Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval.

abstract：:Recent genome-wide meta-analyses identified 157 loci associated with cross-sectional lipid traits. Here we tested whether these loci associate (singly and in trait-specific genetic risk scores [GRS]) with longitudinal changes in total cholesterol (TC) and triglyceride (TG) levels in a population-based prospective coho...

journal_title：PLoS genetics

authors： Varga TV,Sonestedt E,Shungin D,Koivula RW,Hallmans G,Escher SA,Barroso I,Nilsson P,Melander O,Orho-Melander M,Renström F,Franks PW

更新日期：2014-06-12 00:00:00

abstract：:Successful reproduction is critical to pass genes to the next generation. Seminal proteins contribute to important reproductive processes that lead to fertilization in species ranging from insects to mammals. In Drosophila, the male's accessory gland is a source of seminal fluid proteins that affect the reproductive o...

journal_title：PLoS genetics

authors： Ram KR,Wolfner MF

更新日期：2007-12-01 00:00:00

abstract：:[This corrects the article DOI: 10.1371/journal.pgen.1006940.]. ...

journal_title：PLoS genetics

authors： Nakanishi M,Nomura J,Ji X,Tamada K,Arai T,Takahashi E,Bućan M,Takumi T

更新日期：2017-10-03 00:00:00

abstract：:Bases within DNA are frequently damaged, producing obstacles to efficient and accurate DNA replication by replicative polymerases. Translesion synthesis (TLS) polymerases, via their ability to catalyze nucleotide additions to growing DNA chains across DNA lesions, promote replication of damaged DNA, thus preventing ch...

journal_title：PLoS genetics

authors： van Bostelen I,van Schendel R,Romeijn R,Tijsterman M

更新日期：2020-04-24 00:00:00

abstract：:Tripartite Motif (TRIM) ubiquitin ligases act in the innate immune response against viruses. One of the best characterized members of this family, TRIM5α, serves as a potent retroviral restriction factor with activity against HIV. Here, we characterize what are likely to be the youngest TRIM genes in the human genome....

journal_title：PLoS genetics

authors： Han K,Lou DI,Sawyer SL

更新日期：2011-12-01 00:00:00

abstract：:Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiate...

journal_title：PLoS genetics

authors： Skotnicka D,Smaldone GT,Petters T,Trampari E,Liang J,Kaever V,Malone JG,Singer M,Søgaard-Andersen L

更新日期：2016-05-23 00:00:00

abstract：:Entry into mitosis is triggered by activation of Cdk1 and inactivation of its counteracting phosphatase PP2A/B55. Greatwall kinase inactivates PP2A/B55 via its substrates Ensa and ARPP19. Both Greatwall and Ensa/ARPP19 are regulated by phosphorylation, but the dynamic regulation of Greatwall activity and the phosphata...

journal_title：PLoS genetics

authors： Hégarat N,Vesely C,Vinod PK,Ocasio C,Peter N,Gannon J,Oliver AW,Novák B,Hochegger H

更新日期：2014-01-01 00:00:00

abstract：:X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by mutations of the myotubularin gene, MTM1. Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., "MTMRs"). Biochemically, catalytically inacti...

journal_title：PLoS genetics

authors： Gupta VA,Hnia K,Smith LL,Gundry SR,McIntire JE,Shimazu J,Bass JR,Talbot EA,Amoasii L,Goldman NE,Laporte J,Beggs AH

更新日期：2013-06-01 00:00:00

abstract：:Wnt signaling provides a paradigm for cell-cell signals that regulate embryonic development and stem cell homeostasis and are inappropriately activated in cancers. The tumor suppressors APC and Axin form the core of the multiprotein destruction complex, which targets the Wnt-effector beta-catenin for phosphorylation, ...

journal_title：PLoS genetics

authors： Schaefer KN,Bonello TT,Zhang S,Williams CE,Roberts DM,McKay DJ,Peifer M

更新日期：2018-04-11 00:00:00

abstract：:Nephrolithiasis is a common nephrologic disorder with complex etiology. To identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases and 17,809 controls of Japanese origin. Here we found three novel loci for nephroli...

journal_title：PLoS genetics

authors： Urabe Y,Tanikawa C,Takahashi A,Okada Y,Morizono T,Tsunoda T,Kamatani N,Kohri K,Chayama K,Kubo M,Nakamura Y,Matsuda K

更新日期：2012-01-01 00:00:00

abstract：:A variety of human diseases arise from mutations that alter muscle contraction. Evolutionary conservation allows genetic studies in Drosophila melanogaster to be used to better understand these myopathies and suggest novel therapeutic strategies. Integrin-mediated adhesion is required to support muscle structure and f...

journal_title：PLoS genetics

authors： Pronovost SM,Beckerle MC,Kadrmas JL

更新日期：2013-03-01 00:00:00

abstract：:Invasion of epithelial cells by Salmonella enterica requires expression of genes located in the pathogenicity island I (SPI-1). The expression of SPI-1 genes is very tightly regulated and activated only under specific conditions. Most studies have focused on the regulatory pathways that induce SPI-1 expression. Here, ...

journal_title：PLoS genetics

authors： El Mouali Y,Gaviria-Cantin T,Sánchez-Romero MA,Gibert M,Westermann AJ,Vogel J,Balsalobre C

更新日期：2018-06-07 00:00:00

abstract：:The rate of germline mutation varies widely between species but little is known about the extent of variation in the germline mutation rate between individuals of the same species. Here we demonstrate that an allele that increases the rate of germline mutation can result in a distinctive signature in the genomic regio...

journal_title：PLoS genetics

authors： Seoighe C,Scally A

更新日期：2017-01-17 00:00:00

abstract：:The Structural Maintenance of Chromosome (SMC) complex, termed cohesin, is essential for sister chromatid cohesion. Cohesin is also important for chromosome condensation, DNA repair, and gene expression. Cohesin is comprised of Scc3, Mcd1, Smc1, and Smc3. Scc3 also binds Pds5 and Wpl1, cohesin-associated proteins that...

journal_title：PLoS genetics

authors： Orgil O,Matityahu A,Eng T,Guacci V,Koshland D,Onn I

更新日期：2015-03-06 00:00:00

abstract：:70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and acc...

journal_title：PLoS genetics

authors： Andersson R,Eisele-Bürger AM,Hanzén S,Vielfort K,Öling D,Eisele F,Johansson G,Gustafsson T,Kvint K,Nyström T

更新日期：2021-01-11 00:00:00

abstract：:Convergent phenotypic evolution is often caused by recurrent changes at particular nodes in the underlying gene regulatory networks (GRNs). The genes at such evolutionary 'hotspots' are thought to maximally affect the phenotype with minimal pleiotropic consequences. This has led to the suggestion that if a GRN is unde...

journal_title：PLoS genetics

authors： Kittelmann S,Buffry AD,Franke FA,Almudi I,Yoth M,Sabaris G,Couso JP,Nunes MDS,Frankel N,Gómez-Skarmeta JL,Pueyo-Marques J,Arif S,McGregor AP

更新日期：2018-05-03 00:00:00

abstract：:Differentiating cells interact with their extracellular environment over time. Chondrocytes embed themselves in a proteoglycan (PG)-rich matrix, then undergo a developmental transition, termed "maturation," when they express ihh to induce bone in the overlying tissue, the perichondrium. Here, we ask whether PGs regula...

journal_title：PLoS genetics

authors： Eames BF,Yan YL,Swartz ME,Levic DS,Knapik EW,Postlethwait JH,Kimmel CB

更新日期：2011-08-01 00:00:00

abstract：:Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electr...

journal_title：PLoS genetics

authors： Federowicz S,Kim D,Ebrahim A,Lerman J,Nagarajan H,Cho BK,Zengler K,Palsson B

更新日期：2014-04-03 00:00:00

abstract：:At least 25 inherited disorders in humans result from microsatellite repeat expansion. Dramatic variation in repeat instability occurs at different disease loci and between different tissues; however, cis-elements and trans-factors regulating the instability process remain undefined. Genomic fragments from the human s...

journal_title：PLoS genetics

authors： Libby RT,Hagerman KA,Pineda VV,Lau R,Cho DH,Baccam SL,Axford MM,Cleary JD,Moore JM,Sopher BL,Tapscott SJ,Filippova GN,Pearson CE,La Spada AR

更新日期：2008-11-01 00:00:00

abstract：:The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten...

journal_title：PLoS genetics

authors： Hallast P,Balaresque P,Bowden GR,Ballereau S,Jobling MA

更新日期：2013-01-01 00:00:00

abstract：:The metabolic capabilities and regulatory networks of bacteria have been optimized by evolution in response to selective pressures present in each species' native ecological niche. In a new environment, however, the same bacteria may grow poorly due to regulatory constraints or biochemical deficiencies. Adaptation to ...

journal_title：PLoS genetics

authors： Hottes AK,Freddolino PL,Khare A,Donnell ZN,Liu JC,Tavazoie S

更新日期：2013-01-01 00:00:00

abstract：:The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans (C. elegans). Glycine, in ...

journal_title：PLoS genetics

authors： Liu YJ,Janssens GE,McIntyre RL,Molenaars M,Kamble R,Gao AW,Jongejan A,Weeghel MV,MacInnes AW,Houtkooper RH

更新日期：2019-03-07 00:00:00

abstract：:Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebraf...

journal_title：PLoS genetics

authors： Weger BD,Weger M,Görling B,Schink A,Gobet C,Keime C,Poschet G,Jost B,Krone N,Hell R,Gachon F,Luy B,Dickmeis T

更新日期：2016-12-12 00:00:00

abstract：:Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tra...

journal_title：PLoS genetics

authors： Fox BA,Sanders KL,Rommereim LM,Guevara RB,Bzik DJ

更新日期：2016-07-22 00:00:00

abstract：:Mating-type switching is a complex mechanism that promotes sexual reproduction in Saccharomycotina. In the model species Saccharomyces cerevisiae, mating-type switching is initiated by the Ho endonuclease that performs a site-specific double-strand break (DSB) at MAT, repaired by homologous recombination (HR) using on...

journal_title：PLoS genetics

authors： Maroc L,Zhou-Li Y,Boisnard S,Fairhead C

更新日期：2020-10-15 00:00:00

abstract：:While there has been much recent focus on the ecological causes of adaptive diversification, we know less about the genetic nature of the trade-offs in resource use that create and maintain stable, diversified ecotypes. Here we show how a regulatory genetic change can contribute to sympatric diversification caused by ...

journal_title：PLoS genetics

authors： Spencer CC,Bertrand M,Travisano M,Doebeli M

更新日期：2007-01-19 00:00:00

abstract：:Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by maternal deficiency of the imprinted gene UBE3A. Individuals with AS suffer from intellectual disability, speech impairment, and motor dysfunction. Currently there is no cure for the disease. Here, we evaluated the phenotypic effect of activating...

journal_title：PLoS genetics

authors： Meng L,Person RE,Huang W,Zhu PJ,Costa-Mattioli M,Beaudet AL

更新日期：2013-01-01 00:00:00

abstract：:The female gametophyte of flowering plants, the embryo sac, develops within the diploid (sporophytic) tissue of the ovule. While embryo sac-expressed genes are known to be required at multiple stages of the fertilization process, the set of embryo sac-expressed genes has remained poorly defined. In particular, the set...

journal_title：PLoS genetics

authors： Jones-Rhoades MW,Borevitz JO,Preuss D

更新日期：2007-10-01 00:00:00

abstract：:Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs...

journal_title：PLoS genetics

authors： Mansour TA,Lucot K,Konopelski SE,Dickinson PJ,Sturges BK,Vernau KL,Choi S,Stern JA,Thomasy SM,Döring S,Verstraete FJM,Johnson EG,York D,Rebhun RB,Ho HH,Brown CT,Bannasch DL

更新日期：2018-12-06 00:00:00

abstract：:DNA methyltransferases are ubiquitous enzymes conserved in bacteria, plants and opisthokonta. These enzymes, which methylate cytosines, are involved in numerous biological processes, notably development. In mammals and higher plants, methylation patterns established and maintained by the cytosine DNA methyltransferase...

journal_title：PLoS genetics

authors： Grognet P,Timpano H,Carlier F,Aït-Benkhali J,Berteaux-Lecellier V,Debuchy R,Bidard F,Malagnac F

更新日期：2019-08-14 00:00:00