Nature Genetics Contents: March 2018 Volume 50 Number 3

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Advertisement For the first time, scientists have sequenced the entire MHC locus, fully-phased. How? Cas9- selected HMW targets with SageHLS (HLS-CATCH). Learn More. TABLE OF CONTENTS March 2018 Volume 50, Issue 3 Editorial News & Views Perspectives Brief Communications Letters Articles   Advertisement   This Survival Guide Will Save the Genetic Integrity of Your Breeding Colony With a direct impact on the quality of your preclinical research, a robust genetic monitoring system of breeding stock, genetic drift, and strain variations can save almost any research program. Learn what steps you can take to verify the genetic backgrounds of your breeding stock.  Watch Now!   Advertisement Curating the Clinical Genome (23-25 May 2018)  This conference will bring together the clinical genomics community to discuss best practices for the clinical use of genomic data, including interpretation and clinical utility, and the consensus generation of curated knowledge. Deadlines: Early bird: 27 Feb/ Bursaries: 13 Mar/ Abstracts: 27 Mar / Registration: 24 Apr   Advertisement Naturejobs Career Guide China 2018  China's scientific landscape is shifting fast. Where can you fit in? Read the latest issue of our career guide to see what opportunities await you.  Read more online >>    Advertisement Animation on CRISPR: Gene editing and beyond  The CRISPR-Cas9 system has revolutionised gene editing, but cutting DNA isn't all it can do. This Animation, from Nature Methods, explores where CRISPR might be headed next.  Watch the Animation >>  Produced with support from:  Dharmacon    Editorial   Genetics for your whole life    p317 doi:10.1038/s41588-018-0072-5 News & Views   Eggs sense high-fat diet    pp318 - 319 Harry G. Leitch & Petra Hajkova doi:10.1038/s41588-018-0068-1 Elucidating the genetics of craniofacial shape    pp319 - 321 David M. Evans doi:10.1038/s41588-018-0065-4 Genetics JOBS of the week Postdoctoral Research Fellow Kovler Diabetes Center at the University of Chicago Post-doctoral Fellow Stanford University - School of Medicine Postdoctoral Fellow Opportunity – Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory (CSHL) Associate Research Scientist Columbia University Research group leader (2 positions) Centre of New Technologies, University of Warsaw More Science jobs from Genetics EVENT Genes, Brain, and Behavior Meeting 2018 21.05.18 Rochester, USA More science events from Perspectives   The importance of cohort studies in the post-GWAS era    pp322 - 328 Cisca Wijmenga & Alexandra Zhernakova doi:10.1038/s41588-018-0066-3 This Perspective describes different study designs for the genetic analyses of large-scale cohorts, using Dutch cohorts as primary examples, and discusses lessons learned as well as recommendations for future cohort studies.   Brief Communications   BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome    pp329 - 332 Gabrielle Olley, Morad Ansari, Hemant Bengani, Graeme R. Grimes, James Rhodes et al. doi:10.1038/s41588-018-0042-y The clinical phenotype associated with BRD4 haploinsufficiency overlaps with Cornelia de Lange syndrome, which is often caused by mutations in NIPBL. The authors show that BRD4 and NIPBL physically interact and co-bind at super-enhancers.   Letters   The human noncoding genome defined by genetic diversity    pp333 - 337 Julia di Iulio, Istvan Bartha, Emily H. M. Wong, Hung-Chun Yu, Victor Lavrenko et al. doi:10.1038/s41588-018-0062-7 This study presents a map of sequence constraint in humans based on 11,257 whole-genome sequences and 16,384 heptamers. The map identifies regulatory elements among the most constrained regions of the genome and will aid interpretation of noncoding variants.   Exome-wide analyses identify low-frequency variant in CYP26B1 and additional coding variants associated with esophageal squamous cell carcinoma    pp338 - 343 Jiang Chang, Rong Zhong, Jianbo Tian, Jiaoyuan Li, Kan Zhai et al. doi:10.1038/s41588-018-0045-8 Exome-wide analyses identify low-frequency coding variants associated with esophageal squamous cell carcinoma. One of the risk variants, in CYP26B1, is associated with enhanced enzymatic activity and lower levels of all-trans retinoic acid in serum.   Human TGF-ß1 deficiency causes severe inflammatory bowel disease and encephalopathy    pp344 - 348 Daniel Kotlarz, Benjamin Marquardt, Tuva Barøy, Way S. Lee, Liza Konnikova et al. doi:10.1038/s41588-018-0063-6 Biallelic loss-of-function mutations in TGFB1 are reported in three individuals with severe infantile inflammatory bowel disease and neurodevelopmental delay. These findings highlight a critical role for TGF-ß1 in human intestinal homeostasis and central nervous system development.   CLCN2 chloride channel mutations in familial hyperaldosteronism type II    pp349 - 354 Ute I. Scholl, Gabriel Stölting, Julia Schewe, Anne Thiel, Hua Tan et al. doi:10.1038/s41588-018-0048-5 Whole-exome sequencing identifies mutations in CLCN2 in individuals with familial hyperaldosteronism type II or early-onset primary aldosteronism. These gain-of-function mutations cause chloride channel opening and glomerulosa cell depolarization, showing a role for anion channels in aldosterone production.   A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism    pp355 - 361 Fabio L. Fernandes-Rosa, Georgios Daniil, Ian J. Orozco, Corinna Göppner, Rami El Zein et al. doi:10.1038/s41588-018-0053-8 A gain-of-function mutation in the CLCN2 chloride channel gene (encoding ClC-2) causes primary aldosteronism. The mutation abolishes voltage-dependent gating of ClC-2, highlighting a role for chloride conduction in regulating aldosterone biosynthesis.   Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals    pp362 - 367 Aniek C. Bouwman, Hans D. Daetwyler, Amanda J. Chamberlain, Carla Hurtado Ponce, Mehdi Sargolzaei et al. doi:10.1038/s41588-018-0056-5 Meta-analysis of data from 58,265 cattle shows that the genetic architecture underlying stature is similar to that in humans, where many genomic regions individually explain only a small amount of phenotypic variance.   Wheat receptor-kinase-like protein Stb6 controls gene-for-gene resistance to fungal pathogen Zymoseptoria tritici    pp368 - 374 Cyrille Saintenac, Wing-Sham Lee, Florence Cambon, Jason J. Rudd, Robert C. King et al. doi:10.1038/s41588-018-0051-x The authors report map-based cloning of the wheat Stb6 gene, which encodes a conserved wall-associated receptor kinase (WAK)-like protein. Stb6 confers gene-for-gene disease resistance to fungal pathogen Zymoseptoria tritici by recognition of a matching pathogen effector.   Stress and sexual reproduction affect the dynamics of the wheat pathogen effector AvrStb6 and strobilurin resistance    pp375 - 380 Gerrit H. J. Kema, Amir Mirzadi Gohari, Lamia Aouini, Hesham A. Y. Gibriel, Sarah B. Ware et al. doi:10.1038/s41588-018-0052-9 Identification of AvrStb6, the fungal avirulence effector that triggers Stb6-mediated resistance in wheat, here demonstrates that neither host resistance nor fungicide treatment suppresses fungal sexual reproduction, thus unveiling implications of fungal sex in plant disease control.   Advertisement Do you have a career question?  The Naturejobs podcast features one-on-one Q&As, panel discussions and other exclusive content to help scientists with their careers. Hosted on the Naturejobs blog, the podcast is also available on iTunes and Soundcloud.  Listen today!   Articles   Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection    pp381 - 389 Antonio F. Pardiñas, Peter Holmans, Andrew J. Pocklington, Valentina Escott-Price, Stephan Ripke et al. doi:10.1038/s41588-018-0059-2 A new GWAS of schizophrenia (11,260 cases and 24,542 controls) and meta-analysis identifies 50 new associated loci and 145 loci in total. The common variant association signal is highly enriched in mutation-intolerant genes and in regions under strong background selection.   Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases    pp390 - 400 Masahiro Kanai, Masato Akiyama, Atsushi Takahashi, Nana Matoba, Yukihide Momozawa et al. doi:10.1038/s41588-018-0047-6 A genome-wide association study (GWAS) of 58 traits using data from the Biobank Japan Project identifies 1,407 loci, 679 of which are novel. Comparison with disease GWASs and analysis of genetic correlations and cell-type enrichment show that these clinical measurements are relevant to human disease.   A large electronic-health-record-based genome-wide study of serum lipids    pp401 - 413 Thomas J. Hoffmann, Elizabeth Theusch, Tanushree Haldar, Dilrini K. Ranatunga, Eric Jorgenson et al. doi:10.1038/s41588-018-0064-5 Genome-wide association analysis using electronic health record data from >94,000 individuals identifies loci associated with plasma lipid concentrations. Longitudinal measurements allow for the calculation of genetic risk scores and increase the variance explained.   Genome-wide mapping of global-to-local genetic effects on human facial shape    pp414 - 423 Peter Claes, Jasmien Roosenboom, Julie D. White, Tomek Swigut, Dzemila Sero et al. doi:10.1038/s41588-018-0057-4 The authors report a data-driven approach to phenotyping 3D facial shape. They apply their methodology to 2,329 individuals of European ancestry and identify 38 loci that associate with specific facial morphologies, some of which overlap with neural-crest-specific regulatory regions.   Shared genetic effects on chromatin and gene expression indicate a role for enhancer priming in immune response    pp424 - 431 Kaur Alasoo, Julia Rodrigues, Subhankar Mukhopadhyay, Andrew J. Knights, Alice L. Mann et al. doi:10.1038/s41588-018-0046-7 Analysis of chromatin accessibility and expression quantitative trait loci in stimulated or naïve macrophages identifies loci that constitutively alter chromatin but affect expression only after stimulation, thus indicating an effect on enhancer priming.   Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes    pp432 - 442 Longsen Han, Chao Ren, Ling Li, Xiaoyan Li, Juan Ge et al. doi:10.1038/s41588-018-0055-6 The authors find that, in a high-fat diet (HFD) mouse model, levels of Stella protein are reduced in oocytes, leading to abnormal epigenetic patterning during development and to embryonic growth defects. Overexpression of Stella in oocytes from HFD-fed mice partially ameliorates developmental defects.   RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells    pp443 - 451 Diana Guallar, Xianju Bi, Jose Angel Pardavila, Xin Huang, Carmen Saenz et al. doi:10.1038/s41588-018-0060-9 The authors show that TET2 is recruited to chromatin by the RNA-binding protein PSPC1. PSPC1 and TET2 contribute to ERV and ERV-associated gene regulation by both transcriptional repression via histone deacetylases and post-transcriptional destabilization of ERV RNAs through 5hmC modification.   Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity    pp452 - 459 Silvana Rošic, Rachel Amouroux, Cristina E. Requena, Ana Gomes, Max Emperle et al. doi:10.1038/s41588-018-0061-8 The authors report that DNA methylation coevolves with the DNA alkylation repair enzyme ALKB2 across eukaryotes. They also show that DNA methyltransferases cause alkylation damage in vitro and in vivo by introducing 3-methylcytosine into DNA.   A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies    pp460 - 471 David K. Breslow, Sascha Hoogendoorn, Adam R. Kopp, David W. Morgens, Brandon K. Vu et al. doi:10.1038/s41588-018-0054-7 A CRISPR-based functional screen for Hedgehog-pathway factors identifies genes required for ciliary signaling and can be used to classify genetic disorders as ciliopathies.   Advertisement Nature Collection: 2017 Nobel Prize in Physiology or Medicine The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their pioneering work in Drosophila that elucidated the molecular mechanisms controlling circadian rhythm.  Access this collection free online>> Produced with support from:  Vanda Pharmaceuticals     Advertisement Nature Mentoring Collection  Offering advice and support to scientist mentors and their mentees  Access the Collection >>    Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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