assumes that deleterious mutations have such large effects that their behavior in the population is effectively deterministic. More weakly selected mutations ... Genetics journals http://www.medworm.com/rss/comments.php?id=5567041 Wed, 04 Jan 2012 05:00:00 +0100 5567041 http://www.medworm.com/index.php?rid=5567040&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2F1%3Frss%3D1 The readers of this journal may well be aware of Professor Crow’s scientific achievements and his role as the editor of Perspectives. In addition, for many thousands of students at the University of Wisconsin over many generations, James F. Crow was one of the most memorable teachers at both the undergraduate and graduate levels. What is less known is his major role in public service where he served as chair of many important committees for the National Academy of Sciences, the National Institutes of Health, the National Institutes of Justice as well as various international programs. In all of these efforts, Professor Crow has left a lasting impact. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5567040 Wed, 04 Jan 2012 05:00:00 +0100 5567040 http://www.medworm.com/index.php?rid=5567039&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F190%2F1%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5567039 Wed, 04 Jan 2012 05:00:00 +0100 5567039 http://www.medworm.com/index.php?rid=5510648&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1527%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5510648 Thu, 15 Dec 2011 05:00:00 +0100 5510648 http://www.medworm.com/index.php?rid=5510647&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1525%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5510647 Thu, 15 Dec 2011 05:00:00 +0100 5510647 http://www.medworm.com/index.php?rid=5510646&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1515%3Frss%3D1 Seed dormancy has been associated with red grain color in cereal crops for a century. The association was linked to qSD7-1/qPC7, a cluster of quantitative trait loci for seed dormancy/pericarp color in weedy red rice. This research delimited qSD7-1/qPC7 to the Os07g11020 or Rc locus encoding a basic helix-loop-helix family transcription factor by intragenic recombinants and provided unambiguous evidence that the association arises from pleiotropy. The pleiotropic gene expressed in early developing seeds promoted expression of key genes for biosynthesis of abscisic acid (ABA), resulting in an increase in accumulation of the dormancy-inducing hormone; activated a conserved network of eight genes for flavonoid biosynthesis to produce the pigments in the lower epidermal cells of the pericarp t... Genetics journals http://www.medworm.com/rss/comments.php?id=5510646 Thu, 15 Dec 2011 05:00:00 +0100 5510646 http://www.medworm.com/index.php?rid=5510645&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1497%3Frss%3D1 In genome-wide association studies hundreds of thousands of loci are scanned in thousands of cases and controls, with the goal of identifying genomic loci underpinning disease. This is a challenging statistical problem requiring strong evidence. Only a small proportion of the heritability of common diseases has so far been explained. This "dark matter of the genome" is a subject of much discussion. It is critical to have experimental design criteria that ensure that associations between genomic loci and phenotypes are robustly detected. To ensure associations are robustly detected we require good power (e.g., 0.8) and sufficiently strong evidence [i.e., a high Bayes factor (e.g., 106, meaning the data are 1 million times more likely if the association is real than if there is no associatio... Genetics journals http://www.medworm.com/rss/comments.php?id=5510645 Thu, 15 Dec 2011 05:00:00 +0100 5510645 http://www.medworm.com/index.php?rid=5510644&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1487%3Frss%3D1 Individuals with full or partial Trisomy 21 (Ts21) present with clinical features collectively referred to as Down syndrome (DS), although DS phenotypes vary in incidence and severity between individuals. Differing genetic and phenotypic content in individuals with DS as well as mouse models of DS facilitate the understanding of the correlation between specific genes and phenotypes associated with Ts21. The Ts1Rhr mouse model is trisomic for 33 genes (the "Down syndrome critical region" or DSCR) hypothesized to be responsible for many clinical DS features, including craniofacial dysmorphology with a small mandible. Experiments with Ts1Rhr mice showed that the DSCR was not sufficient to cause all DS phenotypes by identifying uncharacteristic craniofacial abnormalities not found in individua... Genetics journals http://www.medworm.com/rss/comments.php?id=5510644 Thu, 15 Dec 2011 05:00:00 +0100 5510644 http://www.medworm.com/index.php?rid=5510643&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1473%3Frss%3D1 Inbreeding depression and genetic load have been widely observed, but their genetic basis and effects on fitness during the life cycle remain poorly understood, especially for marine animals with high fecundity and high, early mortality (type-III survivorship). A high load of recessive mutations was previously inferred for the Pacific oyster Crassostrea gigas, from massive distortions of zygotic, marker segregation ratios in F2 families. However, the number, genomic location, and stage-specific onset of mutations affecting viability have not been thoroughly investigated. Here, we again report massive distortions of microsatellite-marker segregation ratios in two F2 hybrid families, but we now locate the causative deleterious mutations, using a quantitative trait locus (QTL) interval-mappin... Genetics journals http://www.medworm.com/rss/comments.php?id=5510643 Thu, 15 Dec 2011 05:00:00 +0100 5510643 http://www.medworm.com/index.php?rid=5510642&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1461%3Frss%3D1 The frequency and character of interactions among genes influencing complex traits remain unknown. Our ignorance is most acute for segregating variation within natural populations, the epistasis most relevant for quantitative trait evolution. Here, we report a comprehensive survey of interactions among a defined set of flower-size QTL: loci polymorphic within a single natural population of yellow monkeyflower (Mimulus guttatus). We find that epistasis is typical. Observed phenotypes routinely differ from those predicted on the basis of direct allelic affects in the isogenic background, although the direction of deviations is highly variable. Across QTL pairs, there are significantly positive and negative interactions for every trait. Across traits, specific locus pairs routinely exhibit bo... Genetics journals http://www.medworm.com/rss/comments.php?id=5510642 Thu, 15 Dec 2011 05:00:00 +0100 5510642 http://www.medworm.com/index.php?rid=5510641&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1449%3Frss%3D1 High-throughput genomics allows genome-wide quantification of gene expression levels in tissues and cell types and, when combined with sequence variation data, permits the identification of genetic control points of expression (expression QTL or eQTL). Clusters of eQTL influenced by single genetic polymorphisms can inform on hotspots of regulation of pathways and networks, although very few hotspots have been robustly detected, replicated, or experimentally verified. Here we present a novel modeling strategy to estimate the propensity of a genetic marker to influence several expression traits at the same time, based on a hierarchical formulation of related regressions. We implement this hierarchical regression model in a Bayesian framework using a stochastic search algorithm, HESS, that ef... Genetics journals http://www.medworm.com/rss/comments.php?id=5510641 Thu, 15 Dec 2011 05:00:00 +0100 5510641 http://www.medworm.com/index.php?rid=5510640&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1439%3Frss%3D1 Variation in rates of molecular evolution has been attributed to numerous, interrelated causes, including metabolic rate, body size, and generation time. Speculation concerning the influence of metabolic rate on rates of evolution often invokes the putative mutagenic effects of oxidative stress. To isolate the effects of oxidative stress on the germline from the effects of metabolic rate, generation time, and other factors, we allowed mutations to accumulate under relaxed selection for 125 generations in two strains of the nematode Caenorhabditis elegans, the canonical wild-type strain (N2) and a mutant strain with elevated steady-state oxidative stress (mev-1). Contrary to our expectation, the mutational decline in fitness did not differ between N2 and mev-1. This result suggests that the... Genetics journals http://www.medworm.com/rss/comments.php?id=5510640 Thu, 15 Dec 2011 05:00:00 +0100 5510640 http://www.medworm.com/index.php?rid=5510639&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1427%3Frss%3D1 The distribution of fitness effects (DFE) of new mutations is of fundamental importance in evolutionary genetics. Recently, methods have been developed for inferring the DFE that use information from the allele frequency distributions of putatively neutral and selected nucleotide polymorphic variants in a population sample. Here, we extend an existing maximum-likelihood method that estimates the DFE under the assumption that mutational effects are unconditionally deleterious, by including a fraction of positively selected mutations. We allow one or more classes of positive selection coefficients in the model and estimate both the fraction of mutations that are advantageous and the strength of selection acting on them. We show by simulations that the method is capable of recovering the para... Genetics journals http://www.medworm.com/rss/comments.php?id=5510639 Thu, 15 Dec 2011 05:00:00 +0100 5510639 http://www.medworm.com/index.php?rid=5510638&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1413%3Frss%3D1 Admixed populations have been used for inferring migrations, detecting natural selection, and finding disease genes. These applications often use a simple statistical model of admixture rather than a modeling perspective that incorporates a more realistic history of the admixture process. Here, we develop a general model of admixture that mechanistically accounts for complex historical admixture processes. We consider two source populations contributing to the ancestry of a hybrid population, potentially with variable contributions across generations. For a random individual in the hybrid population at a given point in time, we study the fraction of genetic admixture originating from a specific one of the source populations by computing its moments as functions of time and of introgression... Genetics journals http://www.medworm.com/rss/comments.php?id=5510638 Thu, 15 Dec 2011 05:00:00 +0100 5510638 http://www.medworm.com/index.php?rid=5510637&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1403%3Frss%3D1 The rate of microsatellite mutation is dependent upon both the allele length and the repeat motif, but the exact nature of this relationship is still unknown. We analyzed data on the inheritance of human Y-chromosomal microsatellites in father–son duos, taken from 24 published reports and comprising 15,285 directly observable meioses. At the six microsatellites analyzed (DYS19, DYS389I, DYS390, DYS391, DYS392, and DYS393), a total of 162 mutations were observed. For each locus, we employed a maximum-likelihood approach to evaluate one of several single-step mutation models on the basis of the data. For five of the six loci considered, a novel logistic mutation model was found to provide the best fit according to Akaike’s information criterion. This implies that the mutation pro... Genetics journals http://www.medworm.com/rss/comments.php?id=5510637 Thu, 15 Dec 2011 05:00:00 +0100 5510637 http://www.medworm.com/index.php?rid=5510636&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1389%3Frss%3D1 The effective population size (Ne) is one of the most fundamental parameters in population genetics. It is thought to vary across the genome as a consequence of differences in the rate of recombination and the density of selected sites due to the processes of genetic hitchhiking and background selection. Although it is known that there is intragenomic variation in the effective population size in some species, it is not known whether this is widespread or how much variation in the effective population size there is. Here, we test whether the effective population size varies across the genome, between protein-coding genes, in 10 eukaryotic species by considering whether there is significant variation in neutral diversity, taking into account differences in the mutation rate between loci by ... Genetics journals http://www.medworm.com/rss/comments.php?id=5510636 Thu, 15 Dec 2011 05:00:00 +0100 5510636 http://www.medworm.com/index.php?rid=5510635&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1377%3Frss%3D1 Genome-wide association studies have thus far failed to explain the observed heritability of complex human diseases. This is referred to as the "missing heritability" problem. However, these analyses have usually neglected to consider a role for epigenetic variation, which has been associated with many human diseases. We extend models of epigenetic inheritance to investigate whether environment-sensitive epigenetic modifications of DNA might explain observed patterns of familial aggregation. We find that variation in epigenetic state and environmental state can result in highly heritable phenotypes through a combination of epigenetic and environmental inheritance. These two inheritance processes together can produce familial covariances significantly higher than those predicted by models o... Genetics journals http://www.medworm.com/rss/comments.php?id=5510635 Thu, 15 Dec 2011 05:00:00 +0100 5510635 http://www.medworm.com/index.php?rid=5510634&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1361%3Frss%3D1 In nonrecombining genomes, genetic linkage can be an important evolutionary force. Linkage generates interference interactions, by which simultaneously occurring mutations affect each other’s chance of fixation. Here, we develop a comprehensive model of adaptive evolution in linked genomes, which integrates interference interactions between multiple beneficial and deleterious mutations into a unified framework. By an approximate analytical solution, we predict the fixation rates of these mutations, as well as the probabilities of beneficial and deleterious alleles at fixed genomic sites. We find that interference interactions generate a regime of emergent neutrality: all genomic sites with selection coefficients smaller in magnitude than a characteristic threshold have nearly random ... Genetics journals http://www.medworm.com/rss/comments.php?id=5510634 Thu, 15 Dec 2011 05:00:00 +0100 5510634 http://www.medworm.com/index.php?rid=5510633&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1347%3Frss%3D1 Genetic selection is a major force shaping life on earth. In classical genetic theory, response to selection is the product of the strength of selection and the additive genetic variance in a trait. The additive genetic variance reflects a population’s intrinsic potential to respond to selection. The ordinary additive genetic variance, however, ignores the social organization of life. With social interactions among individuals, individual trait values may depend on genes in others, a phenomenon known as indirect genetic effects. Models accounting for indirect genetic effects, however, lack a general definition of heritable variation. Here I propose a general definition of the heritable variation that determines the potential of a population to respond to selection. This generalizes t... Genetics journals http://www.medworm.com/rss/comments.php?id=5510633 Thu, 15 Dec 2011 05:00:00 +0100 5510633 http://www.medworm.com/index.php?rid=5510632&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1341%3Frss%3D1 Mating behavior of animals is regulated by the sensory stimuli provided by the other sex. Sexually receptive females emit mating signals that can be inhibited by male ejaculate. The genetic mechanisms controlling the release of mating signals and encoding behavioral responses remain enigmatic. Here we present evidence of a Caenorhabditis elegans hermaphrodite-derived cue that stimulates male mating-response behavior and is dynamically regulated by her reproductive status. Wild-type males preferentially mated with older hermaphrodites. Increased sex appeal of older hermaphrodites was potent enough to stimulate robust response from mating-deficient pkd-2 and lov-1 polycystin mutant males. This enhanced response of pkd-2 males toward older hermaphrodites was independent of short-chain ascaros... Genetics journals http://www.medworm.com/rss/comments.php?id=5510632 Thu, 15 Dec 2011 05:00:00 +0100 5510632 http://www.medworm.com/index.php?rid=5510631&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1327%3Frss%3D1 Many animals sense environmental gases such as carbon dioxide and oxygen using specialized populations of gas-sensing neurons. The proper development and function of these neurons is critical for survival, as the inability to respond to changes in ambient carbon dioxide and oxygen levels can result in reduced neural activity and ultimately death. Despite the importance of gas-sensing neurons for survival, little is known about the developmental programs that underlie their formation. Here we identify the ETS-family transcription factor ETS-5 as critical for the normal differentiation of the carbon dioxide-sensing BAG neurons in Caenorhabditis elegans. Whereas wild-type animals show acute behavioral avoidance of carbon dioxide, ets-5 mutant animals do not respond to carbon dioxide. The ets-... Genetics journals http://www.medworm.com/rss/comments.php?id=5510631 Thu, 15 Dec 2011 05:00:00 +0100 5510631 http://www.medworm.com/index.php?rid=5510630&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1309%3Frss%3D1 To maintain tissue homeostasis, some organs are able to replace dying cells with additional proliferation of surviving cells. Such proliferation can be localized (e.g., a regeneration blastema) or diffuse (compensatory growth). The relationship between such growth and the growth that occurs during development has not been characterized in detail. Drosophila melanogaster larval imaginal discs can recover from extensive damage, producing normally sized adult organs. Here we describe a system using genetic mosaics to screen for recessive mutations that impair compensatory growth. By generating clones of cells that carry a temperature-sensitive cell-lethal mutation, we conditionally ablate patches of tissue in the imaginal disc and assess the ability of the surviving sister clones to replace t... Genetics journals http://www.medworm.com/rss/comments.php?id=5510630 Thu, 15 Dec 2011 05:00:00 +0100 5510630 http://www.medworm.com/index.php?rid=5510629&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1297%3Frss%3D1 The PHR (Pam/Highwire/RPM-1) proteins are evolutionarily conserved ubiquitin ligases that regulate axon guidance and synapse formation in Caenorhabditis elegans, Drosophila, zebrafish, and mice. In C. elegans, RPM-1 (Regulator of Presynaptic Morphology-1) functions in synapse formation, axon guidance, axon termination, and postsynaptic GLR-1 trafficking. Acting as an E3 ubiquitin ligase, RPM-1 negatively regulates a MAP kinase pathway that includes: dlk-1, mkk-4, and the p38 MAPK, pmk-3. Here we provide evidence that ppm-1, a serine/threonine phosphatase homologous to human PP2Cα(PPM1A) and PP2Cβ(PPM1B) acts as a second negative regulatory mechanism to control the dlk-1 pathway. We show that ppm-1 functions through its phosphatase activity in a parallel genetic pathway with glo-... Genetics journals http://www.medworm.com/rss/comments.php?id=5510629 Thu, 15 Dec 2011 05:00:00 +0100 5510629 http://www.medworm.com/index.php?rid=5510628&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1281%3Frss%3D1 In this study, the O7 gene was cloned by map-based cloning and confirmed by transgenic functional complementation and RNAi. The o7-ref allele has a 12-bp in-frame deletion. The four-amino-acid deletion caused low accumulation of o7 protein in vivo. The O7 gene encodes an acyl-activating enzyme with high similarity to AAE3. The opaque phenotype of the o7 mutant was produced by the reduction of protein body size and number caused by a decrease in the α-zeins concentrations. Analysis of amino acids and metabolites suggested that the O7 gene might affect amino acid biosynthesis by affecting α-ketoglutaric acid and oxaloacetic acid. Transgenic rice seeds containing RNAi constructs targeting the rice ortholog of maize O7 also produced lower amounts of seed proteins and displayed an o... Genetics journals http://www.medworm.com/rss/comments.php?id=5510628 Thu, 15 Dec 2011 05:00:00 +0100 5510628 http://www.medworm.com/index.php?rid=5510627&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1271%3Frss%3D1 We report here the isolation of o7 with a combination of map-based cloning and transposon tagging. We first identified an o7 candidate gene by map-based cloning. The putative o7-ref allele has a 12-bp in-frame deletion of codons 350–353 in a 528-codon-long acyl-CoA synthetase-like gene (ACS). We then confirmed this candidate gene by generating another mutant allele from a transposon-tagging experiment using the Activator/Dissociation (Ac/Ds) system in a W22 background. The second allele, isolated from ~1 million gametes, presented a 2-kb Ds insertion that resembles the single Ds component of double-Ds, McClintock’s original Dissociation element, at codon 496 of the ACS gene. PBs exhibited striking membrane invaginations in the o7-ref allele and a severe number reduction in the ... Genetics journals http://www.medworm.com/rss/comments.php?id=5510627 Thu, 15 Dec 2011 05:00:00 +0100 5510627 http://www.medworm.com/index.php?rid=5510626&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1261%3Frss%3D1 In aerobic organisms, protection from oxidative damage involves the combined action of enzymatic and nonproteinaceous cellular factors that collectively remove harmful reactive oxygen species. One class of nonproteinaceous antioxidants includes small molecule complexes of manganese (Mn) that can scavenge superoxide anion radicals and provide a backup for superoxide dismutase enzymes. Such Mn antioxidants have been identified in diverse organisms; however, nothing regarding their physiology in the context of cellular adaptation to stress was known. Using a molecular genetic approach in Bakers’ yeast, Saccharomyces cerevisiae, we report that the Mn antioxidants can fall under control of the same pathways used for nutrient sensing and stress responses. Specifically, a serine/threonine P... Genetics journals http://www.medworm.com/rss/comments.php?id=5510626 Thu, 15 Dec 2011 05:00:00 +0100 5510626 http://www.medworm.com/index.php?rid=5510625&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1249%3Frss%3D1 Mutations at the APM1 and APM2 loci in the green alga Chlamydomonas reinhardtii confer resistance to phosphorothioamidate and dinitroaniline herbicides. Genetic interactions between apm1 and apm2 mutations suggest an interaction between the gene products. We identified the APM1 and APM2 genes using a map-based cloning strategy. Genomic DNA fragments containing only the DNJ1 gene encoding a type I Hsp40 protein rescue apm1 mutant phenotypes, conferring sensitivity to the herbicides and rescuing a temperature-sensitive growth defect. Lesions at five apm1 alleles include missense mutations and nucleotide insertions and deletions that result in altered proteins or very low levels of gene expression. The HSP70A gene, encoding a cytosolic Hsp70 protein known to interact with Hsp40 proteins, maps... Genetics journals http://www.medworm.com/rss/comments.php?id=5510625 Thu, 15 Dec 2011 05:00:00 +0100 5510625 http://www.medworm.com/index.php?rid=5510624&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1235%3Frss%3D1 RNA polymerase (pol) II establishes many protein–protein interactions with transcriptional regulators to coordinate different steps of transcription. Although some of these interactions have been well described, little is known about the existence of RNA pol II regions involved in contact with transcriptional regulators. We hypothesize that conserved regions on the surface of RNA pol II contact transcriptional regulators. We identified such an RNA pol II conserved region that includes the majority of the "foot" domain and identified interactions of this region with Mvp1, a protein required for sorting proteins to the vacuole, and Spo14, a phospholipase D. Deletion of MVP1 and SPO14 affects the transcription of their target genes and increases phosphorylation of Ser5 in the carboxy-te... Genetics journals http://www.medworm.com/rss/comments.php?id=5510624 Thu, 15 Dec 2011 05:00:00 +0100 5510624 http://www.medworm.com/index.php?rid=5510623&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1225%3Frss%3D1 One of the least understood aspects of homologous recombination is the process by which the ends of a double-strand break (DSB) search the entire genome for homologous templates that can be used to repair the break. We took advantage of the natural competition between the alternative donors HML and HMR employed during HO endonuclease-induced switching of the budding yeast MAT locus. The strong mating-type-dependent bias in the choice of the donors is enforced by the recombination enhancer (RE), which lies 17 kb proximal to HML. We investigated factors that improve the use of the disfavored donor. We show that the normal heterochromatic state of the donors does not impair donor usage, as donor choice is not affected by removing this epigenetic silencing. In contrast, increasing the length o... Genetics journals http://www.medworm.com/rss/comments.php?id=5510623 Thu, 15 Dec 2011 05:00:00 +0100 5510623 http://www.medworm.com/index.php?rid=5510622&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1211%3Frss%3D1 We have used a novel method to activate the DNA damage S-phase checkpoint response in Saccharomyces cerevisiae to slow lagging-strand DNA replication by exposing cells expressing a drug-sensitive DNA polymerase (L612M-DNA pol ) to the inhibitory drug phosphonoacetic acid (PAA). PAA-treated pol3-L612M cells arrest as large-budded cells with a single nucleus in the bud neck. This arrest requires all of the components of the S-phase DNA damage checkpoint: Mec1, Rad9, the DNA damage clamp Ddc1-Rad17-Mec3, and the Rad24-dependent clamp loader, but does not depend on Mrc1, which acts as the signaling adapter for the replication checkpoint. In addition to the above components, a fully functional mismatch repair system, including Exo1, is required to activate the S-phase damage checkpoint and for ... Genetics journals http://www.medworm.com/rss/comments.php?id=5510622 Thu, 15 Dec 2011 05:00:00 +0100 5510622 http://www.medworm.com/index.php?rid=5510621&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1203%3Frss%3D1 Finding the genes underlying complex traits is difficult. We show that new sequencing technology combined with traditional genetic techniques can efficiently identify genetic regions underlying a complex and quantitative behavioral trait. As a proof of concept we used phenotype-based introgression to backcross loci that control innate food preference in Drosophila simulans into the genomic background of D. sechellia, which expresses the opposite preference. We successfully mapped D. simulans introgression regions in a small mapping population (30 flies) with whole-genome resequencing using light coverage (~1x). We found six loci contributing to D. simulans food preference, one of which overlaps a previously discovered allele. This approach is applicable to many systems, does not rely on la... Genetics journals http://www.medworm.com/rss/comments.php?id=5510621 Thu, 15 Dec 2011 05:00:00 +0100 5510621 http://www.medworm.com/index.php?rid=5510620&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1177%3Frss%3D1 TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5510620 Thu, 15 Dec 2011 05:00:00 +0100 5510620 http://www.medworm.com/index.php?rid=5510619&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1145%3Frss%3D1 The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI si... Genetics journals http://www.medworm.com/rss/comments.php?id=5510619 Thu, 15 Dec 2011 05:00:00 +0100 5510619 http://www.medworm.com/index.php?rid=5510618&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1135%3Frss%3D1 Increasing the college graduation rates of underrepresented minority students in science disciplines is essential to attain a diverse workforce for the 21st century. The Research Internship and Science Education (RISE) program attempts to motivate and prepare students from the Atlanta Public School system, where underrepresented minority (URM) students comprise a majority of the population, for biomedical science careers by offering the opportunity to participate in an original research project. Students work in a research laboratory from the summer of their sophomore year until graduation, mentored by undergraduate and graduate students and postdoctoral fellows (postdocs). In addition, they receive instruction in college-level biology, scholastic assessment test (SAT) preparation classes,... Genetics journals http://www.medworm.com/rss/comments.php?id=5510618 Thu, 15 Dec 2011 05:00:00 +0100 5510618 http://www.medworm.com/index.php?rid=5510617&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1129%3Frss%3D1 To honor James F. Crow on the occasion of his 95th birthday, GENETICS has commissioned a series of Perspectives and Reviews. For GENETICS to publish the honorifics is fitting, as from their birth Crow and GENETICS have been paired. Crow was scheduled to be born in January 1916, the same month that the first issue of GENETICS was scheduled to appear, and in the many years that Crow has made major contributions to the conceptual foundations of modern genetics, GENETICS has chronicled his and other major advances in the field. The commissioned Perspectives and Reviews summarize and celebrate Professor Crow’s contributions as a research scientist, administrator, colleague, community supporter, international leader, teacher, and mentor. In science, Professor Crow was the international lea... Genetics journals http://www.medworm.com/rss/comments.php?id=5510617 Thu, 15 Dec 2011 05:00:00 +0100 5510617 http://www.medworm.com/index.php?rid=5510616&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2F1127%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5510616 Thu, 15 Dec 2011 05:00:00 +0100 5510616 http://www.medworm.com/index.php?rid=5510615&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F4%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5510615 Thu, 15 Dec 2011 05:00:00 +0100 5510615 http://www.medworm.com/index.php?rid=5415558&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1121%3Frss%3D1 We tested whether functionally important sites in bacterial, yeast, and animal promoters are more conserved than their neighbors. We found that substitutions are predominantly seen in less important sites and that those that occurred tended to have less impact on gene expression than possible alternatives. These results suggest that purifying selection operates on promoter sequences. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415558 Mon, 14 Nov 2011 05:00:00 +0100 5415558 http://www.medworm.com/index.php?rid=5415557&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1117%3Frss%3D1 Gene expression in Anopheles gambiae shows a deficiency of testis-expressed genes on the X chromosome associated with an excessive movement of retrogene duplication. We suggest that the degeneration of sex chromosomes in this monandrous species is likely the result of pressures from X inactivation, dosage compensation, and sexual antagonism. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415557 Mon, 14 Nov 2011 05:00:00 +0100 5415557 http://www.medworm.com/index.php?rid=5415556&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1103%3Frss%3D1 Allopolyploidy is an important process during plant evolution that results in the reunion of two divergent genomes into a common nucleus. Many of the immediate as well as longer-term genomic and epigenetic responses to polyploidy have become appreciated. To investigate the modifications of gene expression at the proteome level caused by allopolyploid formation, we conducted a comparative analysis of cotton seed proteomes from the allopolyploid Gossypium hirsutum (AD genome) and its model A-genome and D-genome diploid progenitors. An unexpectedly high level of divergence among the three proteomes was found, with about one-third of all protein forms being genome specific. Comparative analysis showed that there is a higher degree of proteomic similarity between the allopolyploid and its D-gen... Genetics journals http://www.medworm.com/rss/comments.php?id=5415556 Mon, 14 Nov 2011 05:00:00 +0100 5415556 http://www.medworm.com/index.php?rid=5415555&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1093%3Frss%3D1 There is increasing evidence that epigenetic marks such as DNA methylation contribute to phenotypic variation by regulating gene transcription, developmental plasticity, and interactions with the environment. However, relatively little is known about the relationship between the stability and distribution of DNA methylation within chromosomes and the ability to detect trait loci. Plant genomes have a distinct range of target sites and more extensive DNA methylation than animals. We analyzed the stability and distribution of epialleles within the complex genome of the oilseed crop plant Brassica napus. For methylation sensitive AFLP (MSAP) and retrotransposon (RT) epimarkers, we found a high degree of stability, with 90% of mapped markers retaining their allelic pattern in contrasting envir... Genetics journals http://www.medworm.com/rss/comments.php?id=5415555 Mon, 14 Nov 2011 05:00:00 +0100 5415555 http://www.medworm.com/index.php?rid=5415554&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1083%3Frss%3D1 In this study, we first examined whether male sterility is due solely to the single locus S24. An analysis of near-isogenic lines (NIL-F1) showed different phenotypes for S24 in different genetic backgrounds. The S24 heterozygote with the japonica genetic background showed male semisterility, but no sterility was found in heterozygotes with the indica background. This result indicates that S24 is regulated epistatically. A QTL analysis of a BC2F1 population revealed a novel sterility locus that interacts with S24 and is found on rice chromosome 2. The locus was named Epistatic Factor for S24 (EFS). Further genetic analyses revealed that S24 causes male sterility when in combination with the homozygous japonica EFS allele (efs-j). The results suggest that efs-j is a recessive sporophytic al... Genetics journals http://www.medworm.com/rss/comments.php?id=5415554 Mon, 14 Nov 2011 05:00:00 +0100 5415554 http://www.medworm.com/index.php?rid=5415553&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1069%3Frss%3D1 Mothers are often the most important determinant of traits expressed by their offspring. These "maternal effects" (MEs) are especially crucial in early development, but can also persist into adulthood. They have been shown to play a role in a diversity of evolutionary and ecological processes, especially when genetically based. Although the importance of MEs is becoming widely appreciated, we know little about their underlying genetic basis. We address the dearth of genetic data by providing a simple approach, using combined genotype information from parents and offspring, to identify "maternal genetic effects" (MGEs) contributing to natural variation in complex traits. Combined with experimental cross-fostering, our approach also allows for the separation of pre- and postnatal MGEs, provi... Genetics journals http://www.medworm.com/rss/comments.php?id=5415553 Mon, 14 Nov 2011 05:00:00 +0100 5415553 http://www.medworm.com/index.php?rid=5415552&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1061%3Frss%3D1 The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer’s diseas... Genetics journals http://www.medworm.com/rss/comments.php?id=5415552 Mon, 14 Nov 2011 05:00:00 +0100 5415552 http://www.medworm.com/index.php?rid=5415551&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1045%3Frss%3D1 A fundamental problem of asexual adaptation is that beneficial substitutions are not efficiently accumulated in large populations: Beneficial mutations often go extinct because they compete with one another in going to fixation. It has been argued that such clonal interference may have led to the evolution of sex and recombination in well-mixed populations. Here, we study clonal interference, and mechanisms of its mitigation, in an evolutionary model of spatially structured populations with uniform selection pressure. Clonal interference is much more prevalent with spatial structure than without, due to the slow wave-like spread of beneficial mutations through space. We find that the adaptation speed of asexuals saturates when the linear habitat size exceeds a characteristic interference l... Genetics journals http://www.medworm.com/rss/comments.php?id=5415551 Mon, 14 Nov 2011 05:00:00 +0100 5415551 http://www.medworm.com/index.php?rid=5415550&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1029%3Frss%3D1 We consider an asexual population under strong selection–weak mutation conditions evolving on rugged fitness landscapes with many local fitness peaks. Unlike the previous studies in which the initial fitness of the population is assumed to be high, here we start the adaptation process with a low fitness corresponding to a population in a stressful novel environment. For generic fitness distributions, using an analytic argument we find that the average number of steps to a local optimum varies logarithmically with the genotype sequence length and increases as the correlations among genotypic fitnesses increase. When the fitnesses are exponentially or uniformly distributed, using an evolution equation for the distribution of population fitness, we analytically calculate the fitness dis... Genetics journals http://www.medworm.com/rss/comments.php?id=5415550 Mon, 14 Nov 2011 05:00:00 +0100 5415550 http://www.medworm.com/index.php?rid=5415549&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1011%3Frss%3D1 Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation–selection balance conditions for X–autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosom... Genetics journals http://www.medworm.com/rss/comments.php?id=5415549 Mon, 14 Nov 2011 05:00:00 +0100 5415549 http://www.medworm.com/index.php?rid=5415548&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F1001%3Frss%3D1 Understanding the genetic basis of reproductive isolation between recently diverged species is a central problem in evolutionary genetics. Here, I present analyses of the genetic architecture underlying hybrid male sterility and segregation distortion between the Bogota and USA subspecies of Drosophila pseudoobscura. Previously, a single gene, Overdrive (Ovd), was shown to be necessary but not sufficient for both male sterility and segregation distortion in F1 hybrids between these subspecies, requiring several interacting partner loci for full manifestation of hybrid phenomena. I map these partner loci separately on the Bogota X chromosome and USA autosomes using a combination of different mapping strategies. I find that hybrid sterility involves a single hybrid incompatibility of at leas... Genetics journals http://www.medworm.com/rss/comments.php?id=5415548 Mon, 14 Nov 2011 05:00:00 +0100 5415548 http://www.medworm.com/index.php?rid=5415547&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F989%3Frss%3D1 In many biological scenarios, from the development of drug resistance in pathogens to the progression of healthy cells toward cancer, quantifying the selection acting on observed mutations is a central question. One difficulty in answering this question is the complexity of the background upon which mutations can arise, with multiple potential interactions between genetic loci. We here present a method for discerning selection from a population history that accounts for interference between mutations. Given sequences sampled from multiple time points in the history of a population, we infer selection at each locus by maximizing a likelihood function derived from a multilocus evolution model. We apply the method to the question of distinguishing between loci where new mutations are under po... Genetics journals http://www.medworm.com/rss/comments.php?id=5415547 Mon, 14 Nov 2011 05:00:00 +0100 5415547 http://www.medworm.com/index.php?rid=5415546&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F977%3Frss%3D1 We describe a general method for finding the distribution of genealogies: we allow migration between demes, splitting of demes [as in the isolation-with-migration (IM) model], and recombination between linked loci. These processes are described by a set of linear recursions for the generating function of branch lengths. Under the infinite-sites model, the probability of any configuration of mutations can be found by differentiating this generating function. Such calculations are feasible for small numbers of sampled genomes: as an example, we show how the generating function can be derived explicitly for three genes under the two-deme IM model. This derivation is done automatically, using Mathematica. Given data from a large number of unlinked and nonrecombining blocks of sequence, these r... Genetics journals http://www.medworm.com/rss/comments.php?id=5415546 Mon, 14 Nov 2011 05:00:00 +0100 5415546 http://www.medworm.com/index.php?rid=5415545&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F967%3Frss%3D1 In this study, we investigate allelic variation at microRNA loci in the nematode Caenorhabditis briggsae, a close relative of C. elegans. Phylogeographic structure in C. briggsae partitions most strains from around the globe into a "temperate" or a "tropical" clade, with a few strains having divergent, geographically restricted genotypes. Remarkably, strains that follow this latitudinal dichotomy also differ in temperature-associated fitness. With this phylogeographic pattern in mind, we examined polymorphisms in 18 miRNAs in a global sample of C. briggsae isolates and tested whether newly isolated strains conform to this phylogeography. Surprisingly, nucleotide diversity is relatively high in this class of gene that generally experiences strong purifying selection. In particular, we find ... Genetics journals http://www.medworm.com/rss/comments.php?id=5415545 Mon, 14 Nov 2011 05:00:00 +0100 5415545 http://www.medworm.com/index.php?rid=5415544&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F951%3Frss%3D1 How genomic diversity within bacterial populations originates and is maintained in the presence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and tick vectors. To understand mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23 genomes representing major genomic groups in North America and Europe. Linkage analysis of >13,500 single-nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Although three times more frequent than point mutation, recombination is localized and weakly affects genome-wide linkage disequilibrium. We show by ... Genetics journals http://www.medworm.com/rss/comments.php?id=5415544 Mon, 14 Nov 2011 05:00:00 +0100 5415544 http://www.medworm.com/index.php?rid=5415543&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F939%3Frss%3D1 Adaptations are constructed through the sequential substitution of beneficial mutations by natural selection. However, the rarity of beneficial mutations has precluded efforts to describe even their most basic properties. Do beneficial mutations typically confer small or large fitness gains? Are their fitness effects environment specific, or are they broadly beneficial across a range of environments? To answer these questions, we used two subsets (n = 18 and n = 63) of a large library of mutants carrying antibiotic resistance mutations in the bacterium Pseudomonas fluorescens whose fitness, along with the antibiotic sensitive ancestor, was assayed across 95 novel environments differing in the carbon source available for growth. We explore patterns of genotype-by-environment (GxE) interacti... Genetics journals http://www.medworm.com/rss/comments.php?id=5415543 Mon, 14 Nov 2011 05:00:00 +0100 5415543 http://www.medworm.com/index.php?rid=5415542&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F923%3Frss%3D1 Deleterious mutations tend to be recessive. Several theories, notably those of Fisher (based on selection) and Wright (based on metabolism), have been put forward to explain this pattern. Despite a long-lasting debate, the matter remains unresolved. This debate has focused on the average dominance of mutations. However, we also know very little about the distribution of dominance coefficients among mutations, and about its variation across environments. In this article we present a new approach to predicting this distribution. Our approach is based on a phenotypic fitness landscape model. First, we show that under a very broad range of conditions (and environments), the average dominance of mutation of small effects should be approximately one-quarter as long as adaptation of organisms to ... Genetics journals http://www.medworm.com/rss/comments.php?id=5415542 Mon, 14 Nov 2011 05:00:00 +0100 5415542 http://www.medworm.com/index.php?rid=5415541&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F907%3Frss%3D1 Cytoplasmic polyadenylation element binding (CPEB) proteins bind mRNAs to regulate their localization and translation. While the first CPEBs discovered were germline specific, subsequent studies indicate that CPEBs also function in many somatic tissues including the nervous system. Drosophila has two CPEB family members. One of these, orb, plays a key role in the establishment of polarity axes in the developing egg and early embryo, but has no known somatic functions or expression outside of the germline. Here we characterize the other Drosophila CPEB, orb2. Unlike orb, orb2 mRNA and protein are found throughout development in many different somatic tissues. While orb2 mRNA and protein of maternal origin are distributed uniformly in early embryos, this pattern changes as development procee... Genetics journals http://www.medworm.com/rss/comments.php?id=5415541 Mon, 14 Nov 2011 05:00:00 +0100 5415541 http://www.medworm.com/index.php?rid=5415540&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F899%3Frss%3D1 Gradients of acetylcholine can stimulate growth cone turning when applied to neurons grown in culture, and it has been suggested that acetylcholine could act as a guidance cue. However, the role acetylcholine plays in directing axon migrations in vivo is not clear. Here, we show that acetylcholine positively regulates signaling pathways that mediate axon responses to guidance cues in Caenorhabditis elegans. Mutations that disrupt acetylcholine synthesis, transportation, and secretion affect circumferential axon guidance of the AVM neuron and in these mutants exogenously supplied acetylcholine improves AVM circumferential axon guidance. These effects are not observed for the circumferential guidance of the DD and VD motor neuron axons, which are neighbors of the AVM axon. Circumferential gu... Genetics journals http://www.medworm.com/rss/comments.php?id=5415540 Mon, 14 Nov 2011 05:00:00 +0100 5415540 http://www.medworm.com/index.php?rid=5415539&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F885%3Frss%3D1 The acquisition and maintenance of shape is critical for the normal function of most cells. Here we investigate the morphology of the pharyngeal glands of Caenorhabditis elegans. These unicellular glands have long cellular processes that extend discrete lengths through the pharyngeal musculature and terminate at ducts connected to the pharyngeal lumen. From a genetic screen we identified several mutants that affect pharyngeal gland morphology. The most severe such mutant is an allele of sma-1, which encodes a β-spectrin required for embryonic elongation, including elongation of the pharynx. In sma-1 mutants, gland projections form normally but become increasingly abnormal over time, acquiring additional branches, outgrowths, and swelling, suggestive of hypertrophy. Rather than acting ... Genetics journals http://www.medworm.com/rss/comments.php?id=5415539 Mon, 14 Nov 2011 05:00:00 +0100 5415539 http://www.medworm.com/index.php?rid=5415538&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F871%3Frss%3D1 The steroid hormone 20-hydroxyecdysone (20E) regulates gene transcription through the heterodimeric nuclear receptor composed of ecdysone receptor (EcR) and Ultraspiracle (USP). The EcR gene encodes three protein isoforms—A, B1, and B2—with variant N-terminal domains that mediate tissue and developmental stage-specific responses to 20E. Ariadne-1a is a conserved member of the RING finger family of ubiquitin ligases first identified in Drosophila melanogaster. Loss-of-function mutations at key cysteines in either of the two RING finger motifs, as well as general overexpression of this enzyme, cause lethality in pupae, which suggests a requirement in metamorphosis. Here, we show that Ariadne-1a binds specifically the isoform A of EcR and ubiquitylates it. Co-immunoprecipitation e... Genetics journals http://www.medworm.com/rss/comments.php?id=5415538 Mon, 14 Nov 2011 05:00:00 +0100 5415538 http://www.medworm.com/index.php?rid=5415537&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F861%3Frss%3D1 The Minute syndrome in Drosophila melanogaster is characterized by delayed development, poor fertility, and short slender bristles. Many Minute loci correspond to disruptions of genes for cytoplasmic ribosomal proteins, and therefore the phenotype has been attributed to alterations in translational processes. Although protein translation is crucial for all cells in an organism, it is unclear why Minute mutations cause effects in specific tissues. To determine whether the heart is sensitive to haplo-insufficiency of genes encoding ribosomal proteins, we measured heart function of Minute mutants using optical coherence tomography. We found that cardiomyopathy is associated with the Minute syndrome caused by haplo-insufficiency of genes encoding cytoplasmic ribosomal proteins. While mutations... Genetics journals http://www.medworm.com/rss/comments.php?id=5415537 Mon, 14 Nov 2011 05:00:00 +0100 5415537 http://www.medworm.com/index.php?rid=5415536&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F851%3Frss%3D1 Properly coordinated defense signaling networks are critical for the fitness of plants. One hub of the defense networks is centered on salicylic acid (SA), which plays a key role in activating disease resistance in plants. However, while a number of genes are known to affect SA-mediated defense, relatively little is known about how these gene interact genetically with each other. Here we exploited the unique defense-sensitized Arabidopsis mutant accelerated cell death (acd) 6-1 to dissect functional relationships among key components in the SA hub. We show that while enhanced disease susceptibility (eds) 1-2 and phytoalexin deficient (pad) 4-1 suppressed acd6-1–conferred small size, cell death, and defense phenotypes, a combination of these two mutations did not incur additive suppre... Genetics journals http://www.medworm.com/rss/comments.php?id=5415536 Mon, 14 Nov 2011 05:00:00 +0100 5415536 http://www.medworm.com/index.php?rid=5415535&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F837%3Frss%3D1 Regulation of transcription can be a complex process in which many cis- and trans-interactions determine the final pattern of expression. Among these interactions are trans-interactions mediated by the pairing of homologous chromosomes. These trans-effects are wide ranging, affecting gene regulation in many species and creating complex possibilities in gene regulation. Here we describe a novel case of trans-interaction between alleles of the Malic enzyme (Men) locus in Drosophila melanogaster that results in allele-specific, non-additive gene expression. Using both empirical biochemical and predictive bioinformatic approaches, we show that the regulatory elements of one allele are capable of interacting in trans with, and modifying the expression of, the second allele. Furthermore, we show... Genetics journals http://www.medworm.com/rss/comments.php?id=5415535 Mon, 14 Nov 2011 05:00:00 +0100 5415535 http://www.medworm.com/index.php?rid=5415534&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F825%3Frss%3D1 The yeast transcriptional activator Gal4 localizes to UASGAL sites even in the absence of galactose but cannot activate transcription due to an association with the Gal80 protein. By 4 min after galactose addition, Gal4-activated gene transcription ensues. It is well established that this rapid induction arises through a galactose-triggered association between the Gal80 and Gal3 proteins that decreases the association of Gal80 and Gal4. How this happens mechanistically remains unclear. Strikingly different hypotheses prevail concerning the possible roles of nucleocytoplasmic distribution and trafficking of Gal3 and Gal80 and where in the cell the initial Gal3–Gal80 association occurs. Here we tested two conflicting hypotheses by evaluating the subcellular distribution and dynamics of... Genetics journals http://www.medworm.com/rss/comments.php?id=5415534 Mon, 14 Nov 2011 05:00:00 +0100 5415534 http://www.medworm.com/index.php?rid=5415533&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F809%3Frss%3D1 It is well known that the Dpp signal transducer Mad is activated by phosphorylation at its carboxy-terminus. The role of phosphorylation on other regions of Mad is not as well understood. Here we report that the phosphorylation of Mad in the linker region by the Wg antagonist Zw3 (homolog of vertebrate Gsk3-β) regulates the development of sensory organs in the anterior–dorsal quadrant of the wing. Proneural expression of Mad-RNA interference (RNAi) or a Mad transgene with its Zw3/Gsk3-β phosphorylation sites mutated (MGM) generated wings with ectopic sensilla and chemosensory bristle duplications. Studies with pMad-Gsk (an antibody specific to Zw3/Gsk3-β-phosphorylated Mad) in larval wing disks revealed that this phosphorylation event is Wg dependent (via an unconventi... Genetics journals http://www.medworm.com/rss/comments.php?id=5415533 Mon, 14 Nov 2011 05:00:00 +0100 5415533 http://www.medworm.com/index.php?rid=5415532&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F795%3Frss%3D1 In this study the genetic model organism, A. nidulans, has been used to investigate the regulation and molecular functions of the matA mating type gene in a homothallic system. Our data demonstrate that complex regulatory mechanisms underlie functional matA expression during self-fertilization and sexual reproduction in A. nidulans. matA expression is suppressed in vegetative hyphae and is progressively derepressed during the sexual cycle. Elevated levels of matA transcript are required for differentiation of fruiting bodies, karyogamy, meiosis, and efficient formation of meiotic progeny. matA expression is driven from both initiator (Inr) and novel promoter elements that are tightly developmentally regulated by position-dependent and position-independent mechanisms. Deletion of an upstrea... Genetics journals http://www.medworm.com/rss/comments.php?id=5415532 Mon, 14 Nov 2011 05:00:00 +0100 5415532 http://www.medworm.com/index.php?rid=5415531&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F779%3Frss%3D1 In many organisms, homolog pairing and synapsis at meiotic prophase depend on interactions between chromosomes and the nuclear membrane. Male Drosophila lack synapsis, but nonetheless, their chromosomes closely associate with the nuclear periphery at prophase I. To explore the functional significance of this association, we characterize mutations in nuclear blebber (nbl), a gene required for both spermatocyte nuclear shape and meiotic chromosome transmission. We demonstrate that nbl corresponds to dtopors, the Drosophila homolog of the mammalian dual ubiquitin/small ubiquitin-related modifier (SUMO) ligase Topors. We show that mutations in dtopors cause abnormalities in lamin localizations, centriole separation, and prophase I chromatin condensation and also cause anaphase I bridges that l... Genetics journals http://www.medworm.com/rss/comments.php?id=5415531 Mon, 14 Nov 2011 05:00:00 +0100 5415531 http://www.medworm.com/index.php?rid=5415530&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F767%3Frss%3D1 We report two genomic approaches for more rapidly determining the identity of the affected genes in Caenorhabditis elegans mutants. First, we report our use of restriction site-associated DNA (RAD) polymorphism markers for rapidly mapping mutations after chemical mutagenesis and mutant isolation. Second, we describe our use of genomic interval pull-down sequencing (GIPS) to selectively capture and sequence megabase-sized portions of a mutant genome. Together, these two methods provide a rapid and cost-effective approach for positional cloning of C. elegans mutant loci, and are also applicable to other genetic model systems. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415530 Mon, 14 Nov 2011 05:00:00 +0100 5415530 http://www.medworm.com/index.php?rid=5415529&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F737%3Frss%3D1 This article summarizes what is known about the molecular mechanisms controlling spore assembly with particular attention to how constitutive cellular functions are modified to create novel behaviors during this developmental process. Key regulatory points on the sporulation pathway are also discussed as well as the possible role of sporulation in the natural ecology of S. cerevisiae. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415529 Mon, 14 Nov 2011 05:00:00 +0100 5415529 http://www.medworm.com/index.php?rid=5415528&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F705%3Frss%3D1 Here we review recent advances in understanding the regulation of mRNA synthesis in Saccharomyces cerevisiae. Many fundamental gene regulatory mechanisms have been conserved in all eukaryotes, and budding yeast has been at the forefront in the discovery and dissection of these conserved mechanisms. Topics covered include upstream activation sequence and promoter structure, transcription factor classification, and examples of regulated transcription factor activity. We also examine advances in understanding the RNA polymerase II transcription machinery, conserved coactivator complexes, transcription activation domains, and the cooperation of these factors in gene regulatory mechanisms. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415528 Mon, 14 Nov 2011 05:00:00 +0100 5415528 http://www.medworm.com/index.php?rid=5415527&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F695%3Frss%3D1 In this essay, we revisit the status of yeast as a model system for biology. We first summarize important contributions of yeast to eukaryotic biology that we anticipated in 1988 in our first article on the subject. We then describe transformative developments that we did not anticipate, most of which followed the publication of the complete genomic sequence of Saccharomyces cerevisiae in 1996. In the intervening 23 years it appears to us that yeast has graduated from a position as the premier model for eukaryotic cell biology to become the pioneer organism that has facilitated the establishment of the entirely new fields of study called "functional genomics" and "systems biology." These new fields look beyond the functions of individual genes and proteins, focusing on how these interact a... Genetics journals http://www.medworm.com/rss/comments.php?id=5415527 Mon, 14 Nov 2011 05:00:00 +0100 5415527 http://www.medworm.com/index.php?rid=5415526&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F685%3Frss%3D1 We describe how a small number of single-base-pair substitutions can generate hotspots de novo and dramatically alter their distribution in the genome. This model also shows how equilibrium rate kinetics could maintain the presence of hotspots over evolutionary timescales, without strong selective pressures invoked previously, and explains why hotspots localize preferentially to intergenic regions and introns. The model is robust enough to account for all hotspots of humans and chimpanzees repositioned since their divergence from the latest common ancestor. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415526 Mon, 14 Nov 2011 05:00:00 +0100 5415526 http://www.medworm.com/index.php?rid=5415525&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2F683%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415525 Mon, 14 Nov 2011 05:00:00 +0100 5415525 http://www.medworm.com/index.php?rid=5415524&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F3%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5415524 Mon, 14 Nov 2011 05:00:00 +0100 5415524 http://www.medworm.com/index.php?rid=5320105&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F507%3Frss%3D1 Desiccation tolerance, the ability to survive nearly total dehydration, is a rare strategy for survival and reproduction observed in all taxa. However, the mechanism and regulation of this phenomenon are poorly understood. Correlations between desiccation tolerance and potential effectors have been reported in many species, but their physiological significance has not been established in vivo. Although the budding yeast Saccharomyces cerevisiae exhibits extreme desiccation tolerance, its usefulness has been hampered by an inability to reduce tolerance more than a few fold by physiological or genetic perturbations. Here we report that fewer than one in a million yeast cells from low-density logarithmic cultures survive desiccation, while 20–40% of cells from saturated cultures survive... Genetics journals http://www.medworm.com/rss/comments.php?id=5320105 Wed, 12 Oct 2011 04:00:00 +0100 5320105 http://www.medworm.com/index.php?rid=5309474&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F681%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5309474 Wed, 12 Oct 2011 04:00:00 +0100 5309474 http://www.medworm.com/index.php?rid=5309473&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F675%3Frss%3D1 Despite the prominent and worldwide use of Bacillus thuringiensis (Bt) insecticidal toxins in agriculture, knowledge of the mechanism by which they kill pests remains incomplete. Here we report genetic mapping of a membrane transporter (ABCC2) to a locus controlling Bt Cry1Ac toxin resistance in two lepidopterans, implying that this protein plays a critical role in Bt function. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5309473 Wed, 12 Oct 2011 04:00:00 +0100 5309473 http://www.medworm.com/index.php?rid=5309472&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F665%3Frss%3D1 Thyroid hormone has pleiotropic effects on cochlear development, and genomic variation influences the severity of associated hearing deficits. DW/J-Pou1f1dw/dw mutant mice lack pituitary thyrotropin, which causes severe thyroid hormone deficiency and profound hearing impairment. To assess the genetic complexity of protective effects on hypothyroidism-induced hearing impairment, an F1 intercross was generated between DW/J-Pou1f1dw/+ carriers and an inbred strain with excellent hearing derived from Mus castaneus, CAST/EiJ. Approximately 24% of the (DW/J x CAST/EiJ) Pou1f1dw/dw F2 progeny had normal hearing. A genome scan revealed a locus on chromosome 2, named modifier of dw hearing, or Mdwh, that rescues hearing despite persistent hypothyroidism. This chromosomal region contains the modifie... Genetics journals http://www.medworm.com/rss/comments.php?id=5309472 Wed, 12 Oct 2011 04:00:00 +0100 5309472 http://www.medworm.com/index.php?rid=5309471&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F655%3Frss%3D1 The constraint of a rotating earth has led to the evolution of a circadian clock that drives anticipation of future environmental changes. During this daily rotation, the circadian clock of Arabidopsis thaliana (Arabidopsis) intersects with the diurnal environment to orchestrate virtually all transcriptional processes of the plant cell, presumably by detecting, interpreting, and anticipating the environmental alternations of light and temperature. To comparatively assess differential inputs toward phenotypic and physiological responses on a circadian parameter, we surveyed clock periodicity in a recombinant inbred population modified to allow for robust periodicity measurements after entrainment to respective photic vs. thermal cues, termed zeitgebers. Lines previously thermally entrained ... Genetics journals http://www.medworm.com/rss/comments.php?id=5309471 Wed, 12 Oct 2011 04:00:00 +0100 5309471 http://www.medworm.com/index.php?rid=5309470&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F645%3Frss%3D1 We consider recombinant inbred lines obtained by crossing two given homozygous parents and then applying multiple generations of self-crossings or full-sib matings. The chromosomal content of any such line forms a mosaic of blocks, each alternatively inherited identically by descent from one of the parents. Quantifying the statistical properties of such mosaic genomes has remained an open challenge for many years. Here, we solve this problem by taking a continuous chromosome picture and assuming crossovers to be noninterfering. Using a continuous-time random walk framework and Markov chain theory, we determine the statistical properties of these identical-by-descent blocks. We find that successive block lengths are only very slightly correlated. Furthermore, the blocks on the ends of chrom... Genetics journals http://www.medworm.com/rss/comments.php?id=5309470 Wed, 12 Oct 2011 04:00:00 +0100 5309470 http://www.medworm.com/index.php?rid=5309469&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F633%3Frss%3D1 Effective population size (Ne) is an important genetic parameter because of its relationship to loss of genetic variation, increases in inbreeding, accumulation of mutations, and effectiveness of selection. Like most other genetic approaches that estimate contemporary Ne, the method based on linkage disequilibrium (LD) assumes a closed population and (in the most common applications) randomly recombining loci. We used analytical and numerical methods to evaluate the absolute and relative consequences of two potential violations of the closed-population assumption: (1) mixture LD caused by occurrence of more than one gene pool, which would downwardly bias $${\widehat{\hbox{ N }}}_{\hbox{ e }}$$, and (2) reductions in drift LD (and hence upward bias in $${\widehat{\hbox{ N }}}_{\hbox{ e }}$$... Genetics journals http://www.medworm.com/rss/comments.php?id=5309469 Wed, 12 Oct 2011 04:00:00 +0100 5309469 http://www.medworm.com/index.php?rid=5309468&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F621%3Frss%3D1 While it is well understood that the pace of evolution depends on the interplay between natural selection, random genetic drift, mutation, and gene flow, it is not always easy to disentangle the relative roles of these factors with data from natural populations. One popular approach to infer whether the observed degree of population differentiation has been influenced by local adaptation is the comparison of neutral marker gene differentiation (as reflected in FST) and quantitative trait divergence (as reflected in QST). However, this method may lead to compromised statistical power, because FST and QST are summary statistics which neglect information on specific pairs of populations, and because current multivariate tests of neutrality involve an averaging procedure over the traits. Furth... Genetics journals http://www.medworm.com/rss/comments.php?id=5309468 Wed, 12 Oct 2011 04:00:00 +0100 5309468 http://www.medworm.com/index.php?rid=5309467&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F607%3Frss%3D1 Meiotic recombination is a fundamental cellular mechanism in sexually reproducing organisms and its different forms, crossing over and gene conversion both play an important role in shaping genetic variation in populations. Here, we describe a coalescent-based full-likelihood Markov chain Monte Carlo (MCMC) method for jointly estimating the crossing-over, gene-conversion, and mean tract length parameters from population genomic data under a Bayesian framework. Although computationally more expensive than methods that use approximate likelihoods, the relative efficiency of our method is expected to be optimal in theory. Furthermore, it is also possible to obtain a posterior sample of genealogies for the data using this method. We first check the performance of the new method on simulated da... Genetics journals http://www.medworm.com/rss/comments.php?id=5309467 Wed, 12 Oct 2011 04:00:00 +0100 5309467 http://www.medworm.com/index.php?rid=5309466&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F595%3Frss%3D1 We live in an age in which our ability to collect large amounts of genome-wide genetic variation data offers the promise of providing the key to the understanding and treatment of genetic diseases. Over the next few years this effort will be spearheaded by so-called next-generation sequencing technologies, which provide vast amounts of short-read sequence data at relatively low cost. This technology is often used to detect unknown variation in regions that have been linked with a given disease or phenotype. However, error rates are significant, leading to some nontrivial issues when it comes to interpreting the data. In this article, we present a method with which to address questions of widespread interest: calling variants and estimating the population mutation rate. We show performance ... Genetics journals http://www.medworm.com/rss/comments.php?id=5309466 Wed, 12 Oct 2011 04:00:00 +0100 5309466 http://www.medworm.com/index.php?rid=5309465&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F579%3Frss%3D1 Simulation studies have demonstrated that a variety of patterns in worldwide genetic variation are compatible with the trends predicted by a serial founder model, in which populations expand outward from an initial source via a process in which new populations contain only subsets of the genetic diversity present in their parental populations. Here, we provide analytical results for key quantities under the serial founder model, deriving distributions of coalescence times for pairs of lineages sampled either from the same population or from different populations. We use these distributions to obtain expectations for coalescence times and for homozygosity and heterozygosity values. A predicted approximate linear decline in expected heterozygosity with increasing distance from the source pop... Genetics journals http://www.medworm.com/rss/comments.php?id=5309465 Wed, 12 Oct 2011 04:00:00 +0100 5309465 http://www.medworm.com/index.php?rid=5309464&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F561%3Frss%3D1 A new approach to assigning individuals to populations using genetic data is described. Most existing methods work by maximizing Hardy–Weinberg and linkage equilibrium within populations, neither of which will apply for many demographic histories. By including a demographic model, within a likelihood framework based on coalescent theory, we can jointly study demographic history and population assignment. Genealogies and population assignments are sampled from a posterior distribution using a general isolation-with-migration model for multiple populations. A measure of partition distance between assignments facilitates not only the summary of a posterior sample of assignments, but also the estimation of the posterior density for the demographic history. It is shown that joint estimate... Genetics journals http://www.medworm.com/rss/comments.php?id=5309464 Wed, 12 Oct 2011 04:00:00 +0100 5309464 http://www.medworm.com/index.php?rid=5309463&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F549%3Frss%3D1 In the nematode Caenorhabditis elegans, temperature-sensitive mutants of emb-1 arrest as one-cell embryos in metaphase of meiosis I in a manner that is indistinguishable from embryos that have been depleted of known subunits of the anaphase-promoting complex or cyclosome (APC/C). Here we show that the emb-1 phenotype is enhanced in double mutant combinations with known APC/C subunits and suppressed in double mutant combinations with known APC/C suppressors. In addition to its meiotic function, emb-1 is required for mitotic proliferation of the germline. These studies reveal that emb-1 encodes K10D2.4, a homolog of the small, recently discovered APC/C subunit, APC16. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5309463 Wed, 12 Oct 2011 04:00:00 +0100 5309463 http://www.medworm.com/index.php?rid=5309462&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F533%3Frss%3D1 In Saccharomyces cerevisiae, replication stress induced by hydroxyurea (HU) and methyl methanesulfonate (MMS) activates DNA integrity checkpoints; in checkpoint-defective yeast strains, HU treatment also induces morphological aberrations. We find that the sphingolipid pathway gene ISC1, the product of which catalyzes the generation of bioactive ceramides from complex sphingolipids, plays a novel role in determining cellular morphology following HU/MMS treatment. HU-treated isc1 cells display morphological aberrations, cell-wall defects, and defects in actin depolymerization. Swe1, a morphogenesis checkpoint regulator, and the cell cycle regulator Cdk1 play key roles in these morphological defects of isc1 cells. A genetic approach reveals that ISC1 interacts with other checkpoint proteins t... Genetics journals http://www.medworm.com/rss/comments.php?id=5309462 Wed, 12 Oct 2011 04:00:00 +0100 5309462 http://www.medworm.com/index.php?rid=5309461&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F521%3Frss%3D1 Hydrogen sulfide (H2S), an endogenously produced small molecule, protects animals from various stresses. Recent studies demonstrate that animals exposed to H2S are long lived, resistant to hypoxia, and resistant to ischemia–reperfusion injury. We performed a forward genetic screen to gain insights into the molecular mechanisms Caenorhabditis elegans uses to appropriately respond to H2S. At least two distinct pathways appear to be important for this response, including the H2S-oxidation pathway and the hydrogen cyanide (HCN)-assimilation pathway. The H2S-oxidation pathway requires two distinct enzymes important for the oxidation of H2S: the sulfide:quinone reductase sqrd-1 and the dioxygenase ethe-1. The HCN-assimilation pathway requires the cysteine synthase homologs cysl-1 and cysl-... Genetics journals http://www.medworm.com/rss/comments.php?id=5309461 Wed, 12 Oct 2011 04:00:00 +0100 5309461 http://www.medworm.com/index.php?rid=5309460&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F507%3Frss%3D1 Desiccation tolerance, the ability to survive nearly total dehydration, is a rare strategy for survival and reproduction observed in all taxa. However, the mechanism and regulation of this phenomenon are poorly understood. Correlations between desiccation tolerance and potential effectors have been reported in many species, but their physiological significance has not been established in vivo. Although the budding yeast Saccharomyces cerevisiae exhibits extreme desiccation tolerance, its usefulness has been hampered by an inability to reduce tolerance more than a few fold by physiological or genetic perturbations. Here we report that fewer than one in a million yeast cells from low-density logarithmic cultures survive desiccation, while 20–40% of cells from saturated cultures survive... Genetics journals http://www.medworm.com/rss/comments.php?id=5309460 Wed, 12 Oct 2011 04:00:00 +0100 5309460 http://www.medworm.com/index.php?rid=5309459&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F495%3Frss%3D1 Influenza viruses impose a constant threat to vertebrates susceptible to this family of viruses. We have developed a new tool to study virus–host interactions that play key roles in viral replication and to help identify novel anti-influenza drug targets. Via the UAS/Gal4 system we ectopically expressed the influenza virus M2 gene in Drosophila melanogaster and generated dose-sensitive phenotypes in the eye and wing. We have confirmed that the M2 proton channel is properly targeted to cell membranes in Drosophila tissues and functions as a proton channel by altering intracellular pH. As part of the efficacy for potential anti-influenza drug screens, we have also demonstrated that the anti-influenza drug amantadine, which targets the M2 proton channel, suppressed the UAS-M2 mutant phe... Genetics journals http://www.medworm.com/rss/comments.php?id=5309459 Wed, 12 Oct 2011 04:00:00 +0100 5309459 http://www.medworm.com/index.php?rid=5309458&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F479%3Frss%3D1 In Saccharomyces cerevisiae, the TEA transcription factor Tec1 controls several developmental programs in response to nutrients and pheromones. Tec1 is targeted by the pheromone-responsive Fus3/Kss1 mitogen-activated protein kinase (MAPK) cascade, which destabilizes the transcription factor to ensure efficient mating of sexual partner cells. The regulation of Tec1 by signaling pathways that control cell division and development in response to nutrients, however, is not known. Here, we show that Tec1 protein stability is under control of the nutrient-sensitive target of rapamycin complex 1 (TORC1) signaling pathway via the Tip41-Tap42-Sit4 branch. We further show that degradation of Tec1 upon inhibition of TORC1 by rapamycin does not involve polyubiquitylation and appears to be proteasome i... Genetics journals http://www.medworm.com/rss/comments.php?id=5309458 Wed, 12 Oct 2011 04:00:00 +0100 5309458 http://www.medworm.com/index.php?rid=5309457&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F469%3Frss%3D1 The 5'-UTR serves as the loading dock for ribosomes during translation initiation and is the key site for translation regulation. Many genes in the yeast Saccharomyces cerevisiae contain poly(A) tracts in their 5'-UTRs. We studied these pre-AUG poly(A) tracts in a set of 3274 recently identified 5'-UTRs in the yeast to characterize their effect on in vivo protein abundance, ribosomal density, and protein synthesis rate in the yeast. The protein abundance and the protein synthesis rate increase with the length of the poly(A), but exhibit a dramatic decrease when the poly(A) length is ≥12. The ribosomal density also reaches the lowest level when the poly(A) length is ≥12. This supports the hypothesis that a pre-AUG poly(A) tract can bind to translation initiation factors to enhance tra... Genetics journals http://www.medworm.com/rss/comments.php?id=5309457 Wed, 12 Oct 2011 04:00:00 +0100 5309457 http://www.medworm.com/index.php?rid=5309456&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F455%3Frss%3D1 Metazoan genomes encode an abundant collection of mRNA-like, long noncoding (lnc)RNAs. Although lncRNAs greatly expand the transcriptional repertoire, we have a limited understanding of how these RNAs contribute to developmental regulation. Here, we investigate the function of the Drosophila lncRNA called yellow-achaete intergenic RNA (yar). Comparative sequence analyses show that the yar gene is conserved in Drosophila species representing 40–60 million years of evolution, with one of the conserved sequence motifs encompassing the yar promoter. Further, the timing of yar expression in Drosophila virilis parallels that in D. melanogaster, suggesting that transcriptional regulation of yar is conserved. The function of yar was defined by generating null alleles. Flies lacking yar RNAs ... Genetics journals http://www.medworm.com/rss/comments.php?id=5309456 Wed, 12 Oct 2011 04:00:00 +0100 5309456 http://www.medworm.com/index.php?rid=5309455&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F441%3Frss%3D1 In mammals, X-chromosome inactivation (XCI) equalizes X-linked gene expression between XY males and XX females and is controlled by a specialized region known as the X-inactivation center (Xic). The Xic harbors two chromatin interaction domains, one centered around the noncoding Xist gene and the other around the antisense Tsix counterpart. Previous work demonstrated the existence of a chromatin transitional zone between the two domains. Here, we investigate the region and discover a conserved element, RS14, that presents a strong binding site for Ctcf protein. RS14 possesses an insulatory function suggestive of a boundary element and is crucial for cell differentiation and growth. Knocking out RS14 results in compromised Xist induction and aberrant XCI in female cells. These data demonstr... Genetics journals http://www.medworm.com/rss/comments.php?id=5309455 Wed, 12 Oct 2011 04:00:00 +0100 5309455 http://www.medworm.com/index.php?rid=5309454&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F423%3Frss%3D1 The budding yeast Saccharomyces cerevisiae has proven to be a rich source of information about the mechanisms and regulation of homologous recombination during meiosis. A common technique for studying this process involves microdissecting the four products (ascospores) of a single meiosis and analyzing the configuration of genetic markers in the spores that are viable. Although this type of analysis is powerful, it can be laborious and time-consuming to characterize the large numbers of meioses needed to generate statistically robust data sets. Moreover, the reliance on viable (euploid) spores has the potential to introduce selection bias, especially when analyzing mutants with elevated frequencies of meiotic chromosome missegregation. To overcome these limitations, we developed a versatil... Genetics journals http://www.medworm.com/rss/comments.php?id=5309454 Wed, 12 Oct 2011 04:00:00 +0100 5309454 http://www.medworm.com/index.php?rid=5309453&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F411%3Frss%3D1 Four different SYP proteins (SYP-1, SYP-2, SYP-3, and SYP-4) have been proposed to form the central region of the synaptonemal complex (SC) thereby bridging the axes of paired meiotic chromosomes in Caenorhabditis elegans. Their interdependent localization suggests that they may interact within the SC. Our studies reveal for the first time how these SYP proteins are organized in the central region of the SC. Yeast two-hybrid and co-immunoprecipitation studies show that SYP-1 is the only SYP protein that is capable of homotypic interactions, and is able to interact with both SYP-2 and SYP-3 directly, whereas SYP-2 and SYP-3 do not seem to interact with each other. Specifically, the coiled-coil domain of SYP-1 is required both for its homotypic interactions and its interaction with the C-ter... Genetics journals http://www.medworm.com/rss/comments.php?id=5309453 Wed, 12 Oct 2011 04:00:00 +0100 5309453 http://www.medworm.com/index.php?rid=5309452&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2F405%3Frss%3D1 The structure of the meiosis-specific synaptonemal complex, which is perhaps the central visible characteristic of meiotic prophase, has been a matter of intense interest for decades. Although a general picture of the interactions between the transverse filament proteins that create this structure has emerged from studies in a variety of organisms, a recent analysis of synaptonemal complex structure in Caenorhabditis elegans by Schild-Prüfert et al. (2011) has provided the clearest picture of the structure of the architecture of a synaptonemal complex to date. Although the transverse filaments of the worm synaptonemal complex are assembled differently then those observed in yeast, mammalian, and Drosophila synaptonemal complexes, a comparison of the four assemblies shows that achievin... Genetics journals http://www.medworm.com/rss/comments.php?id=5309452 Wed, 12 Oct 2011 04:00:00 +0100 5309452 http://www.medworm.com/index.php?rid=5309451&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F2%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5309451 Wed, 12 Oct 2011 04:00:00 +0100 5309451 http://www.medworm.com/index.php?rid=5202140&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F397%3Frss%3D1 We investigate the generation and decay of interspecific disequilibrium (ID) between organelle and symbiont genomes as a function of the rate of horizontal transmission. We show that rare horizontal transmission greatly diminishes the covariance between organelle and symbiont genomes. This result has two important implications. First, a low level of ID does not indicate low levels of vertical transmission. Second, even with low levels of horizontal transmission, the additive effects of host and symbiont loci will determine the response to selection, while epistatic effects will not be selectable. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5202140 Fri, 09 Sep 2011 04:00:00 +0100 5202140 http://www.medworm.com/index.php?rid=5202139&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F391%3Frss%3D1 At present C31 is the only phage integrase system available for directionally regulated site-specific DNA integration in the Drosophila genome. Here we report that mycobacteriophage Bxb1 integrase also mediates targeted DNA integration in Drosophila with high specificity and efficiency. By alternately using Bxb1 and C31, we were able to carry out multiple rounds of successive and targeted DNA integrations in our genomic engineering founder lines for the purpose of generating complex knock-in alleles. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5202139 Fri, 09 Sep 2011 04:00:00 +0100 5202139 http://www.medworm.com/index.php?rid=5202138&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F375%3Frss%3D1 Developmental mechanisms that enable perception of and response to the environment may enhance fitness. Ecophysiological traits typically vary depending on local conditions and contribute to resource acquisition and allocation, yet correlations may limit adaptive trait expression. Notably, photosynthesis and stomatal conductance vary diurnally, and the circadian clock, which is an internal estimate of time that anticipates diurnal light/dark cycles, may synchronize physiological behaviors with environmental conditions. Using recombinant inbred lines of Brassica rapa, we examined the quantitative-genetic architecture of ecophysiological and phenological traits and tested their association with the circadian clock. We also investigated how trait expression differed across treatments that sim... Genetics journals http://www.medworm.com/rss/comments.php?id=5202138 Fri, 09 Sep 2011 04:00:00 +0100 5202138 http://www.medworm.com/index.php?rid=5202137&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F357%3Frss%3D1 The external genitalia are some of the most rapidly evolving morphological structures in insects. The posterior lobe of the male genital arch shows striking differences in both size and shape among closely related species of the Drosophila melanogaster species subgroup. Here, we dissect the genetic basis of posterior lobe morphology between D. mauritiana and D. sechellia, two island endemic species that last shared a common ancestor ~300,000 years ago. We test a large collection of genome-wide homozygous D. mauritiana genetic introgressions, which collectively cover ~50% of the genome, for their morphological effects when placed in a D. sechellia genetic background. We find several introgressions that have large effects on posterior lobe morphology and that posterior lobe size and posterio... Genetics journals http://www.medworm.com/rss/comments.php?id=5202137 Fri, 09 Sep 2011 04:00:00 +0100 5202137 http://www.medworm.com/index.php?rid=5202136&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F341%3Frss%3D1 Aging is an important feature of animal biology characterized by progressive, degenerative changes in somatic and reproductive tissues. The rate of age-related degeneration is genetically controlled, since genes that influence lifespan have been identified. However, little is known about genes that affect reproductive aging or aging of specific somatic tissues. To identify genes that are important for controlling these degenerative changes, we used chemical mutagenesis to perform forward genetic screens in Caenorhabditis elegans. By conducting a screen focused on somatic aging, we identified mutant hermaphrodites that displayed extended periods of pharyngeal pumping, body movement, or survival. One of these mutations is a novel allele of the age-1 gene. age-1 encodes a phosphatidylinositol... Genetics journals http://www.medworm.com/rss/comments.php?id=5202136 Fri, 09 Sep 2011 04:00:00 +0100 5202136 http://www.medworm.com/index.php?rid=5202135&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F329%3Frss%3D1 In recent years, genome-wide association studies (GWAS) have uncovered a large number of susceptibility variants. Nevertheless, GWAS findings provide only tentative evidence of association, and replication studies are required to establish their validity. Due to this uncertainty, researchers often focus on top-ranking SNPs, instead of considering strict significance thresholds to guide replication efforts. The number of SNPs for replication is often determined ad hoc. We show how the rank-based approach can be used for sample size allocation in GWAS as well as for deciding on a number of SNPs for replication. The basis of this approach is the "ranking probability": chances that at least j true associations will rank among top u SNPs, when SNPs are sorted by P-value. By employing simple but... Genetics journals http://www.medworm.com/rss/comments.php?id=5202135 Fri, 09 Sep 2011 04:00:00 +0100 5202135 http://www.medworm.com/index.php?rid=5202134&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F317%3Frss%3D1 We describe a phasing algorithm (ChromoPhase) that utilizes this characteristic of finite populations to phase large sections of a chromosome. In addition to phasing, our method imputes missing genotypes in individuals genotyped at lower marker density when more densely genotyped relatives are available. ChromoPhase uses a pedigree to collect an individual’s (the proband) surrogate parents and offspring and uses genotypic similarity to identify its genomic surrogates. The algorithm then cycles through the relatives and genomic surrogates one at a time to find shared chromosome segments. Once a segment has been identified, any missing information in the proband is filled in with information from the relative. We tested ChromoPhase in a simulated population consisting of 400 individual... Genetics journals http://www.medworm.com/rss/comments.php?id=5202134 Fri, 09 Sep 2011 04:00:00 +0100 5202134 http://www.medworm.com/index.php?rid=5202133&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F305%3Frss%3D1 In genetic studies, many interesting traits, including growth curves and skeletal shape, have temporal or spatial structure. They are better treated as curves or function-valued traits. Identification of genetic loci contributing to such traits is facilitated by specialized methods that explicitly address the function-valued nature of the data. Current methods for mapping function-valued traits are mostly likelihood-based, requiring specification of the distribution and error structure. However, such specification is difficult or impractical in many scenarios. We propose a general functional regression approach based on estimating equations that is robust to misspecification of the covariance structure. Estimation is based on a two-step least-squares algorithm, which is fast and applicable... Genetics journals http://www.medworm.com/rss/comments.php?id=5202133 Fri, 09 Sep 2011 04:00:00 +0100 5202133 http://www.medworm.com/index.php?rid=5202132&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F289%3Frss%3D1 Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Finding the genes involved in these incompatibilities provides insight into the mechanisms of speciation. With recently diverged subspecies, house mice provide a powerful system for understanding the genetics of reproductive isolation early in the speciation process. Although previous studies have yielded important clues about the genetics of hybrid male sterility in house mice, they have been restricted to F1 sterility or incompatibilities involving the X chromosome. To provide a more complete characterization of this key reproductive barrier, we conducted an F2 intercross between wild-derived inbred strains from two subspecies of house mice, Mus musculus musculus and Mus musculus dom... Genetics journals http://www.medworm.com/rss/comments.php?id=5202132 Fri, 09 Sep 2011 04:00:00 +0100 5202132 http://www.medworm.com/index.php?rid=5202131&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F267%3Frss%3D1 Disruption of interactions among ensembles of epistatic loci has been shown to contribute to reproductive isolation among various animal and plant species. Under the Bateson–Dobzhansky–Muller model, such interspecific incompatibility arises as a by-product of genetic divergence in each species, and the Orr–Turelli model indicates that the number of loci involved in incompatible interactions may "snowball" over time. We address the combined effect of multiple incompatibility loci on the rate of introgression at neutral marker loci across the genome. Our analysis extends previous work by accommodating sex specificity: differences between the sexes in the expression of incompatibility, in rates of crossing over between neutral markers and incompatibility loci, and in transmi... Genetics journals http://www.medworm.com/rss/comments.php?id=5202131 Fri, 09 Sep 2011 04:00:00 +0100 5202131 http://www.medworm.com/index.php?rid=5202130&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F251%3Frss%3D1 Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the ... Genetics journals http://www.medworm.com/rss/comments.php?id=5202130 Fri, 09 Sep 2011 04:00:00 +0100 5202130 http://www.medworm.com/index.php?rid=5202129&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F237%3Frss%3D1 Inbreeding depression, which refers to reduced fitness among offspring of related parents, has traditionally been studied using pedigrees. In practice, pedigree information is difficult to obtain, potentially unreliable, and rarely assessed for inbreeding arising from common ancestors who lived more than a few generations ago. Recently, there has been excitement about using SNP data to estimate inbreeding (F) arising from distant common ancestors in apparently "outbred" populations. Statistical power to detect inbreeding depression using SNP data depends on the actual variation in inbreeding in a population, the accuracy of detecting that with marker data, the effect size, and the sample size. No one has yet investigated what variation in F is expected in SNP data as a function of populati... Genetics journals http://www.medworm.com/rss/comments.php?id=5202129 Fri, 09 Sep 2011 04:00:00 +0100 5202129 http://www.medworm.com/index.php?rid=5202128&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F227%3Frss%3D1 Random genetic drift shifts clines in space, alters their width, and distorts their shape. Such random fluctuations complicate inferences from cline width and position. Notably, the effect of genetic drift on the expected shape of the cline is opposite to the naive (but quite common) misinterpretation of classic results on the expected cline. While random drift on average broadens the overall cline in expected allele frequency, it narrows the width of any particular cline. The opposing effects arise because locally, drift drives alleles to fixation—but fluctuations in position widen the expected cline. The effect of genetic drift can be predicted from standardized variance in allele frequencies, averaged across the habitat: <F>. A cline maintained by spatially varying selection... Genetics journals http://www.medworm.com/rss/comments.php?id=5202128 Fri, 09 Sep 2011 04:00:00 +0100 5202128 http://www.medworm.com/index.php?rid=5202127&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F213%3Frss%3D1 A central problem in population genetics is to detect and analyze positive natural selection by which beneficial mutations are driven to fixation. The hitchhiking effect of a rapidly spreading beneficial mutation, which results in local removal of standing genetic variation, allows such an analysis using DNA sequence polymorphism. However, the current mathematical theory that predicts the pattern of genetic hitchhiking relies on the assumption that a beneficial mutation increases to a high frequency in a single random-mating population, which is certainly violated in reality. Individuals in natural populations are distributed over a geographic space. The spread of a beneficial allele can be delayed by limited migration of individuals over the space and its hitchhiking effect can also be af... Genetics journals http://www.medworm.com/rss/comments.php?id=5202127 Fri, 09 Sep 2011 04:00:00 +0100 5202127 http://www.medworm.com/index.php?rid=5202126&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F195%3Frss%3D1 The male-specific Fruitless proteins (FruM) act to establish the potential for male courtship behavior in Drosophila melanogaster and are expressed in small groups of neurons throughout the nervous system. We screened ~1000 GAL4 lines, using assays for general courtship, male–male interactions, and male fertility to determine the phenotypes resulting from the GAL4-driven inhibition of FruM expression in subsets of these neurons. A battery of secondary assays showed that the phenotypic classes of GAL4 lines could be divided into subgroups on the basis of additional neurobiological and behavioral criteria. For example, in some lines, restoration of FruM expression in cholinergic neurons restores fertility or reduces male–male courtship. Persistent chains of males courting each ot... Genetics journals http://www.medworm.com/rss/comments.php?id=5202126 Fri, 09 Sep 2011 04:00:00 +0100 5202126 http://www.medworm.com/index.php?rid=5202125&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F177%3Frss%3D1 The CLAVATA1 (CLV1), CLV2, and CORYNE (CRN) receptors in Arabidopsis thaliana maintain cell proliferation in shoot apical meristems by restricting expression of the transcription factor WUSCHEL (WUS). Previously characterized receptor mutants generate extra fruit and floral organs that are proposed to arise from enlarged floral meristems (FMs). We identified new alleles in clv1, clv2, and crn and found that most mutants produce only extra fruit organs and generate FMs of similar dimensions as wild type. Characterization of gynoecium development in receptor mutants revealed increased cell proliferation and ectopic fruit organ initiation after FM termination. These regions of increased cell division also display expanded expression of the cell proliferation-promoting transcription factor SHO... Genetics journals http://www.medworm.com/rss/comments.php?id=5202125 Fri, 09 Sep 2011 04:00:00 +0100 5202125 http://www.medworm.com/index.php?rid=5202124&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F165%3Frss%3D1 Heterotrimeric (αβ) G proteins are crucial components of eukaryotic signal transduction pathways. G-protein-coupled receptors (GPCRs) act as guanine nucleotide exchange factors (GEFs) for Gα subunits. Recently, facilitated GDP/GTP exchange by non-GPCR GEFs, such as RIC8, has emerged as an important mechanism for Gα regulation in animals. RIC8 is present in animals and filamentous fungi, such as the model eukaryote Neurospora crassa, but is absent from the genomes of baker’s yeast and plants. In Neurospora, deletion of ric8 leads to profound defects in growth and asexual and sexual development, similar to those observed for a mutant lacking the Gα genes gna-1 and gna-3. In addition, constitutively activated alleles of gna-1 and gna-3 rescue many defects of... Genetics journals http://www.medworm.com/rss/comments.php?id=5202124 Fri, 09 Sep 2011 04:00:00 +0100 5202124 http://www.medworm.com/index.php?rid=5202123&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F153%3Frss%3D1 The processes that generate cellular morphology are not well understood. To investigate this problem, we use Drosophila melanogaster tracheal terminal cells, which undergo two distinct morphogenetic processes: subcellular branching morphogenesis and subcellular apical lumen formation. Here we show these processes are regulated by components of the PAR-polarity complex. This complex, composed of the proteins Par-6, Bazooka (Par-3), aPKC, and Cdc42, is best known for roles in asymmetric cell division and apical/basal polarity. We find Par-6, Bazooka, and aPKC, as well as known interactions between them, are required for subcellular branch initiation, but not for branch outgrowth. By analysis of single and double mutants, and isolation of two novel alleles of Par-6, one of which specifically ... Genetics journals http://www.medworm.com/rss/comments.php?id=5202123 Fri, 09 Sep 2011 04:00:00 +0100 5202123 http://www.medworm.com/index.php?rid=5202122&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F137%3Frss%3D1 Rho-family GTPases play regulatory roles in many fundamental cellular processes. Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migration, muscle arm extension, phagocytosis, and neurotransmission by activating either Rac or Rho GTPase subfamilies. Multiple differentially expressed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains. The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit Gαq and is required for normal rates of locomotion; however, mechanisms of UNC-73 and Rho pathway regulation of locomotion are not clear. To better define UNC-73 function in the regulation of motility we used cell-specific and inducible promoters to examine the temporal and spatial requirements of UNC-73 Rh... Genetics journals http://www.medworm.com/rss/comments.php?id=5202122 Fri, 09 Sep 2011 04:00:00 +0100 5202122 http://www.medworm.com/index.php?rid=5202121&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F123%3Frss%3D1 Microtubules are dynamic structures that must elongate, disassemble, and be cleaved into smaller pieces for proper neuronal development and function. The AAA ATPase Spastin severs microtubules along their lengths and is thought to regulate the balance between long, stable filaments and shorter fragments that seed extension or are transported. In both Drosophila and humans, loss of Spastin function results in reduction of synaptic connections and disabling motor defects. To gain insight into how spastin is regulated, we screened the Drosophila melanogaster genome for deletions that modify a spastin overexpression phenotype, eye size reduction. One suppressor region deleted p21-activated kinase 3 (pak3), which encodes a member of the Pak family of actin-regulatory enzymes, but whose in vivo ... Genetics journals http://www.medworm.com/rss/comments.php?id=5202121 Fri, 09 Sep 2011 04:00:00 +0100 5202121 http://www.medworm.com/index.php?rid=5202120&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F109%3Frss%3D1 Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on embryonic day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross F1 progeny of AKR and PWD mouse strains and quantified the allele-specific expression and the degree of parent-of-origin allelic imbalance. We confirmed the imprinting status of 23 known imprinted genes in the placenta and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a well-replicated design using an or... Genetics journals http://www.medworm.com/rss/comments.php?id=5202120 Fri, 09 Sep 2011 04:00:00 +0100 5202120 http://www.medworm.com/index.php?rid=5202119&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F97%3Frss%3D1 Regulation of alternative mRNA processing by ELAV (embryonic lethal abnormal visual system)/Hu proteins is mediated by binding to AU-rich elements of low complexity. Since such sequences diverge very rapidly during evolution, it has not been clear if ELAV regulation is maintained over extended phylogenetic distances. The transcription factor Erect wing (Ewg) is a major target of ELAV in Drosophila melanogaster and coordinates metabolic gene expression with regulation of synaptic plasticity. Here, we demonstrate evolutionary conservation of ELAV regulation of ewg despite massive degeneration of its binding site and of associated elements in the regulated intronic 3'-end processing site in distantly related Drosophila virilis. In this species, the RNA-binding part of ELAV protein is identica... Genetics journals http://www.medworm.com/rss/comments.php?id=5202119 Fri, 09 Sep 2011 04:00:00 +0100 5202119 http://www.medworm.com/index.php?rid=5202118&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F83%3Frss%3D1 In this study, we show that BRU1 also plays roles in gene regulation in euchromatic regions. bru1 mutations caused sporadic ectopic expression of genes, including those that encode master regulators of developmental programs such as stem cell maintenance and embryogenesis. bru1 mutants exhibited adventitious organogenesis, probably due to the misexpression of such developmental regulators. The key regulatory genes misregulated in bru1 alleles were often targets of PcG SET-domain proteins, although the overlap between the bru1-misregulated and PcG SET-domain-regulated genes was limited at a genome-wide level. Surprisingly, a considerable fraction of the genes activated in bru1 were located in several subchromosomal regions ranging from 174 to 944 kb in size. Our results suggest that BRU1 ha... Genetics journals http://www.medworm.com/rss/comments.php?id=5202118 Fri, 09 Sep 2011 04:00:00 +0100 5202118 http://www.medworm.com/index.php?rid=5202117&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F71%3Frss%3D1 We describe genetic studies indicating that while DSB-containing Sycp3–/– oocytes can be eliminated efficiently, those that survive have completed repair before the execution of an intact DNA damage checkpoint. We find that the requirement for DMC1 and TRIP13, proteins normally essential for recombination repair of meiotic DSBs, is substantially bypassed in Sycp3 and Sycp2 mutants. This bypass requires RAD54, a functionally conserved protein that promotes intersister recombination in yeast meiosis and mammalian mitotic cells. Immunocytological and genetic studies indicated that the bypass in Sycp3–/– Dmc1–/– oocytes was linked to increased DSB repair. These experiments lead us to hypothesize that axial elements mediate the activities of recombination pro... Genetics journals http://www.medworm.com/rss/comments.php?id=5202117 Fri, 09 Sep 2011 04:00:00 +0100 5202117 http://www.medworm.com/index.php?rid=5202116&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F55%3Frss%3D1 A large region of suppressed recombination surrounds the sex-determining locus of the self-fertile fungus Neurospora tetrasperma. This region encompasses nearly one-fifth of the N. tetrasperma genome and suppression of recombination is necessary for self-fertility. The similarity of the N. tetrasperma mating chromosome to plant and animal sex chromosomes and its recent origin (<5 MYA), combined with a long history of genetic and cytological research, make this fungus an ideal model for studying the evolutionary consequences of suppressed recombination. Here we compare genome sequences from two N. tetrasperma strains of opposite mating type to determine whether structural rearrangements are associated with the nonrecombining region and to examine the effect of suppressed recombination fo... Genetics journals http://www.medworm.com/rss/comments.php?id=5202116 Fri, 09 Sep 2011 04:00:00 +0100 5202116 http://www.medworm.com/index.php?rid=5202115&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F37%3Frss%3D1 Populations adapt physiologically using regulatory mechanisms and genetically by means of mutations that improve growth. During growth under selection, genetic adaptation can be rapid. In several genetic systems, the speed of adaptation has been attributed to cellular mechanisms that increase mutation rates in response to growth limitation. An alternative possibility is that growth limitation serves only as a selective agent but acts on small-effect mutations that are common under all growth conditions. The genetic systems that initially suggested stress-induced mutagenesis have been analyzed without regard for multistep adaptation and some include features that make such analysis difficult. To test the selection-only model, a simpler system is examined, whose behavior was originally attri... Genetics journals http://www.medworm.com/rss/comments.php?id=5202115 Fri, 09 Sep 2011 04:00:00 +0100 5202115 http://www.medworm.com/index.php?rid=5202114&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F23%3Frss%3D1 We report that hyper-TLD in uvrD cells is partly RecA dependent and cannot be attributed to accumulation of intermediates in mismatch repair or nucleotide-excision repair. These data imply that both its known role in opposing RecA and an additional as-yet-unknown function of UvrD promote TLD resistance. The hyper-TLD of ruvABC cells requires RecA but not RecQ or RecJ. The hyper-TLD of recB cells requires neither RecA nor RecQ, implying that neither recombination nor SOS induction causes hyper-TLD in recB cells, and RecQ is not the sole source of double-strand ends (DSEs) during TLD, as previously proposed; models are suggested. These results define pathways by which cells resist TLD and suggest strategies for combating TLD resistance during chemotherapies. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5202114 Fri, 09 Sep 2011 04:00:00 +0100 5202114 http://www.medworm.com/index.php?rid=5202113&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F11%3Frss%3D1 Hypoacetylated H4 is present at regional centromeres; however, its role in kinetochore function is poorly understood. We characterized H4 acetylation at point centromeres in Saccharomyces cerevisiae and determined the consequences of altered H4 acetylation on chromosome segregation. We observed low levels of tetra-acetylated and K16 acetylated histone H4 (H4K16Ac) at centromeres. Low levels of H4K16Ac were also observed at noncentromeric regions associated with Cse4p. Inhibition of histone deacetylases (HDAC) using nicotinamide (NAM) caused lethality in cse4 and hhf1-20 kinetochore mutants and increased centromeric H4K16Ac. Overexpression of Sas2-mediated H4K16 acetylation activity in wild-type cells led to increased rates of chromosome loss and synthetic dosage lethality in kinetochore mu... Genetics journals http://www.medworm.com/rss/comments.php?id=5202113 Fri, 09 Sep 2011 04:00:00 +0100 5202113 http://www.medworm.com/index.php?rid=5202112&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F3%3Frss%3D1 The discipline of classical genetics is founded on the hereditary behavior of the seven genes studied by Gregor Mendel. The advent of molecular techniques has unveiled much about the identity of these genes. To date, four genes have been sequenced: A (flower color), LE (stem length), I (cotyledon color), and R (seed shape). Two of the other three genes, GP (pod color) and FA (fasciation), are amenable to candidate gene approaches on the basis of their function, linkage relationships, and synteny between the pea and Medicago genomes. However, even the gene (locus) identity is not known for certain for the seventh character, the pod form, although it is probably V. While the nature of the mutations used by Mendel cannot be determined with certainty, on the basis of the varieties available in... Genetics journals http://www.medworm.com/rss/comments.php?id=5202112 Fri, 09 Sep 2011 04:00:00 +0100 5202112 http://www.medworm.com/index.php?rid=5202111&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2F1%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5202111 Fri, 09 Sep 2011 04:00:00 +0100 5202111 http://www.medworm.com/index.php?rid=5202110&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F189%2F1%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5202110 Fri, 09 Sep 2011 04:00:00 +0100 5202110 http://www.medworm.com/index.php?rid=5115570&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F188%2F4%2F1023%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5115570 Mon, 08 Aug 2011 23:00:00 +0100 5115570 http://www.medworm.com/index.php?rid=5115569&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F188%2F4%2F1019%3Frss%3D1 Quality protein maize combines a high-lysine trait with kernel hardness, for which a new, simpler genetic selection was designed. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=5115569 Mon, 08 Aug 2011 23:00:00 +0100 5115569