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Plos Genetics : the Transcriptomes of Two Heritable Cell Types Ill...

By: Gregory P. Copenhaver

Description : The differentiation of cells into distinct cell types, each of which is heritable for many generations, underlies many biological phenomena. White and opaque cells of the fungal pathogen Candida albicans are two such heritable cell types, each thought to be adapted to unique niches within their human host. To systematically investigate their differences, we performed strand-specific, massively-parallel sequencing of RNA from C. albicans white and opaque cel...

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Plos Genetics : Oaz-t, Volume 5

By: Gregory P. Copenhaver

Description : Polyamines are known to play important roles in the proliferation and differentiation of many types of cells. Although considerable amounts of polyamines are synthesized and stored in the testes, their roles remain unknown. Ornithine decarboxylase antizymes (OAZs) control the intracellular concentration of polyamines in a feedback manner. OAZ1 and OAZ2 are expressed ubiquitously, whereas OAZ-t/OAZ3 is expressed specifically in germline cells during spermiog...

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Plos Genetics : Senataxin Plays an Essential Role with Dna Damage ...

By: Peter J. McKinnon

Description : Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossingover in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Set...

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Plos Genetics : Whole-genome Sequencing of a Single Proband Togeth...

By: Gregory S. Barsh

Description : Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metac...

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Plos Genetics : the Ribosomal Protein Rpl22 Controls Ribosome Comp...

By: Gregory P. Copenhaver

Description : Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibil...

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Plos Genetics : Mapping of the Disease Locus and Identification of...

By: Gregory S. Barsh

Description : Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine ch...

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Plos Genetics : Bisphenol a Exposure in Utero Disrupts Early Oogen...

By: R. Scott Hawley

Description : Estrogen plays an essential role in the growth and maturation of the mammalian oocyte, and recent studies suggest that it also influences follicle formation in the neonatal ovary. In the course of studies designed to assess the effect of the estrogenic chemical bisphenol A (BPA) on mammalian oogenesis, we uncovered an estrogenic effect at an even earlier stage of oocyte development—at the onset of meiosis in the fetal ovary. Pregnant mice were treated with ...

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Plos Genetics : Dcaf26, an Adaptor Protein of Cul4-based E3, is Es...

By: Wendy A. Bickmore

Description : DNA methylation is involved in gene silencing and genome stability in organisms from fungi to mammals. Genetic studies in Neurospora crassa previously showed that the CUL4-DDB1 E3 ubiquitin ligase regulates DNA methylation via histone H3K9 trimethylation. However, the substrate-specific adaptors of this ligase that are involved in the process were not known. Here, we show that, among the 16 DDB1- and Cul4-associated factors (DCAFs) encoded in the N. crassa ...

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Plos Genetics : Role of Individual Subunits of the Neurospora Cras...

By: Xing Wang Deng

Description : The Cop9 signalosome (CSN) is an evolutionarily conserved multifunctional complex that controls ubiquitin-dependent protein degradation in eukaryotes. We found seven CSN subunits in Neurospora crassa in a previous study, but only one subunit, CSN-2, was functionally characterized. In this study, we created knockout mutants for the remaining individual CSN subunits in N. crassa. By phenotypic observation, we found that loss of CSN-1, CSN-2, CSN-4, CSN-5, CSN...

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Plos Genetics : Life on Arginine for Mycoplasma Hominis ; Clues fr...

By: Josep Casadesus

Description : Mycoplasma hominis is an opportunistic human mycoplasma. Two other pathogenic human species, M. genitalium and Ureaplasma parvum, reside within the same natural niche as M. hominis : the urogenital tract. These three species have overlapping, but distinct, pathogenic roles. They have minimal genomes and, thus, reduced metabolic capabilities characterized by distinct energy-generating pathways. Analysis of the M. hominis PG21 genome sequence revealed that it...

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Plos Genetics : Rumors of Its Disassembly Have Been Greatly Exagge...

By: Gregory P. Copenhaver
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Plos Genetics : Robust Prediction of Expression Differences Among ...

By: Greg Gibson

Description : Many genetic variants that are significantly correlated to gene expression changes across human individuals have been identified, but the ability of these variants to predict expression of unseen individuals has rarely been evaluated. Here, we devise an algorithm that, given training expression and genotype data for a set of individuals, predicts the expression of genes of unseen test individuals given only their genotype in the local genomic vicinity of th...

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Plos Genetics : Loss of the Dna Methyltransferase Met1 Induces H3K...

By: Anne C. Ferguson-smith

Description : Dimethylation of histone H3 lysine 9 (H3K9m2) and trimethylation of histone H3 lysine 27 (H3K27m3) are two hallmarks of transcriptional repression in many organisms. In Arabidopsis thaliana, H3K27m3 is targeted by Polycomb Group (PcG) proteins and is associated with silent protein-coding genes, while H3K9m2 is correlated with DNA methylation and is associated with transposons and repetitive sequences. Recently, ectopic genic DNA methylation in the CHG conte...

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Plos Genetics : Gene Expression Regulation by Upstream Open Readin...

By: Elizabeth M. C. Fisher

Description : Upstream open reading frames (uORFs) are major gene expression regulatory elements. In many eukaryotic mRNAs, one or more uORFs precede the initiation codon of the main coding region. Indeed, several studies have revealed that almost half of human transcripts present uORFs. Very interesting examples have shown that these uORFs can impact gene expression of the downstream main ORF by triggering mRNA decay or by regulating translation. Also, evidence from rec...

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Plos Genetics : Misregulation of Scm3P, Volume 7

By: Beth A. Sullivan

Description : The kinetochore (centromeric DNA and associated proteins) is a key determinant for high fidelity chromosome transmission. Evolutionarily conserved Scm3p is an essential component of centromeric chromatin and is required for assembly and function of kinetochores in humans, fission yeast, and budding yeast. Overexpression of HJURP, the mammalian homolog of budding yeast Scm3p, has been observed in lung and breast cancers and is associated with poor prognosis:...

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Plos Genetics : Stromal Liver Kinase B1 Stk11 Signaling Loss Induc...

By: Hamish S. Scott

Description : Germline mutations of the Liver Kinase b1 (LKB1/STK11) tumor suppressor gene have been linked to Peutz-Jeghers Syndrome (PJS), an autosomal-dominant, cancer-prone disorder in which patients develop neoplasms in several organs, including the oviduct, ovary, and cervix. We have conditionally deleted Lkb1 in Mu¨ llerian duct mesenchyme-derived cells of the female reproductive tract and observed expansion of the stromal compartment and hyperplasia and/or neopla...

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Plos Genetics : an Allele of an Ancestral Transcription Factor Dep...

By: Diarmaid Hughes

Description : Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription factor PmrA that requires the horizontally acquired pmrD gene product to promote gene expression. We determined that a single amino acid differenc...

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Plos Genetics : Fate of the H-ns–repressed Bgloperon in Evolution ...

By: Josep Casadesus

Description : In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS– repressed locus is the bgl (aryl-b,D-glucoside) operon of E. coli. This locus is ‘‘cryptic,’’ as no laboratory growth conditions are known to relieve repression of bgl by H-NS in E. coli K12. However, repression can be rel...

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Plos Genetics : Genome-wide Association Study Snps in the Human Ge...

By: Joshua M. Akey

Description : Genome-wide association studies (GWAS) have identified more than 2,000 trait-SNP associations, and the number continues to increase. GWAS have focused on traits with potential consequences for human fitness, including many immunological, metabolic, cardiovascular, and behavioral phenotypes. Given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci, a possibility which has y...

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Plos Genetics : Loss of Expression and Promoter Methylation of Sli...

By: Marshall S. Horwitz

Description : Serrated adenomas form a distinct subtype of colorectal pre-malignant lesions that may progress to malignancy along a different molecular pathway than the conventional adenoma-carcinoma pathway. Previous studies have hypothesised that BRAF mutation and promoter hypermethylation plays a role, but the evidence for this is not robust. We aimed to carry out a whole-genome loss of heterozygosity analysis, followed by targeted promoter methylation and expression ...

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