31,627 results match your criteria GENETICS [Journal]


Multiple Pathways Act Together To Establish Asymmetry of the Ventral Nerve Cord in .

Genetics 2019 Feb 21. Epub 2019 Feb 21.

Simon Fraser University

The central nervous system of most animals is bilaterally symmetrical. Closer observation often reveals some functional or anatomical left-right asymmetries. In the nematode the most obvious asymmetry in the nervous system is found in the ventral nerve cord (VNC), where most axons are in the right axon tract. Read More

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http://dx.doi.org/10.1534/genetics.119.301999DOI Listing
February 2019

A Multivariate Genome-Wide Association Study of Wing Shape in .

Genetics 2019 Feb 21. Epub 2019 Feb 21.

Florida State University.

Due to the complexity of genotype-phenotype relationships, simultaneous analyses of genomic associations with multiple traits will be more powerful and informative than a series of univariate analyses. In most cases, however, studies of genotype-phenotype relationships have been analyzed only one trait at a time. Here, we report the results of a fully integrated multivariate genome-wide association analysis of the shape of the wing in the Drosophila Genetic Reference Panel. Read More

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http://dx.doi.org/10.1534/genetics.118.301342DOI Listing
February 2019

Publisher Correction: An evolutionary framework for measuring epigenomic information and estimating cell-type-specific fitness consequences.

Nat Genet 2019 Feb 20. Epub 2019 Feb 20.

Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

In the version of this article initially published, in the Methods section 'Statistics and data analysis', subsection 'Measuring entropy with INSIGHT', the equation for the maximized log likelihood incorrectly duplicated the equation for entropy; the equation read but should have read. The error has been corrected in the HTML and PDF versions of the article. Read More

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http://dx.doi.org/10.1038/s41588-019-0369-zDOI Listing
February 2019

3D genome shows its stripes in gene-rich regions.

Nat Rev Genet 2019 Feb 20. Epub 2019 Feb 20.

Associate Editor, Nature Communications, .

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http://dx.doi.org/10.1038/s41576-019-0102-xDOI Listing
February 2019

Fast Estimation of Recombination Rates Using Topological Data Analysis.

Genetics 2019 Feb 20. Epub 2019 Feb 20.

The University of Texas at Austin.

Accurate estimation of recombination rates is critical for studying the origins and maintenance of genetic diversity. Because the inference of recombination rates under a full evolutionary model is computationally expensive, an alternative approach using topological data analysis (TDA) on genome sequences has been developed. We find that this method can analyze datasets larger than what can be handled by any existing recombination inference software, and has accuracy comparable to commonly used model-based methods with significantly less processing time. Read More

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http://dx.doi.org/10.1534/genetics.118.301565DOI Listing
February 2019

Layers of Cryptic Genetic Variation Underlie a Yeast Complex Trait.

Genetics 2019 Feb 20. Epub 2019 Feb 20.

University of Southern California

Cryptic genetic variation may be an important contributor to heritable traits, but its extent and regulation are not fully understood. Here, we investigate the cryptic genetic variation underlying a colony phenotype that is typically suppressed in a cross of the lab strain BY4716 (BY) and a derivative of the clinical isolate 322134S (3S). To do this, we comprehensively dissect the trait's genetic basis in the BYx3S cross in the presence of three different genetic perturbations that enable its expression. Read More

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http://dx.doi.org/10.1534/genetics.119.301907DOI Listing
February 2019

Getting the drop on chromatin interaction.

Authors:
Linda Koch

Nat Rev Genet 2019 Feb 19. Epub 2019 Feb 19.

Nature Reviews Genetics, .

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http://dx.doi.org/10.1038/s41576-019-0103-9DOI Listing
February 2019

The Effects of Demography and Genetics on the Neutral Distribution of Quantitative Traits.

Authors:
Evan M Koch

Genetics 2019 Feb 19. Epub 2019 Feb 19.

University of Chicago

Neutral models for quantitative trait evolution are useful for identifying phenotypes under selection. These models often assume normally distributed phenotypes. This assumption may be violated when a trait is affected by relatively few variants or when the effects of those variants arise from skewed or heavy-tailed distributions. Read More

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http://dx.doi.org/10.1534/genetics.118.301839DOI Listing
February 2019

A Receptor Tyrosine Kinase Network Regulates Neuromuscular Function in Response to Oxidative Stress in .

Genetics 2019 Feb 19. Epub 2019 Feb 19.

University of Southern California

The transcription factor Nrf2 plays a critical role in the organism wide-regulation of the antioxidant stress response. The Nrf2 homolog SKN-1 functions in the intestine cell non-autonomously to negatively regulate neuromuscular (NMJ) function in To identify additional molecules that mediate SKN-1 signaling to the NMJ, we performed a candidate screen for suppressors of aldicarb-resistance caused by acute treatment with the SKN-1 activator, arsenite. We identified two receptor tyrosine kinases, EGL-15 (fibroblast growth factor receptor, FGFR) and DAF-2 (insulin-like peptide receptor, IR) that are required for NMJ regulation in response to stress. Read More

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http://dx.doi.org/10.1534/genetics.119.302026DOI Listing
February 2019

No genetic erosion after five generations for Impatiens glandulifera populations across the invaded range in Europe.

BMC Genet 2019 Feb 19;20(1):20. Epub 2019 Feb 19.

Department of Biology, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7034, Trondheim, Norway.

Background: The observation that many alien species become invasive despite low genetic diversity has long been considered the 'genetic paradox' in invasion biology. This paradox is often resolved through the temporal buildup genetic diversity through multiple introduction events. These temporal dynamics in genetic diversity are especially important for annual invasive plants that lack a persistent seed bank, for which population persistence is strongly dependent on consecutive seed 're-establishment' in each growing season. Read More

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http://dx.doi.org/10.1186/s12863-019-0721-4DOI Listing
February 2019

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Authors:
Anne E Justice Tugce Karaderi Heather M Highland Kristin L Young Mariaelisa Graff Yingchang Lu Valérie Turcot Paul L Auer Rebecca S Fine Xiuqing Guo Claudia Schurmann Adelheid Lempradl Eirini Marouli Anubha Mahajan Thomas W Winkler Adam E Locke Carolina Medina-Gomez Tõnu Esko Sailaja Vedantam Ayush Giri Ken Sin Lo Tamuno Alfred Poorva Mudgal Maggie C Y Ng Nancy L Heard-Costa Mary F Feitosa Alisa K Manning Sara M Willems Suthesh Sivapalaratnam Goncalo Abecasis Dewan S Alam Matthew Allison Philippe Amouyel Zorayr Arzumanyan Beverley Balkau Lisa Bastarache Sven Bergmann Lawrence F Bielak Matthias Blüher Michael Boehnke Heiner Boeing Eric Boerwinkle Carsten A Böger Jette Bork-Jensen Erwin P Bottinger Donald W Bowden Ivan Brandslund Linda Broer Amber A Burt Adam S Butterworth Mark J Caulfield Giancarlo Cesana John C Chambers Daniel I Chasman Yii-Der Ida Chen Rajiv Chowdhury Cramer Christensen Audrey Y Chu Francis S Collins James P Cook Amanda J Cox David S Crosslin John Danesh Paul I W de Bakker Simon de Denus Renée de Mutsert George Dedoussis Ellen W Demerath Joe G Dennis Josh C Denny Emanuele Di Angelantonio Marcus Dörr Fotios Drenos Marie-Pierre Dubé Alison M Dunning Douglas F Easton Paul Elliott Evangelos Evangelou Aliki-Eleni Farmaki Shuang Feng Ele Ferrannini Jean Ferrieres Jose C Florez Myriam Fornage Caroline S Fox Paul W Franks Nele Friedrich Wei Gan Ilaria Gandin Paolo Gasparini Vilmantas Giedraitis Giorgia Girotto Mathias Gorski Harald Grallert Niels Grarup Megan L Grove Stefan Gustafsson Jeff Haessler Torben Hansen Andrew T Hattersley Caroline Hayward Iris M Heid Oddgeir L Holmen G Kees Hovingh Joanna M M Howson Yao Hu Yi-Jen Hung Kristian Hveem M Arfan Ikram Erik Ingelsson Anne U Jackson Gail P Jarvik Yucheng Jia Torben Jørgensen Pekka Jousilahti Johanne M Justesen Bratati Kahali Maria Karaleftheri Sharon L R Kardia Fredrik Karpe Frank Kee Hidetoshi Kitajima Pirjo Komulainen Jaspal S Kooner Peter Kovacs Bernhard K Krämer Kari Kuulasmaa Johanna Kuusisto Markku Laakso Timo A Lakka David Lamparter Leslie A Lange Claudia Langenberg Eric B Larson Nanette R Lee Wen-Jane Lee Terho Lehtimäki Cora E Lewis Huaixing Li Jin Li Ruifang Li-Gao Li-An Lin Xu Lin Lars Lind Jaana Lindström Allan Linneberg Ching-Ti Liu Dajiang J Liu Jian'an Luan Leo-Pekka Lyytikäinen Stuart MacGregor Reedik Mägi Satu Männistö Gaëlle Marenne Jonathan Marten Nicholas G D Masca Mark I McCarthy Karina Meidtner Evelin Mihailov Leena Moilanen Marie Moitry Dennis O Mook-Kanamori Anna Morgan Andrew P Morris Martina Müller-Nurasyid Patricia B Munroe Narisu Narisu Christopher P Nelson Matt Neville Ioanna Ntalla Jeffrey R O'Connell Katharine R Owen Oluf Pedersen Gina M Peloso Craig E Pennell Markus Perola James A Perry John R B Perry Tune H Pers Ailith Ewing Ozren Polasek Olli T Raitakari Asif Rasheed Chelsea K Raulerson Rainer Rauramaa Dermot F Reilly Alex P Reiner Paul M Ridker Manuel A Rivas Neil R Robertson Antonietta Robino Igor Rudan Katherine S Ruth Danish Saleheen Veikko Salomaa Nilesh J Samani Pamela J Schreiner Matthias B Schulze Robert A Scott Marcelo Segura-Lepe Xueling Sim Andrew J Slater Kerrin S Small Blair H Smith Jennifer A Smith Lorraine Southam Timothy D Spector Elizabeth K Speliotes Kari Stefansson Valgerdur Steinthorsdottir Kathleen E Stirrups Konstantin Strauch Heather M Stringham Michael Stumvoll Liang Sun Praveen Surendran Karin M A Swart Jean-Claude Tardif Kent D Taylor Alexander Teumer Deborah J Thompson Gudmar Thorleifsson Unnur Thorsteinsdottir Betina H Thuesen Anke Tönjes Mina Torres Emmanouil Tsafantakis Jaakko Tuomilehto André G Uitterlinden Matti Uusitupa Cornelia M van Duijn Mauno Vanhala Rohit Varma Sita H Vermeulen Henrik Vestergaard Veronique Vitart Thomas F Vogt Dragana Vuckovic Lynne E Wagenknecht Mark Walker Lars Wallentin Feijie Wang Carol A Wang Shuai Wang Nicholas J Wareham Helen R Warren Dawn M Waterworth Jennifer Wessel Harvey D White Cristen J Willer James G Wilson Andrew R Wood Ying Wu Hanieh Yaghootkar Jie Yao Laura M Yerges-Armstrong Robin Young Eleftheria Zeggini Xiaowei Zhan Weihua Zhang Jing Hua Zhao Wei Zhao He Zheng Wei Zhou M Carola Zillikens Fernando Rivadeneira Ingrid B Borecki J Andrew Pospisilik Panos Deloukas Timothy M Frayling Guillaume Lettre Karen L Mohlke Jerome I Rotter Zoltán Kutalik Joel N Hirschhorn L Adrienne Cupples Ruth J F Loos Kari E North Cecilia M Lindgren

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Read More

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http://dx.doi.org/10.1038/s41588-018-0334-2DOI Listing
February 2019
29.352 Impact Factor

Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis.

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX, USA.

Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. Read More

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http://dx.doi.org/10.1038/s41588-018-0343-1DOI Listing
February 2019

Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases.

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Read More

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http://dx.doi.org/10.1038/s41588-019-0350-xDOI Listing
February 2019
29.352 Impact Factor

Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction.

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Characterizing the stem cells responsible for lung repair and regeneration is important for the treatment of pulmonary diseases. Recently, a unique cell population located at the bronchioalveolar-duct junctions has been proposed to comprise endogenous stem cells for lung regeneration. However, the role of bronchioalveolar stem cells (BASCs) in vivo remains debated, and the contribution of such cells to lung regeneration is not known. Read More

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http://www.nature.com/articles/s41588-019-0346-6
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http://dx.doi.org/10.1038/s41588-019-0346-6DOI Listing
February 2019
1 Read

Subcongenic analysis of a quantitative trait locus affecting body weight and glucose metabolism in zinc transporter 7 (znt7)-knockout mice.

BMC Genet 2019 Feb 18;20(1):19. Epub 2019 Feb 18.

Department of Nutrition, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA.

Background: A genome-wide mapping study using male F zinc transporter 7-knockout mice (znt7-KO) and their wild type littermates in a mixed 129P1/ReJ (129P1) and C57BL/6J (B6) background identified a quantitative trait locus (QTL) on chromosome 7, which had a synergistic effect on body weight gain and fat deposit with the znt7-null mutation.

Results: The genetic segment for body weight on mouse chromosome 7 was investigated by newly created subcongenic znt7-KO mouse strains carrying different lengths of genomic segments of chromosome 7 from the 129P1 donor strain in the B6 background. We mapped the sub-QTL for body weight in the proximal region of the previously mapped QTL, ranging from 47. Read More

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https://bmcgenet.biomedcentral.com/articles/10.1186/s12863-0
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http://dx.doi.org/10.1186/s12863-019-0715-2DOI Listing
February 2019
1 Read

Twenty-Seven Tamoxifen-Inducible iCre-Driver Mouse Strains for Eye and Brain; Including Seventeen Carrying a New Inducible-First Constitutive-Ready Allele.

Genetics 2019 Feb 14. Epub 2019 Feb 14.

University of British Columbia

To understand gene function, the cre/loxP conditional system is the most powerful available for temporal and spatial control of expression in mouse. However, the research community requires more cre recombinase expressing transgenic mouse strains (cre-drivers), which restrict expression to specific cell types. To address these problems, a high-throughput method for large-scale production that produces high-quality results is necessary. Read More

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http://dx.doi.org/10.1534/genetics.119.301984DOI Listing
February 2019

Characterization of the extra copy of TPOX locus with tri-allelic pattern.

BMC Genet 2019 Feb 14;20(1):18. Epub 2019 Feb 14.

Department of Forensic Medicine, Shanghai Medical College of Fudan University, Shanghai, 200032, China.

Background: An STR locus with tri-allelic pattern is occasionally observed in routine forensic casework. The extra copy of TPOX locus with tri-allelic pattern in populations has been assumed to be inserted into an X chromosome, which took place forth before the Bantu expansion in Africa. Nonetheless, the exact location of the duplication and the form of rearrangement in the human genome has not been clarified yet. Read More

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http://dx.doi.org/10.1186/s12863-019-0723-2DOI Listing
February 2019

The epigenetic regulation of HsMar1, a human DNA transposon.

BMC Genet 2019 Feb 14;20(1):17. Epub 2019 Feb 14.

EA 6306 Instabilité génétique et cancer, Université de Tours, UFR Sciences et Techniques, UFR Pharmacie, 31 Avenue Monge, 37200, Tours, France.

Background: Both classes of transposable elements (DNA and RNA) are tightly regulated at the transcriptional level leading to the inactivation of transposition via epigenetic mechanisms. Due to the high copies number of these elements, the hypothesis has emerged that their regulation can coordinate a regulatory network of genes. Herein, we investigated whether transposition regulation of HsMar1, a human DNA transposon, differs in presence or absence of endogenous HsMar1 copies. Read More

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http://dx.doi.org/10.1186/s12863-019-0719-yDOI Listing
February 2019

Telomeres and telomerase: three decades of progress.

Nat Rev Genet 2019 Feb 13. Epub 2019 Feb 13.

Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA.

Many recent advances have emerged in the telomere and telomerase fields. This Timeline article highlights the key advances that have expanded our views on the mechanistic underpinnings of telomeres and telomerase and their roles in ageing and disease. Three decades ago, the classic view was that telomeres protected the natural ends of linear chromosomes and that telomerase was a specific telomere-terminal transferase necessary for the replication of chromosome ends in single-celled organisms. Read More

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http://dx.doi.org/10.1038/s41576-019-0099-1DOI Listing
February 2019

Dissection of Complex, Fitness-Related Traits in Multiple Mapping Populations Offers Insight into the Genetic Control of Stress Resistance.

Genetics 2019 Feb 13. Epub 2019 Feb 13.

University of Kansas

We leverage two complementary mapping panels to genetically dissect starvation resistance, an important fitness trait. Using >1600 genotypes from the multiparental Synthetic Population Resource (DSPR) we map numerous starvation stress QTL that collectively explain a substantial fraction of trait heritability. Mapped QTL effects allowed us to estimate DSPR founder phenotypes, predictions that were correlated with the actual phenotypes of these lines. Read More

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http://dx.doi.org/10.1534/genetics.119.301930DOI Listing
February 2019

Long-Term Population Studies Uncover the Genome Structure and Genetic Basis of Xenobiotic and Host Plant Adaptation in the Herbivore .

Genetics 2019 Feb 11. Epub 2019 Feb 11.

University of Utah

Pesticide resistance arises rapidly in arthropod herbivores, as can host plant adaptation, and both are significant problems in agriculture. These traits have been challenging to study as both are often polygenic and many arthropods are genetically intractable. Here, we examined the genetic architecture of pesticide resistance and host plant adaptation in the two-spotted spider mite, a global agricultural pest. Read More

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http://dx.doi.org/10.1534/genetics.118.301803DOI Listing
February 2019

Landscape of B cell immunity and related immune evasion in human cancers.

Nat Genet 2019 Feb 11. Epub 2019 Feb 11.

Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Read More

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http://dx.doi.org/10.1038/s41588-018-0339-xDOI Listing
February 2019
1 Read
29.352 Impact Factor

Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration.

Nat Genet 2019 Feb 11. Epub 2019 Feb 11.

Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Genome-wide association studies (GWAS) have identified genetic variants at 34 loci contributing to age-related macular degeneration (AMD). We generated transcriptional profiles of postmortem retinas from 453 controls and cases at distinct stages of AMD and integrated retinal transcriptomes, covering 13,662 protein-coding and 1,462 noncoding genes, with genotypes at more than 9 million common SNPs for expression quantitative trait loci (eQTL) analysis of a tissue not included in Genotype-Tissue Expression (GTEx) and other large datasets. Cis-eQTL analysis identified 10,474 genes under genetic regulation, including 4,541 eQTLs detected only in the retina. Read More

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http://dx.doi.org/10.1038/s41588-019-0351-9DOI Listing
February 2019
29.352 Impact Factor

A new Cas in town.

Authors:
Linda Koch

Nat Rev Genet 2019 Feb 8. Epub 2019 Feb 8.

Nature Reviews Genetics, .

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http://dx.doi.org/10.1038/s41576-019-0101-yDOI Listing
February 2019

Induced pluripotent stem cells in disease modelling and drug discovery.

Nat Rev Genet 2019 Feb 8. Epub 2019 Feb 8.

Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

The derivation of induced pluripotent stem cells (iPSCs) over a decade ago sparked widespread enthusiasm for the development of new models of human disease, enhanced platforms for drug discovery and more widespread use of autologous cell-based therapy. Early studies using directed differentiation of iPSCs frequently uncovered cell-level phenotypes in monogenic diseases, but translation to tissue-level and organ-level diseases has required development of more complex, 3D, multicellular systems. Organoids and human-rodent chimaeras more accurately mirror the diverse cellular ecosystems of complex tissues and are being applied to iPSC disease models to recapitulate the pathobiology of a broad spectrum of human maladies, including infectious diseases, genetic disorders and cancer. Read More

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http://dx.doi.org/10.1038/s41576-019-0100-zDOI Listing
February 2019

Uncovering a multitude of human glucocorticoid receptor variants: an expansive survey of a single gene.

BMC Genet 2019 Feb 8;20(1):16. Epub 2019 Feb 8.

Shriners Hospitals for Children Northern California, Sacramento, California, USA.

Background: Glucocorticoids are commonly used in the clinical setting for their potent anti-inflammatory effects; however, significant variations in response to treatment have been demonstrated. Although the underlying mechanisms have yet to be fully understood, this variable response may be a result of alterations in human glucocorticoid receptor (hGR) expression and function. In addition to hGRα, the biologically active isoform, a screening of current databases and publications revealed five alternative splice isoforms and hundreds of variants that have been reported to date. Read More

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http://dx.doi.org/10.1186/s12863-019-0718-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368729PMC
February 2019

as a Genetic Model for Hematopoiesis.

Genetics 2019 02;211(2):367-417

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California 90095

In this FlyBook chapter, we present a survey of the current literature on the development of the hematopoietic system in The blood system consists entirely of cells that function in innate immunity, tissue integrity, wound healing, and various forms of stress response, and are therefore functionally similar to myeloid cells in mammals. The primary cell types are specialized for phagocytic, melanization, and encapsulation functions. As in mammalian systems, multiple sites of hematopoiesis are evident in and the mechanisms involved in this process employ many of the same molecular strategies that exemplify blood development in humans. Read More

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http://dx.doi.org/10.1534/genetics.118.300223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366919PMC
February 2019
1 Read

Illuminating Women's Hidden Contribution to Historical Theoretical Population Genetics.

Genetics 2019 02;211(2):363-366

Department of Biology, San Francisco State University, California 94132

While productivity in academia is measured through authorship, not all scientific contributors have been recognized as authors. We consider nonauthor "acknowledged programmers" (APs), who developed, ran, and sometimes analyzed the results of computer programs. We identified APs in articles published between 1970 and 1990, finding that APs were disproportionately women ( = 4. Read More

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http://dx.doi.org/10.1534/genetics.118.301277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366915PMC
February 2019

Modulation of Gene Silencing by Cdc7p via H4 K16 Acetylation and Phosphorylation of Chromatin Assembly Factor CAF-1 in .

Genetics 2019 Feb 6. Epub 2019 Feb 6.

Purdue University

CAF-1 is an evolutionarily conserved H3/H4 histone chaperone that plays a key role in replication-coupled chromatin assembly and is targeted to the replication fork via interactions with PCNA, which, if disrupted, leads to epigenetic defects. In , when the silent mating-type locus contains point mutations within the silencer, Sir protein association and silencing is lost. Mutation of encoding an S phase-specific kinase, or subunits of the H4 K16-specific acetyltransferase complex SAS-I, however, restore silencing to this crippled , Here, we observed that loss of Cac1p, the largest subunit of CAF-1, also restores silencing at and silencing in both Δ and mutants is suppressed by overexpression of We demonstrate Cdc7p and Cac1p interact in S phase, but not G1, consistent with observed cell cycle-dependent phosphorylation of Cac1p, and hypoacetylation of chromatin at H4 K16 in both and Δ mutants. Read More

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http://dx.doi.org/10.1534/genetics.118.301858DOI Listing
February 2019

The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic.

Nat Genet 2019 Feb 4. Epub 2019 Feb 4.

MRC cancer unit, Hutchison/MRC research Centre, University of Cambridge, Cambridge, UK.

Esophageal adenocarcinoma (EAC) is a poor-prognosis cancer type with rapidly rising incidence. Understanding of the genetic events driving EAC development is limited, and there are few molecular biomarkers for prognostication or therapeutics. Using a cohort of 551 genomically characterized EACs with matched RNA sequencing data, we discovered 77 EAC driver genes and 21 noncoding driver elements. Read More

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http://www.nature.com/articles/s41588-018-0331-5
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http://dx.doi.org/10.1038/s41588-018-0331-5DOI Listing
February 2019
1 Read

Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.

Nat Genet 2019 Feb 4. Epub 2019 Feb 4.

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

To understand the genetics of type 2 diabetes in people of Japanese ancestry, we conducted A meta-analysis of four genome-wide association studies (GWAS; 36,614 cases and 155,150 controls of Japanese ancestry). We identified 88 type 2 diabetes-associated loci (P < 5.0 × 10) with 115 independent signals (P < 5. Read More

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http://www.nature.com/articles/s41588-018-0332-4
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http://dx.doi.org/10.1038/s41588-018-0332-4DOI Listing
February 2019
2 Reads

Integration of Self and Non-self Recognition Modulates Asexual Cell-to-Cell Communication in .

Genetics 2019 Feb 4. Epub 2019 Feb 4.

The University of California, Berkeley; The Lawrence Berkeley National Laboratory

Cells rarely exist alone, which drives the evolution of diverse mechanisms for identifying and responding appropriately to the presence of other nearby cells. Filamentous fungi depend on somatic cell-to-cell communication and fusion for the development and maintenance of a multicellular, interconnected colony that is characteristic of this group of organisms. The filamentous fungus is a model for investigating the mechanisms of somatic cell-to-cell communication and fusion. Read More

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http://dx.doi.org/10.1534/genetics.118.301780DOI Listing
February 2019

Distribution of Proteins at the Inner Nuclear Membrane Is Regulated by the Asi1 E3 Ligase in .

Genetics 2019 Feb 1. Epub 2019 Feb 1.

Stowers Institute for Medical Research; University of Kansas Medical Center

Inner nuclear membrane (INM) protein composition regulates nuclear function, affecting processes such as gene expression, chromosome organization, nuclear shape and stability. Mechanisms that drive changes in the INM proteome are poorly understood in part because it is difficult to definitively assay INM composition rigorously and systematically. Using a split-GFP complementation system to detect INM access, we examined the distribution of all C-terminally tagged membrane proteins in wild-type cells and in mutants affecting protein quality control pathways, such as INM-associated degradation (INMAD), ER-associated degradation (ERAD) and vacuolar proteolysis. Read More

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http://dx.doi.org/10.1534/genetics.119.301911DOI Listing
February 2019

Genomics and our future food security.

Authors:

Nat Genet 2019 Feb;51(2):197

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http://dx.doi.org/10.1038/s41588-019-0352-8DOI Listing
February 2019

Interference Effects of Deleterious and Beneficial Mutations in Large Asexual Populations.

Authors:
Kavita Jain

Genetics 2019 Jan 30. Epub 2019 Jan 30.

Jawaharlal Nehru Centre for Advanced Scientific Research

Linked beneficial and deleterious mutations are known to decrease the fixation probability of a favorable mutation in large asexual populations. While the hindering effect of strongly deleterious mutations on adaptive evolution has been well studied, how weakly deleterious mutations, either in isolation or with superior beneficial mutations, influence the rate of adaptation has not been fully explored. When the selection against the deleterious mutations is weak, the beneficial mutant can fix in many genetic backgrounds, besides the one it arose on. Read More

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http://www.genetics.org/lookup/doi/10.1534/genetics.119.3019
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http://dx.doi.org/10.1534/genetics.119.301960DOI Listing
January 2019
2 Reads

Purine Homeostasis Is Necessary for Developmental Timing, Germline Maintenance and Muscle Integrity in .

Genetics 2019 Jan 30. Epub 2019 Jan 30.

Université de Bordeaux and CNRS UMR5095

Purine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized , reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Although thoroughly characterized in microorganisms, such as yeast or bacteria, little is known about the regulation of the purine biosynthesis network in metazoans. Read More

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http://dx.doi.org/10.1534/genetics.118.301062DOI Listing
January 2019
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Necessity and Contingency in Developmental Genetic Screens: EGF, Wnt and Semaphorin Pathways in Vulval Induction of the Nematode .

Genetics 2019 Jan 30. Epub 2019 Jan 30.

PSL Research University

Genetic screens in the nematode s identified the EGF/Ras and Notch pathways as central for vulval precursor cell fate patterning. Schematically, the anchor cell secretes EGF, inducing the P6.p cell to a 1° vulval fate; P6. Read More

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http://dx.doi.org/10.1534/genetics.119.301970DOI Listing
January 2019
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Integrative single-cell analysis.

Nat Rev Genet 2019 Jan 29. Epub 2019 Jan 29.

New York Genome Center, New York, NY, USA.

The recent maturation of single-cell RNA sequencing (scRNA-seq) technologies has coincided with transformative new methods to profile genetic, epigenetic, spatial, proteomic and lineage information in individual cells. This provides unique opportunities, alongside computational challenges, for integrative methods that can jointly learn across multiple types of data. Integrated analysis can discover relationships across cellular modalities, learn a holistic representation of the cell state, and enable the pooling of data sets produced across individuals and technologies. Read More

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http://dx.doi.org/10.1038/s41576-019-0093-7DOI Listing
January 2019

Author Correction: Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism.

Nat Genet 2019 Jan 29. Epub 2019 Jan 29.

Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK.

In the version of this article initially published, in Table 2, the descriptions of pathways and definitions in the first and last columns did not correctly correspond to the values in the other columns. The error has been corrected in the HTML and PDF versions of the article. Read More

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http://dx.doi.org/10.1038/s41588-019-0357-3DOI Listing
January 2019

Sequence Characteristics Distinguish Transcribed Enhancers from Promoters and Predict Their Breadth of Activity.

Genetics 2019 Jan 29. Epub 2019 Jan 29.

Vanderbilt University

Enhancers and promoters both regulate gene expression by recruiting transcription factors; however, the degree to which enhancer vs. promoter activity is due to differences in their sequences or to genomic context is the subject of ongoing debate. We examined this question by analyzing the sequences of thousands of transcribed enhancers and promoters from hundreds of cellular contexts previously identified by Cap Analysis of Gene Expression (CAGE). Read More

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http://dx.doi.org/10.1534/genetics.118.301895DOI Listing
January 2019

Efficient Generation of Endogenous Fluorescent Reporters by Nested CRISPR in .

Genetics 2019 Jan 29. Epub 2019 Jan 29.

L'Hospitalet de Llobregat

CRISPR-based genome editing methods in model organisms are evolving at an extraordinary speed. Whereas the generation of deletion or missense mutants is quite straightforward, the production of endogenous fluorescent reporters is more challenging. We have developed Nested CRISPR, a cloning-free ribonucleoprotein-driven method that robustly produces endogenous fluorescent reporters with EGFP, mCherry, or wrmScarlet in This method is based on the division of the fluorescent protein (FP) sequence in three fragments. Read More

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http://dx.doi.org/10.1534/genetics.119.301965DOI Listing
January 2019

Evolutionary Rescue Through Partly Heritable Phenotypic Variability.

Genetics 2019 Jan 29. Epub 2019 Jan 29.

University of Pennsylvania.

Environmental variation is commonplace, but unpredictable. Populations that encounter a deleterious environment can sometimes avoid extinction by rapid evolutionary adaptation. Phenotypic variability, whereby a single genotype can express multiple different phenotypes, might play an important role in rescuing such populations from extinction. Read More

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http://www.genetics.org/lookup/doi/10.1534/genetics.118.3017
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http://dx.doi.org/10.1534/genetics.118.301758DOI Listing
January 2019
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The main WAP isoform usually found in camel milk arises from the usage of an improbable intron cryptic splice site in the precursor to mRNA in which a GC-AG intron occurs.

BMC Genet 2019 Jan 29;20(1):14. Epub 2019 Jan 29.

INRA, UMR GABI, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.

Background: Whey acidic protein (WAP) is a major protein identified in the milk of several mammalian species with cysteine-rich domains known as four-disulfide cores (4-DSC). The organization of the eutherian WAP genes is highly conserved through evolution. It has been proposed that WAP could play an important role in regulating the proliferation of mammary epithelial cells. Read More

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http://dx.doi.org/10.1186/s12863-018-0704-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350295PMC
January 2019

Dissecting closely linked association signals in combination with the mammalian phenotype database can identify candidate genes in dairy cattle.

BMC Genet 2019 Jan 29;20(1):15. Epub 2019 Jan 29.

Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, 8830, Tjele, Denmark.

Background: Genome-wide association studies (GWAS) have been successfully implemented in cattle research and breeding. However, moving from the associations to identify the causal variants and reveal underlying mechanisms have proven complicated. In dairy cattle populations, we face a challenge due to long-range linkage disequilibrium (LD) arising from close familial relationships in the studied individuals. Read More

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https://bmcgenet.biomedcentral.com/articles/10.1186/s12863-0
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http://dx.doi.org/10.1186/s12863-019-0717-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350337PMC
January 2019
2 Reads

Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population.

Nat Genet 2019 Jan 28. Epub 2019 Jan 28.

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.

To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (n = 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype-phenotype associations across 52 phenotypes. Read More

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http://dx.doi.org/10.1038/s41588-018-0336-0DOI Listing
January 2019
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EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains.

Nat Genet 2019 Jan 28. Epub 2019 Jan 28.

Swiss Institute for Experimental Cancer Research (ISREC), School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Chromatin is organized into topologically associating domains (TADs) enriched in distinct histone marks. In cancer, gain-of-function mutations in the gene encoding the enhancer of zeste homolog 2 protein (EZH2) lead to a genome-wide increase in histone-3 Lys27 trimethylation (H3K27me3) associated with transcriptional repression. However, the effects of these epigenetic changes on the structure and function of chromatin domains have not been explored. Read More

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http://www.nature.com/articles/s41588-018-0338-y
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http://dx.doi.org/10.1038/s41588-018-0338-yDOI Listing
January 2019
4 Reads

GARFIELD classifies disease-relevant genomic features through integration of functional annotations with association signals.

Nat Genet 2019 Feb 28;51(2):343-353. Epub 2019 Jan 28.

Human Genetics, Wellcome Sanger Institute, Hinxton, UK.

Loci discovered by genome-wide association studies predominantly map outside protein-coding genes. The interpretation of the functional consequences of non-coding variants can be greatly enhanced by catalogs of regulatory genomic regions in cell lines and primary tissues. However, robust and readily applicable methods are still lacking by which to systematically evaluate the contribution of these regions to genetic variation implicated in diseases or quantitative traits. Read More

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http://dx.doi.org/10.1038/s41588-018-0322-6DOI Listing
February 2019

A Shift in Aggregation Avoidance Strategy Marks a Long-Term Direction to Protein Evolution.

Genetics 2019 Jan 28. Epub 2019 Jan 28.

University of Arizona

To detect a direction to evolution, without the pitfalls of reconstructing ancestral states, we need to compare "more evolved" to "less evolved" entities. But because all extant species have the same common ancestor, none are chronologically more evolved than any other. However, different gene families were born at different times, allowing us to compare young protein-coding genes to those that are older and hence have been evolving for longer. Read More

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http://www.genetics.org/lookup/doi/10.1534/genetics.118.3017
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http://dx.doi.org/10.1534/genetics.118.301719DOI Listing
January 2019
2 Reads

Adjusting for Principal Components of Molecular Phenotypes Induces Replicating False Positives.

Genetics 2019 Jan 28. Epub 2019 Jan 28.

University of California San Francisco.

High-throughput measurements of molecular phenotypes provide an unprecedented opportunity to model cellular processes and their impact on disease. These highly-structured datasets are usually strongly confounded, creating false positives and reducing power. This has motivated many approaches based on principal components analysis (PCA) to estimate and correct for confounders, which have become indispensable elements of association tests between molecular phenotypes and both genetic and non-genetic factors. Read More

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http://dx.doi.org/10.1534/genetics.118.301768DOI Listing
January 2019