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Plos Genetics : a Fundamental Regulatory Mechanism Operating Throu...

By: Josep Casadesús

Description : DNA topology has fundamental control over the ability of transcription factors to access their target DNA sites at gene promoters. However, the influence of DNA topology on protein–DNA and protein–protein interactions is poorly understood. For example, relaxation of DNA supercoiling strongly induces the well-studied pathogenicity gene ssrA (also called spiR) in Salmonella enterica, but neither the mechanism nor the proteins involved are known. We have found...

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Plos Genetics : the Genetic Signatures of Noncoding Rnas, Volume 5

By: Jeannie T. Lee

Description : The majority of the genome in animals and plants is transcribed in a developmentally regulated manner to produce large numbers of non–protein-coding RNAs (ncRNAs), whose incidence increases with developmental complexity. There is growing evidence that these transcripts are functional, particularly in the regulation of epigenetic processes, leading to the suggestion that they compose a hitherto hidden layer of genomic programming in humans and other complex ...

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Plos Genetics : Let-7B, Volume 8

By: T. Rajendra Kumar

Description : Gene silencing mediated by either microRNAs (miRNAs) or Adenylate/uridylate-rich elements Mediated mRNA Degradation (AMD) is a powerful way to post-transcriptionally modulate gene expression. We and others have reported that the RNA– binding protein KSRP favors the biogenesis of select miRNAs (including let-7 family) and activates AMD promoting the decay of inherently labile mRNAs. Different layers of interplay between miRNA– and AMD–mediated gene silencing...

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Plos Genetics : Xpf and Not the Fanconi Anaemia Proteins or Rev3 A...

By: Raymond J. Monnat

Description : Organisms like Dictyostelium discoideum, often referred to as DNA damage ‘‘extremophiles’’, can survive exposure to extremely high doses of radiation and DNA crosslinking agents. These agents form highly toxic DNA crosslinks that cause extensive DNA damage. However, little is known about how Dictyostelium and the other ‘‘extremophiles’’ can tolerate and repair such large numbers of DNA crosslinks. Here we describe a comprehensive genetic analysis of crossli...

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Plos Genetics : the Transcription Factor Ultraspiracle Influences ...

By: Jürgen Gadau

Description : Behavior is among the most dynamic animal phenotypes, modulated by a variety of internal and external stimuli. Behavioral differences are associated with large-scale changes in gene expression, but little is known about how these changes are regulated. Here we show how a transcription factor (TF), ultraspiracle (usp: the insect homolog of the Retinoid X Receptor), working in complex transcriptional networks, can regulate behavioral plasticity and associated...

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Plos Genetics : the U-box E3 Ubiquitin Ligase Tud1 Functions with ...

By: Jianming Li

Description : Heterotrimeric G proteins are an important group of signaling molecules found in eukaryotes. They function with G-proteincoupled- receptors (GPCRs) to transduce various signals such as steroid hormones in animals. Nevertheless, their functions in plants are not well-defined. Previous studies suggested that the heterotrimeric G protein a subunit known as D1/RGA1 in rice is involved in a phytohormone gibberellin-mediated signaling pathway. Evidence also impli...

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Plos Genetics : Segregating Variation in the Polycomb Group Gene C...

By: Dmitri A. Petrov

Description : The phenotype produced by a given genotype can be strongly modulated by environmental conditions. Therefore, natural populations continuously adapt to environment heterogeneity to maintain optimal phenotypes. It generates a high genetic variation in environment-sensitive gene networks, which is thought to facilitate evolution. Here we analyze the chromatin regulator crm, identified as a candidate for adaptation of Drosophila melanogaster to northern latitud...

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Plos Genetics : Reductive Genome Evolution from the Mother of Rick...

By: Claire M. Fraser-liggett

Description : The Rickettsia genus is a group of obligate intracellular a-proteobacteria representing a paradigm of reductive evolution. Here, we investigate the evolutionary processes that shaped the genomes of the genus. The reconstruction of ancestral genomes indicates that their last common ancestor contained more genes, but already possessed most traits associated with cellular parasitism. The differences in gene repertoires across modern Rickettsia are mainly the r...

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Plos Genetics : is Mate Choice in Humans Mhc-dependent, Volume 4

By: Molly Przeworski

Description : In several species, including rodents and fish, it has been shown that the Major Histocompatibility Complex (MHC) influences mating preferences and, in some cases, that this may be mediated by preferences based on body odour. In humans, the picture has been less clear. Several studies have reported a tendency for humans to prefer MHC-dissimilar mates, a sexual selection that would favour the production of MHC-heterozygous offspring, who would be more resist...

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Plos Genetics : Evidence for Positive Selection on a Number of Mic...

By: Jianzhi Zhang

Description : MicroRNA (miRNA)–mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic d...

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Plos Genetics : Identifying Relationships Among Genomic Disease Re...

By: John D. Storey

Description : Translating a set of disease regions into insight about pathogenic mechanisms requires not only the ability to identify the key disease genes within them, but also the biological relationships among those key genes. Here we describe a statistical method, Gene Relationships Among Implicated Loci (GRAIL), that takes a list of disease regions and automatically assesses the degree of relatedness of implicated genes using 250,000 PubMed abstracts. We first evalu...

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Plos Genetics : Saccharomyces Cerevisiae Dna Ligase IV Supports Im...

By: Sue Jinks-robertson

Description : DNA ligase IV (Dnl4 in budding yeast) is a specialized ligase used in non-homologous end joining (NHEJ) of DNA doublestrand breaks (DSBs). Although point and truncation mutations arise in the human ligase IV syndrome, the roles of Dnl4 in DSB repair have mainly been examined using gene deletions. Here, Dnl4 catalytic point mutants were generated that were severely defective in auto-adenylation in vitro and NHEJ activity in vivo, despite being hyper-recruite...

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Plos Genetics : Genetic Crossovers Are Predicted Accurately by the...

By: Gil McVean

Description : Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the po...

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Plos Genetics : Evolution of a Novel Appendage Ground Plan in Wate...

By: David L. Stern

Description : Water striders, a group of semi-aquatic bugs adapted to life on the water surface, have evolved mid-legs (L2) that are long relative to their hind-legs (L3). This novel appendage ground plan is a derived feature among insects, where L2 function as oars and L3 as rudders. The Hox gene Ultrabithorax (Ubx) is known to increase appendage size in a variety of insects. Using gene expression and RNAi analysis, we discovered that Ubx is expressed in both L2 and L3,...

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Plos Genetics : Genic Intolerance to Functional Variation and the ...

By: Scott M. Williams

Description : A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progress has been made in scoring the functional impact of individual mutations, the characteristics of the genes in which those mutations are found remain largely unexplored. For example, genes known to carry few common functional variants in healthy individuals may be judged more likely to cause certain kinds of disease than genes kn...

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Plos Genetics : Variants Affecting Exon Skipping Contribute to Com...

By: Scott M. Williams

Description : DNA variants that affect alternative splicing and the relative quantities of different gene transcripts have been shown to be risk alleles for some Mendelian diseases. However, for complex traits characterized by a low odds ratio for any single contributing variant, very few studies have investigated the contribution of splicing variants. The overarching goal of this study is to discover and characterize the role that variants affecting alternative splicing...

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Plos Genetics : Cyclin E and Cdk2 Control Gld-1, the Mitosis, Volume 7

By: Sue Biggins

Description : Coordination of the cell cycle with developmental events is crucial for generation of tissues during development and their maintenance in adults. Defects in that coordination can shift the balance of cell fates with devastating clinical effects. Yet our understanding of the molecular mechanisms integrating core cell cycle regulators with developmental regulators remains in its infancy. This work focuses on the interplay between cell cycle and developmental ...

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Plos Genetics : Genome-wide Association Study of Coronary Heart Di...

By: Mark I. McCarthy

Description : Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD o...

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Plos Genetics : Inactivation of Pmel Alters Melanosome Shape but H...

By: Ian J. Jackson

Description : PMEL is an amyloidogenic protein that appears to be exclusively expressed in pigment cells and forms intralumenal fibrils within early stage melanosomes upon which eumelanins deposit in later stages. PMEL is well conserved among vertebrates, and allelic variants in several species are associated with reduced levels of eumelanin in epidermal tissues. However, in most of these cases it is not clear whether the allelic variants reflect gain-of-function or loss...

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Plos Genetics : Ctip Mutations Cause Seckel and Jawad Syndromes, V...

By: Veronica Van Heyningen

Description : Seckel syndrome is a recessively inherited dwarfism disorder characterized by microcephaly and a unique head profile. Genetically, it constitutes a heterogeneous condition, with several loci mapped (SCKL1-5) but only three disease genes identified : the ATR, CENPJ, and CEP152 genes that control cellular responses to DNA damage. We previously mapped a Seckel syndrome locus to chromosome 18p11.31-q11.2 (SCKL2). Here, we report two mutations in the CtIP (RBBP8...

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