31,752 results match your criteria GENETICS [Journal]


Author Correction: Transposable elements drive widespread expression of oncogenes in human cancers.

Nat Genet 2019 Apr 16. Epub 2019 Apr 16.

Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.

In the version of this article initially published, grant PF-17-201-01-TBG from the American Cancer Society to author Erica C. Pehrsson was not included in the Acknowledgements. 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/s41588-019-0416-9DOI Listing

The Role of Tissue Inhibitors of Metalloproteinases in Organ Development and Regulation of ADAMTS Family Metalloproteinases in .

Genetics 2019 Apr 16. Epub 2019 Apr 16.

Tohoku University.

Remodeling of the extracellular matrix supports tissue and organ development by regulating cellular morphology and tissue integrity. However, proper extracellular matrix remodeling requires spatiotemporal regulation of extracellular metalloproteinase activity. Members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, including MIG-17 and GON-1, are evolutionarily conserved, secreted zinc-requiring metalloproteinases. Read More

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http://dx.doi.org/10.1534/genetics.119.301795DOI Listing

Author Correction: An atlas of genetic influences on osteoporosis in humans and mice.

Nat Genet 2019 Apr 15. Epub 2019 Apr 15.

Department of Human Genetics, McGill University, Montréal, Québec, Canada.

In the version of this article initially published, in Fig. 5a, the data in the right column of 'DAAM2 gRNA1' were incorrectly plotted as circles indicating 'untreated' rather than as squares indicating 'treated'. The error has been corrected in the HTML and PDF versions of the article. Read More

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http://www.nature.com/articles/s41588-019-0415-x
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http://dx.doi.org/10.1038/s41588-019-0415-xDOI Listing
April 2019
1 Read

Detecting the mutational signature of homologous recombination deficiency in clinical samples.

Nat Genet 2019 Apr 15. Epub 2019 Apr 15.

Department of Biomedical Informatics and Ludwig Center at Harvard, Harvard Medical School, Boston, MA, USA.

Mutations in BRCA1 and/or BRCA2 (BRCA1/2) are the most common indication of deficiency in the homologous recombination (HR) DNA repair pathway. However, recent genome-wide analyses have shown that the same pattern of mutations found in BRCA1/2-mutant tumors is also present in several other tumors. Here, we present a new computational tool called Signature Multivariate Analysis (SigMA), which can be used to accurately detect the mutational signature associated with HR deficiency from targeted gene panels. Read More

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http://www.nature.com/articles/s41588-019-0390-2
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http://dx.doi.org/10.1038/s41588-019-0390-2DOI Listing
April 2019
4 Reads

A reinforcing HNF4-SMAD4 feed-forward module stabilizes enterocyte identity.

Nat Genet 2019 Apr 15. Epub 2019 Apr 15.

Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.

BMP/SMAD signaling is a crucial regulator of intestinal differentiation. However, the molecular underpinnings of the BMP pathway in this context are unknown. Here, we characterize the mechanism by which BMP/SMAD signaling drives enterocyte differentiation. Read More

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http://www.nature.com/articles/s41588-019-0384-0
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http://dx.doi.org/10.1038/s41588-019-0384-0DOI Listing
April 2019
1 Read

Evolution of buffering in a genetic circuit controlling plant stem cell proliferation.

Nat Genet 2019 Apr 15. Epub 2019 Apr 15.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

Precise control of plant stem cell proliferation is necessary for the continuous and reproducible development of plant organs. The peptide ligand CLAVATA3 (CLV3) and its receptor protein kinase CLAVATA1 (CLV1) maintain stem cell homeostasis within a deeply conserved negative feedback circuit. In Arabidopsis, CLV1 paralogs also contribute to homeostasis, by compensating for the loss of CLV1 through transcriptional upregulation. Read More

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http://www.nature.com/articles/s41588-019-0389-8
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http://dx.doi.org/10.1038/s41588-019-0389-8DOI Listing
April 2019
1 Read

Spatial transcriptomics coming of age.

Authors:
Darren J Burgess

Nat Rev Genet 2019 Apr 12. Epub 2019 Apr 12.

Nature Reviews Genetics, .

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http://dx.doi.org/10.1038/s41576-019-0129-zDOI Listing

Genetic Variation for Ontogenetic Shifts in Metabolism Underlies Physiological Homeostasis in .

Genetics 2019 Apr 11. Epub 2019 Apr 11.

University of Nebraska-Lincoln.

Organismal physiology emerges from metabolic pathways and subcellular structures like the mitochondria that can vary across development and among individuals. Here we tested whether genetic variation at one level of physiology can be buffered at higher biological levels of organization during development by the inherent capacity for homeostasis in physiological systems. We found that the fundamental scaling relationship between mass and metabolic rate, as well as the oxidative capacity per mitochondria, changed significantly across development in the fruit fly However, mitochondrial respiration rate was maintained at similar levels across development. Read More

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http://dx.doi.org/10.1534/genetics.119.302052DOI Listing

Microbial signatures of colorectal cancer.

Authors:
Linda Koch

Nat Rev Genet 2019 Apr 10. Epub 2019 Apr 10.

Nature Reviews Genetics, .

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http://dx.doi.org/10.1038/s41576-019-0126-2DOI Listing
April 2019
1 Read

Deep learning: new computational modelling techniques for genomics.

Nat Rev Genet 2019 Apr 10. Epub 2019 Apr 10.

Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.

As a data-driven science, genomics largely utilizes machine learning to capture dependencies in data and derive novel biological hypotheses. However, the ability to extract new insights from the exponentially increasing volume of genomics data requires more expressive machine learning models. By effectively leveraging large data sets, deep learning has transformed fields such as computer vision and natural language processing. Read More

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http://www.nature.com/articles/s41576-019-0122-6
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http://dx.doi.org/10.1038/s41576-019-0122-6DOI Listing
April 2019
3 Reads

Complex Trait Prediction from Genome Data: Contrasting EBV in Livestock to PRS in Humans: Genomic Prediction.

Genetics 2019 Apr;211(4):1131-1141

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia.

In this Review, we focus on the similarity of the concepts underlying prediction of estimated breeding values (EBVs) in livestock and polygenic risk scores (PRS) in humans. Our research spans both fields and so we recognize factors that are very obvious for those in one field, but less so for those in the other. Differences in family size between species is the wedge that drives the different viewpoints and approaches. Read More

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http://dx.doi.org/10.1534/genetics.119.301859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456317PMC

From R.A. Fisher's 1918 Paper to GWAS a Century Later.

Genetics 2019 Apr;211(4):1125-1130

Centre for AgriBioscience, Department of Economic Development, Jobs, Transport and Resources, Bundoora, Victoria, Australia 3083.

The genetics and evolution of complex traits, including quantitative traits and disease, have been hotly debated ever since Darwin. A century ago, a paper from R.A. Read More

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http://dx.doi.org/10.1534/genetics.118.301594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456325PMC

An integrative U method for joint analysis of multi-level omic data.

BMC Genet 2019 Apr 10;20(1):40. Epub 2019 Apr 10.

Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, 48824, USA.

Background: The advance of high-throughput technologies has made it cost-effective to collect diverse types of omic data in large-scale clinical and biological studies. While the collection of the vast amounts of multi-level omic data from these studies provides a great opportunity for genetic research, the high dimensionality of omic data and complex relationships among multi-level omic data bring tremendous analytic challenges.

Results: To address these challenges, we develop an integrative U (IU) method for the design and analysis of multi-level omic data. 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/s12863-019-0742-zDOI Listing
April 2019
2 Reads

Durum wheat genome highlights past domestication signatures and future improvement targets.

Nat Genet 2019 Apr 8. Epub 2019 Apr 8.

CREA-Research Centre for Genomics and Bioinformatics, Fiorenzuola d'Arda, Italy.

The domestication of wild emmer wheat led to the selection of modern durum wheat, grown mainly for pasta production. We describe the 10.45 gigabase (Gb) assembly of the genome of durum wheat cultivar Svevo. Read More

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http://dx.doi.org/10.1038/s41588-019-0381-3DOI Listing
April 2019
29.352 Impact Factor

Measuring intolerance to mutation in human genetics.

Nat Genet 2019 Apr 8. Epub 2019 Apr 8.

Department of Biological Sciences, Columbia University, New York, NY, USA.

In numerous applications, from working with animal models to mapping the genetic basis of human disease susceptibility, knowing whether a single disrupting mutation in a gene is likely to be deleterious is useful. With this goal in mind, a number of measures have been developed to identify genes in which protein-truncating variants (PTVs), or other types of mutations, are absent or kept at very low frequency in large population samples-genes that appear 'intolerant' to mutation. One measure in particular, the probability of being loss-of-function intolerant (pLI), has been widely adopted. Read More

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http://dx.doi.org/10.1038/s41588-019-0383-1DOI Listing

Ancient pathogen genomics as an emerging tool for infectious disease research.

Nat Rev Genet 2019 Apr 5. Epub 2019 Apr 5.

Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena, Germany.

Over the past decade, a genomics revolution, made possible through the development of high-throughput sequencing, has triggered considerable progress in the study of ancient DNA, enabling complete genomes of past organisms to be reconstructed. A newly established branch of this field, ancient pathogen genomics, affords an in-depth view of microbial evolution by providing a molecular fossil record for a number of human-associated pathogens. Recent accomplishments include the confident identification of causative agents from past pandemics, the discovery of microbial lineages that are now extinct, the extrapolation of past emergence events on a chronological scale and the characterization of long-term evolutionary history of microorganisms that remain relevant to public health today. Read More

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http://dx.doi.org/10.1038/s41576-019-0119-1DOI Listing

Gut microbial structural variation links to human health.

Authors:
Dorothy Clyde

Nat Rev Genet 2019 Apr 5. Epub 2019 Apr 5.

Nature Reviews Genetics, .

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http://dx.doi.org/10.1038/s41576-019-0124-4DOI Listing

NATF (Native And Tissue-Specific Fluorescence): A Strategy for Bright, Tissue-Specific GFP Labeling of Native Proteins in .

Genetics 2019 Apr 5. Epub 2019 Apr 5.

Vanderbilt University; Vanderbilt University School of Medicine

GFP labeling by genome editing can reveal the authentic location of a native protein but is frequently hampered by weak GFP signals and broad expression across a range of tissues that may obscure cell-specific localization. To overcome these problems, we engineered a ative nd issue-specific luorescence (NATF) strategy which combines CRISPR/Cas-9 and split-GFP to yield bright, cell-specific protein labeling. We use CRISPR/Cas9 to insert a tandem array of seven copies of the GFP11 ß-strand ( at the genomic locus of each target protein. Read More

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http://dx.doi.org/10.1534/genetics.119.302063DOI Listing

Divergent Allele Advantage Provides a Quantitative Model for Maintaining Alleles with a Wide Range of Intrinsic Merits.

Genetics 2019 Apr 5. Epub 2019 Apr 5.

University of Glasgow.

The Major Histocompatibility Complex (MHC) is the most genetically diverse region of the genome in most vertebrates. Some form of balancing selection is necessary to account for the extreme diversity, but the precise mechanism of balancing selection is unknown. Due to the way MHC molecules determine immune recognition, overdominance (also referred to as heterozygote advantage) has been suggested as the main driving force behind this unrivalled diversity. Read More

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http://dx.doi.org/10.1534/genetics.119.302022DOI Listing

Publisher Correction: Fgf10 is essential for limb and lung formation.

Nat Genet 2019 Apr 4. Epub 2019 Apr 4.

Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan.

In the version of the paper initially published, Fig. 5a was inadvertently duplicated and presented as both Fig. 5a and 5f, and the correct image for Fig. Read More

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http://dx.doi.org/10.1038/s41588-019-0396-9DOI Listing

The Role of Insulators in Transgene Transvection in .

Genetics 2019 Apr 4. Epub 2019 Apr 4.

Foundation for Research & Technology Hellas; University of Crete

Transvection is the phenomenon where a transcriptional enhancer activates a promoter located on the homologous chromosome. It has been amply documented in where homologues are closely paired in most, if not all, somatic nuclei, but it has been known to rarely occur in mammals as well. We have taken advantage of site-directed transgenesis to insert reporter constructs into the same genetic locus in and have evaluated their ability to engage in transvection by testing many heterozygous combinations. Read More

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http://dx.doi.org/10.1534/genetics.119.302165DOI Listing

When the elite compete.

Authors:
Linda Koch

Nat Rev Genet 2019 Apr 2. Epub 2019 Apr 2.

Nature Reviews Genetics, .

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http://dx.doi.org/10.1038/s41576-019-0123-5DOI Listing

: A Computational Workflow for Designing Libraries of Guide RNAs for CRISPR-Mediated Base Editing.

Genetics 2019 Apr 1. Epub 2019 Apr 1.

Université Laval.

CRISPR-mediated base editors have opened unique avenues for scar-free genome-wide mutagenesis. Here, we describe a comprehensive computational workflow called that can be broadly adapted for designing guide RNA libraries with a range of CRISPR-mediated base editors, PAM recognition sequences and genomes of many species. Additionally, in order to assist users in selecting the best sets of guide RNAs for their experiments, estimates, called scores are calculated. Read More

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http://dx.doi.org/10.1534/genetics.119.302089DOI Listing
April 2019
2 Reads

A duty to recontact in genetics: context matters.

Nat Rev Genet 2019 Apr 1. Epub 2019 Apr 1.

Department of Medical Humanities, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.

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http://dx.doi.org/10.1038/s41576-019-0121-7DOI Listing

Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.

Authors:
Amy R Bentley Yun J Sung Michael R Brown Thomas W Winkler Aldi T Kraja Ioanna Ntalla Karen Schwander Daniel I Chasman Elise Lim Xuan Deng Xiuqing Guo Jingmin Liu Yingchang Lu Ching-Yu Cheng Xueling Sim Dina Vojinovic Jennifer E Huffman Solomon K Musani Changwei Li Mary F Feitosa Melissa A Richard Raymond Noordam Jenna Baker Guanjie Chen Hugues Aschard Traci M Bartz Jingzhong Ding Rajkumar Dorajoo Alisa K Manning Tuomo Rankinen Albert V Smith Salman M Tajuddin Wei Zhao Mariaelisa Graff Maris Alver Mathilde Boissel Jin Fang Chai Xu Chen Jasmin Divers Evangelos Evangelou Chuan Gao Anuj Goel Yanick Hagemeijer Sarah E Harris Fernando P Hartwig Meian He Andrea R V R Horimoto Fang-Chi Hsu Yi-Jen Hung Anne U Jackson Anuradhani Kasturiratne Pirjo Komulainen Brigitte Kühnel Karin Leander Keng-Hung Lin Jian'an Luan Leo-Pekka Lyytikäinen Nana Matoba Ilja M Nolte Maik Pietzner Bram Prins Muhammad Riaz Antonietta Robino M Abdullah Said Nicole Schupf Robert A Scott Tamar Sofer Alena Stancáková Fumihiko Takeuchi Bamidele O Tayo Peter J van der Most Tibor V Varga Tzung-Dau Wang Yajuan Wang Erin B Ware Wanqing Wen Yong-Bing Xiang Lisa R Yanek Weihua Zhang Jing Hua Zhao Adebowale Adeyemo Saima Afaq Najaf Amin Marzyeh Amini Dan E Arking Zorayr Arzumanyan Tin Aung Christie Ballantyne R Graham Barr Lawrence F Bielak Eric Boerwinkle Erwin P Bottinger Ulrich Broeckel Morris Brown Brian E Cade Archie Campbell Mickaël Canouil Sabanayagam Charumathi Yii-Der Ida Chen Kaare Christensen Maria Pina Concas John M Connell Lisa de Las Fuentes H Janaka de Silva Paul S de Vries Ayo Doumatey Qing Duan Charles B Eaton Ruben N Eppinga Jessica D Faul James S Floyd Nita G Forouhi Terrence Forrester Yechiel Friedlander Ilaria Gandin He Gao Mohsen Ghanbari Sina A Gharib Bruna Gigante Franco Giulianini Hans J Grabe C Charles Gu Tamara B Harris Sami Heikkinen Chew-Kiat Heng Makoto Hirata James E Hixson M Arfan Ikram Yucheng Jia Roby Joehanes Craig Johnson Jost Bruno Jonas Anne E Justice Tomohiro Katsuya Chiea Chuen Khor Tuomas O Kilpeläinen Woon-Puay Koh Ivana Kolcic Charles Kooperberg Jose E Krieger Stephen B Kritchevsky Michiaki Kubo Johanna Kuusisto Timo A Lakka Carl D Langefeld Claudia Langenberg Lenore J Launer Benjamin Lehne Cora E Lewis Yize Li Jingjing Liang Shiow Lin Ching-Ti Liu Jianjun Liu Kiang Liu Marie Loh Kurt K Lohman Tin Louie Anna Luzzi Reedik Mägi Anubha Mahajan Ani W Manichaikul Colin A McKenzie Thomas Meitinger Andres Metspalu Yuri Milaneschi Lili Milani Karen L Mohlke Yukihide Momozawa Andrew P Morris Alison D Murray Mike A Nalls Matthias Nauck Christopher P Nelson Kari E North Jeffrey R O'Connell Nicholette D Palmer George J Papanicolau Nancy L Pedersen Annette Peters Patricia A Peyser Ozren Polasek Neil Poulter Olli T Raitakari Alex P Reiner Frida Renström Treva K Rice Stephen S Rich Jennifer G Robinson Lynda M Rose Frits R Rosendaal Igor Rudan Carsten O Schmidt Pamela J Schreiner William R Scott Peter Sever Yuan Shi Stephen Sidney Mario Sims Jennifer A Smith Harold Snieder John M Starr Konstantin Strauch Heather M Stringham Nicholas Y Q Tan Hua Tang Kent D Taylor Yik Ying Teo Yih Chung Tham Henning Tiemeier Stephen T Turner André G Uitterlinden Diana van Heemst Melanie Waldenberger Heming Wang Lan Wang Lihua Wang Wen Bin Wei Christine A Williams Gregory Wilson Mary K Wojczynski Jie Yao Kristin Young Caizheng Yu Jian-Min Yuan Jie Zhou Alan B Zonderman Diane M Becker Michael Boehnke Donald W Bowden John C Chambers Richard S Cooper Ulf de Faire Ian J Deary Paul Elliott Tõnu Esko Martin Farrall Paul W Franks Barry I Freedman Philippe Froguel Paolo Gasparini Christian Gieger Bernardo L Horta Jyh-Ming Jimmy Juang Yoichiro Kamatani Candace M Kammerer Norihiro Kato Jaspal S Kooner Markku Laakso Cathy C Laurie I-Te Lee Terho Lehtimäki Patrik K E Magnusson Albertine J Oldehinkel Brenda W J H Penninx Alexandre C Pereira Rainer Rauramaa Susan Redline Nilesh J Samani James Scott Xiao-Ou Shu Pim van der Harst Lynne E Wagenknecht Jun-Sing Wang Ya Xing Wang Nicholas J Wareham Hugh Watkins David R Weir Ananda R Wickremasinghe Tangchun Wu Eleftheria Zeggini Wei Zheng Claude Bouchard Michele K Evans Vilmundur Gudnason Sharon L R Kardia Yongmei Liu Bruce M Psaty Paul M Ridker Rob M van Dam Dennis O Mook-Kanamori Myriam Fornage Michael A Province Tanika N Kelly Ervin R Fox Caroline Hayward Cornelia M van Duijn E Shyong Tai Tien Yin Wong Ruth J F Loos Nora Franceschini Jerome I Rotter Xiaofeng Zhu Laura J Bierut W James Gauderman Kenneth Rice Patricia B Munroe Alanna C Morrison Dabeeru C Rao Charles N Rotimi L Adrienne Cupples

Nat Genet 2019 04 29;51(4):636-648. Epub 2019 Mar 29.

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Read More

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http://dx.doi.org/10.1038/s41588-019-0378-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467258PMC
April 2019
8 Reads
29.352 Impact Factor

Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia.

Nat Genet 2019 04 29;51(4):649-658. Epub 2019 Mar 29.

Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.

Late-onset ataxia is common, often idiopathic, and can result from cerebellar, proprioceptive, or vestibular impairment; when in combination, it is also termed cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). We used non-parametric linkage analysis and genome sequencing to identify a biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) gene as the cause of familial CANVAS and a frequent cause of late-onset ataxia, particularly if sensory neuronopathy and bilateral vestibular areflexia coexist. The expansion, which occurs in the poly(A) tail of an AluSx3 element and differs in both size and nucleotide sequence from the reference (AAAAG) allele, does not affect RFC1 expression in patient peripheral and brain tissue, suggesting no overt loss of function. Read More

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http://www.nature.com/articles/s41588-019-0372-4
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http://dx.doi.org/10.1038/s41588-019-0372-4DOI Listing
April 2019
6 Reads

Genomic subtyping and therapeutic targeting of acute erythroleukemia.

Nat Genet 2019 04 29;51(4):694-704. Epub 2019 Mar 29.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Read More

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http://dx.doi.org/10.1038/s41588-019-0375-1DOI Listing
April 2019
1 Read
29.352 Impact Factor

Probabilistic fine-mapping of transcriptome-wide association studies.

Nat Genet 2019 04 29;51(4):675-682. Epub 2019 Mar 29.

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Transcriptome-wide association studies using predicted expression have identified thousands of genes whose locally regulated expression is associated with complex traits and diseases. In this work, we show that linkage disequilibrium induces significant gene-trait associations at non-causal genes as a function of the expression quantitative trait loci weights used in expression prediction. We introduce a probabilistic framework that models correlation among transcriptome-wide association study signals to assign a probability for every gene in the risk region to explain the observed association signal. Read More

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http://dx.doi.org/10.1038/s41588-019-0367-1DOI Listing

Transposable elements drive widespread expression of oncogenes in human cancers.

Nat Genet 2019 04 29;51(4):611-617. Epub 2019 Mar 29.

Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.

Transposable elements (TEs) are an abundant and rich genetic resource of regulatory sequences. Cryptic regulatory elements within TEs can be epigenetically reactivated in cancer to influence oncogenesis in a process termed onco-exaptation. However, the prevalence and impact of TE onco-exaptation events across cancer types are poorly characterized. Read More

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http://dx.doi.org/10.1038/s41588-019-0373-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443099PMC

Opportunities and challenges for transcriptome-wide association studies.

Nat Genet 2019 04 29;51(4):592-599. Epub 2019 Mar 29.

Department of Computer Science, Stanford University, Stanford, CA, USA.

Transcriptome-wide association studies (TWAS) integrate genome-wide association studies (GWAS) and gene expression datasets to identify gene-trait associations. In this Perspective, we explore properties of TWAS as a potential approach to prioritize causal genes at GWAS loci, by using simulations and case studies of literature-curated candidate causal genes for schizophrenia, low-density-lipoprotein cholesterol and Crohn's disease. We explore risk loci where TWAS accurately prioritizes the likely causal gene as well as loci where TWAS prioritizes multiple genes, some likely to be non-causal, owing to sharing of expression quantitative trait loci (eQTL). Read More

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http://dx.doi.org/10.1038/s41588-019-0385-zDOI Listing
April 2019
4 Reads

Genetics for all.

Authors:

Nat Genet 2019 04;51(4):579

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http://dx.doi.org/10.1038/s41588-019-0394-yDOI Listing

Clinical use of current polygenic risk scores may exacerbate health disparities.

Nat Genet 2019 04 29;51(4):584-591. Epub 2019 Mar 29.

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.

Polygenic risk scores (PRS) are poised to improve biomedical outcomes via precision medicine. However, the major ethical and scientific challenge surrounding clinical implementation of PRS is that those available today are several times more accurate in individuals of European ancestry than other ancestries. This disparity is an inescapable consequence of Eurocentric biases in genome-wide association studies, thus highlighting that-unlike clinical biomarkers and prescription drugs, which may individually work better in some populations but do not ubiquitously perform far better in European populations-clinical uses of PRS today would systematically afford greater improvement for European-descent populations. Read More

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http://dx.doi.org/10.1038/s41588-019-0379-xDOI Listing

Expanding the genetic basis of ataxia.

Nat Genet 2019 04;51(4):580-581

Department of Neurology, University of Michigan, Ann Arbor, MI, USA.

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http://dx.doi.org/10.1038/s41588-019-0387-xDOI Listing

Resolving variant-to-function relationships in hematopoiesis.

Nat Genet 2019 04;51(4):581-583

Human Genetics, Wellcome Sanger Institute, Hinxton, UK.

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http://dx.doi.org/10.1038/s41588-019-0386-yDOI Listing

The Effect of Consanguinity on Between-Individual Identity-By-Descent Sharing.

Genetics 2019 Mar 29. Epub 2019 Mar 29.

Stanford University.

Consanguineous unions increase the rate at which identical genomic segments are paired within individuals to produce runs of homozygosity (ROH). The extent to which such unions affect identity-by-descent (IBD) genomic sharing rather than within individuals in a population, however, is not immediately evident from within-individual ROH levels. Using the fact that the time to the most recent common ancestor () for a pair of genomes at a specific locus is inversely related to the extent of IBD sharing between the genomes in the neighborhood of the locus, we study IBD sharing for a pair of genomes sampled either within the same individual or in different individuals. Read More

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http://dx.doi.org/10.1534/genetics.119.302136DOI Listing

The Effects on Neutral Variability of Recurrent Selective Sweeps and Background Selection.

Genetics 2019 Mar 28. Epub 2019 Mar 28.

University of Edinburgh

Levels of variability and rates of adaptive evolution may be affected by hitchhiking, the effect of selection on evolution at linked sites. Hitchhiking can be caused either by selective sweeps or by background selection, involving the spread of new favorable alleles or the elimination of deleterious mutations, respectively. Recent analyses of population genomic data have fitted models where both these processes act simultaneously, in order to infer the parameters of selection. Read More

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http://dx.doi.org/10.1534/genetics.119.301951DOI Listing

Genome-wide association study of four yield-related traits at the R6 stage in soybean.

BMC Genet 2019 Mar 29;20(1):39. Epub 2019 Mar 29.

National Center for Soybean Improvement/National Key laboratory of Crop Genetics and Germplasm enhancement, Key laboratory of Biology and Genetics and Breeding for Soybean, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.

Background: The 100-pod fresh weight (PFW), 100-seed fresh weight (SFW), 100-seed dry weight (SDW) and moisture content of fresh seeds (MCFS) at the R6 stage are crucial factors for vegetable soybean yield. However, the genetic basis of yield at the R6 stage remains largely ambiguous in soybean.

Results: To better understand the molecular mechanism underlying yield, we investigated four yield-related traits of 133 soybean landraces in two consecutive years and conducted a genome-wide association study (GWAS) using 82,187 single nucleotide polymorphisms (SNPs). Read More

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http://dx.doi.org/10.1186/s12863-019-0737-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440021PMC

Clinical metagenomics.

Nat Rev Genet 2019 Mar 27. Epub 2019 Mar 27.

Department of Laboratory Medicine, University of California, San Francisco, CA, USA.

Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health. Read More

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http://dx.doi.org/10.1038/s41576-019-0113-7DOI Listing
March 2019
1 Read

Scanning for determinants of Zika virus host tropism.

Authors:
Dorothy Clyde

Nat Rev Genet 2019 Mar 27. Epub 2019 Mar 27.

Nature Reviews Genetics, .

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http://dx.doi.org/10.1038/s41576-019-0120-8DOI Listing
March 2019
1 Read

Resolving genetic heterogeneity in cancer.

Nat Rev Genet 2019 Mar 27. Epub 2019 Mar 27.

Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, UK.

To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the genetic landscape of most cancer types, and cancer genomics approaches are driving new insights into cancer evolutionary patterns in time and space. In contrast to species evolution, cancer is a particular case owing to the vast size of tumour cell populations, chromosomal instability and its potential for phenotypic plasticity. Read More

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http://dx.doi.org/10.1038/s41576-019-0114-6DOI Listing
March 2019
2 Reads
36.978 Impact Factor

Identification of , a Meiotic Driver Undergoing RNA Editing in Neurospora.

Genetics 2019 Mar 27. Epub 2019 Mar 27.

Illinois State University

is a meiotic drive element that was discovered in wild populations of Neurospora fungi over forty years ago. While early studies quickly determined that transmits itself through sexual reproduction in a biased manner via spore killing, the genetic factors responsible for this phenomenon have remained mostly unknown. Here, we identify and characterize a gene required for -based spore killing. Read More

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http://dx.doi.org/10.1534/genetics.119.302122DOI Listing

CRISPR Gene Drive Efficiency and Resistance Rate Is Highly Heritable with No Common Genetic Loci of Large Effect.

Genetics 2019 Mar 27. Epub 2019 Mar 27.

Cornell University.

Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population over time. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Read More

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http://dx.doi.org/10.1534/genetics.119.302037DOI Listing

Characterization of molecular diversity and genome-wide association study of stripe rust resistance at the adult plant stage in Northern Chinese wheat landraces.

BMC Genet 2019 Mar 26;20(1):38. Epub 2019 Mar 26.

Triticeae Research Institute, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, 611130, People's Republic of China.

Background: Stripe rust is a serious fungal disease of wheat (Triticum aestivum L.) caused by Puccinia striiformis f. sp. Read More

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https://bmcgenet.biomedcentral.com/articles/10.1186/s12863-0
Publisher Site
http://dx.doi.org/10.1186/s12863-019-0736-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434810PMC
March 2019
3 Reads
2.397 Impact Factor

Author Correction: Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis.

Nat Genet 2019 04;51(4):766

Functional Genomics and Metabolism Research Unit, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.

In the version of this article initially published, in the graph keys in Fig. 1i, the colors indicating 'Ob' and 'Ad' were red and blue, respectively, but should have been blue and red, respectively; the shapes indicating 'MUS' and 'BM' were a triangle and a square, respectively, but should have been a square and a triangle, respectively. The errors have been corrected in the HTML and PDF versions of the article. Read More

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http://dx.doi.org/10.1038/s41588-019-0400-4DOI Listing

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk.

Nat Genet 2019 04 25;51(4):659-674. Epub 2019 Mar 25.

Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. Read More

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http://dx.doi.org/10.1038/s41588-019-0364-4DOI Listing
April 2019
1 Read
29.352 Impact Factor

Optimizing biological inferences from single-cell data.

Authors:

Nat Rev Genet 2019 May;20(5):249

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http://dx.doi.org/10.1038/s41576-019-0118-2DOI Listing
May 2019
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Repression of Germline Genes in Somatic Tissues by H3K9 Dimethylation of Their Promoters.

Genetics 2019 Mar 25. Epub 2019 Mar 25.

Marquette University

Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three synMuv B mutants, and , all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. Read More

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http://dx.doi.org/10.1534/genetics.118.301878DOI Listing

Karyotypic and mtDNA based characterization of Malaysian water buffalo.

BMC Genet 2019 Mar 25;20(1):37. Epub 2019 Mar 25.

Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Malaysia.

Background: In Malaysia, the domestic water buffaloes (Bubalus bubalis) are classified into the swamp and the murrah buffaloes. Identification of these buffaloes is usually made via their phenotypic appearances. This study characterizes the subspecies of water buffaloes using karyotype, molecular and phylogenetic analyses. Read More

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http://dx.doi.org/10.1186/s12863-019-0741-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434848PMC

Differences in Effective Ploidy Drive Genome-Wide Endosperm Expression Polarization and Seed Failure in Wild Tomato Hybrids.

Genetics 2019 Mar 22. Epub 2019 Mar 22.

ETH Zurich

Parental imbalances in the endosperm leading to impaired development and eventual hybrid seed failure are common causes of postzygotic isolation in flowering plants. Endosperm sensitivity to parental dosage is reflected by canonical phenotypes of 'parental excess' in reciprocal interploid crosses. Moreover, parental-excess traits are also evident in many homoploid interspecific crosses, potentially reflecting among-lineage variation in 'effective ploidy' driven by endosperm properties. Read More

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http://dx.doi.org/10.1534/genetics.119.302056DOI Listing