Nature Genetics Contents: August 2016 pp 821 - 970

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Get more information at http://www.eppendorf.com/physiocare TABLE OF CONTENTS August 2016 Volume 48, Issue 8 Editorial News and Views Analysis Articles Letters Technical Report Erratum Corrigenda Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Medicine and the Volkswagen Foundation present:  GENOME EDITING FOR GENE AND CELL THERAPY, A HERRENHAUSEN SYMPOSIUM November 3-4, 2016 | Herrenhausen Palace Conference Center, Hanover, Germany REGISTER NOW!   Advertisement Benefits of publishing in Human Genome Variation (HGV) - Quality peer-review and fast decision times - Research Summaries to enhance the reach of your work - High visibility for your research  Submit your research today and contribute to this exciting journal!   Editorial Top European Open Science Cloud   p821 doi:10.1038/ng.3642 A recent recommendation that a large number of professional data stewards be trained and employed in all data-rich research projects raises the exciting prospect they will conduct research on data-intensive research itself. It also focuses us on questions about the role of all scientists in data quality and accessibility as well as how best to measure the value of good data stewardship to science and society. News and Views Top Poised for development   pp822 - 823 Lauren A Choate and Charles G Danko doi:10.1038/ng.3628 A new study tracks the distribution of bivalent H3K4me3/H3K27me3 chromatin in male germ cells of six vertebrate species. The results have big implications for understanding the mechanisms that specify animal development. See also: Article by Lesch et al. Decoding germline de novo point mutations   pp823 - 824 Anne Goriely doi:10.1038/ng.3629 Analysis of a large whole-genome sequencing data set of 36,441 high-quality de novo mutations (DNMs) that arose in 816 family trios provides an unprecedented view into the landscape of DNMs in the germ line. This work both refines and challenges some of the views previously held on the nature and origin of DNMs. See also: Letter by Goldmann et al. An unsettling picture emerges from population genomic studies of Plasmodium vivax   pp825 - 826 Jessica C Kissinger doi:10.1038/ng.3630 Two new studies confirm that Plasmodium vivax populations are more diverse than Plasmodium falciparum and identify signs of recent selection at many loci, including those for drug resistance. P. vivax shows a trend of regional adaptations that poses challenges to global efforts to control and eliminate this major cause of relapsing malaria. See also: Letter by Hupalo et al. | Letter by Pearson et al. Genetics JOBS of the week Head Scientist in Mosquito Ecology and Genetics Polo d'Innovazione Genomica Genetica e Biologia SCaRL W2-Professorship in Genetics Friedrich Schiller University Jena Postdoctoral Fellow - Malaria Genetics Wellcome Trust Sanger Institute Research Assistant Professor in Computational Genomics and Genetics of Alzheimer’s Disease University of Pennsylvania Experimental Postdoc Position: Single-cell Functional Genomics Center for Molecular Biology (ZMBH), Heidelberg University More Science jobs from Genetics EVENT World Congress of Psychiatric Genetics 30th Oct - 3rd Nov 2016 Jerusalem, Israel More science events from Analysis Top Protein-structure-guided discovery of functional mutations across 19 cancer types   pp827 - 837 Beifang Niu, Adam D Scott, Sohini Sengupta, Matthew H Bailey, Prag Batra et al. doi:10.1038/ng.3586 Li Ding, Feng Chen and colleagues report a pan-cancer analysis using a new computational tool, HotSpot3D, to identify mutational hotspots in the encoded three-dimensional protein structure, which suggest their functional involvement in cancer. They use a mutation-drug cluster analysis to predict more than 800 potentially druggable mutations. Functional characterization of somatic mutations in cancer using network-based inference of protein activity   pp838 - 847 Mariano J Alvarez, Yao Shen, Federico M Giorgi, Alexander Lachmann, B Belinda Ding et al. doi:10.1038/ng.3593 Andrea Califano, Mariano Alvarez and colleagues present an approach, VIPER, for inferring protein activity in single cancer samples based on expression of a protein's downstream targets. The authors use VIPER to predict aberrant protein activity independent of mutational status and validate drug sensitivity predictions using in vitro assays. Articles Top The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis   pp848 - 855 William J Gibson, Erling A Hoivik, Mari K Halle, Amaro Taylor-Weiner, Andrew D Cherniack et al. doi:10.1038/ng.3602 Helga Salvesen, Rameen Beroukhim, Scott Carter and colleagues study the evolutionary landscape of endometrial cancer by performing whole-exome sequencing of complex atypical hyperplasias, primary tumors and metastases. They identify recurrent alterations in primary tumors and suggest that driver events are generally shared by primary and metastatic tumors. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine   pp856 - 866 Padhraig Gormley, Verneri Anttila, Bendik S Winsvold, Priit Palta, Tonu Esko et al. doi:10.1038/ng.3598 Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues. Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits   pp867 - 876 Nathan Pankratz, Ursula M Schick, Yi Zhou, Wei Zhou, Tarunveer Singh Ahluwalia et al. doi:10.1038/ng.3607 Nathan Pankratz, Santhi Ganesh and colleagues use exome chip data to identify rare and common variants influencing blood cell traits. They report associations at several loci, including a rare missense variant in S1PR4 associated with circulating neutrophil counts, and present functional studies supporting a role for S1PR4 in neutrophil recruitment and resolution in response to tissue injury. Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity   pp877 - 887 Josefine S Witteveen, Marjolein H Willemsen, Thaís C D Dombroski, Nick H M van Bakel, Willy M Nillesen et al. doi:10.1038/ng.3619 Sharon Kolk, Tjitske Kleefstra and colleagues identify loss-of-function mutations in SIN3A in individuals with intellectual disability and other clinical features. They further show that knockdown of Sin3a in developing mouse brain results in reduced cortical neurogenesis, altered neuronal identity and aberrant cortical projections, identifying this MeCP2-interacting protein as a key regulator of cortical development. Parallel evolution of male germline epigenetic poising and somatic development in animals   pp888 - 894 Bluma J Lesch, Sherman J Silber, John R McCarrey and David C Page doi:10.1038/ng.3591 David Page and colleagues examine genes with bivalent chromatin modifications in male germ cells from five mammalian species and chicken. They find that the set of bivalently marked genes shared by all species represent evolutionarily ancient morphogenesis regulators, whereas genes showing lineage-specific bivalent marks act downstream of these core regulators. See also: News and Views by Choate & Danko Genetic dissection of the α-globin super-enhancer in vivo   pp895 - 903 Deborah Hay, Jim R Hughes, Christian Babbs, James O J Davies, Bryony J Graham et al. doi:10.1038/ng.3605 Douglas Higgs and colleagues functionally test the α-globin super-enhancer in mice by genetically deleting its constituent enhancers. They find that the individual regulatory elements seem to act independently and in an additive way with respect to hematological phenotype, gene expression, and chromatin structure and conformation. Hierarchy within the mammary STAT5-driven Wap super-enhancer   pp904 - 911 Ha Youn Shin, Michaela Willi, Kyung Hyun Yoo, Xianke Zeng, Chaochen Wang et al. doi:10.1038/ng.3606 Lothar Hennighausen and colleagues identify 440 mammary-specific super-enhancers in mouse and focus on the STAT5-regulated Wap gene. Genetic dissection of the Wap super-enhancer suggests an internal hierarchy, as mutations in one of the constituent enhancers incapacitate the entire regulatory region. Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing   pp912 - 918 Jérôme Nicod, Robert W Davies, Na Cai, Carl Hassett, Leo Goodstadt et al. doi:10.1038/ng.3595 Jonathan Flint, Richard Mott and colleagues employ low-coverage (0.15×) sequencing and their new imputation method STITCH to perform genome-wide association analysis for complex traits in an outbred mouse population. They find >250 QTLs for 92 phenotypes and obtain gene-level mapping resolution for around 20% of the loci. Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice   pp919 - 926 Clarissa C Parker, Shyam Gopalakrishnan, Peter Carbonetto, Natalia M Gonzales, Emily Leung et al. doi:10.1038/ng.3609 Abraham Palmer and colleagues use genotyping by sequencing to perform genome-wide association studies on CFW mice for behavioral, physiological and gene expression traits. They find many QTLs and incorporate expression QTL analysis to prioritize specific genes at loci of interest that underlie different complex traits. Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice   pp927 - 934 Kenji Yano, Eiji Yamamoto, Koichiro Aya, Hideyuki Takeuchi, Pei-ching Lo et al. doi:10.1038/ng.3596 Makoto Matsuoka and colleagues use a whole-genome sequencing-based approach to perform genome-wide association analysis for important agronomic traits in rice. Using phenotypically diverse rice with low interrelationships, they rapidly identify novel genes associated with heading date, plant height and panicle number per plant, validating candidates with transgenic experiments. Advertisement npj Molecular Phenomics is a new open access journal that is now open for submissions. The journal encourages studies that integrate diverse phenotyping approaches to understand the molecular aspects of phenomes. Sign up for e-alerts   Letters Top Parent-of-origin-specific signatures of de novo mutations   pp935 - 939 Jakob M Goldmann, Wendy S W Wong, Michele Pinelli, Terry Farrah, Dale Bodian et al. doi:10.1038/ng.3597 Christian Gilissen, John Niederhuber and colleagues examine de novo mutations with parent-of-origin information from whole-genome sequencing datasets from 816 parent-offspring trios. They find maternal and paternal specific mutation signatures that are more prominent with increased age of the parent as well as clustered mutation signatures with no parental bias. See also: News and Views by Goriely Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus   pp940 - 946 David L Morris, Yujun Sheng, Yan Zhang, Yong-Fei Wang, Zhengwei Zhu et al. doi:10.1038/ng.3603 Timothy Vyse, Yong Cui, Wanling Yang and colleagues report a meta-analysis of genome-wide association studies for systemic lupus erythematosus (SLE) including European and Chinese individuals. They identify ten new loci associated with SLE and find evidence for increased genetic risk of disease among individuals of non-European ancestry. Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation OPEN   pp947 - 952 Li Yu, Guo-Dong Wang, Jue Ruan, Yong-Bin Chen, Cui-Ping Yang et al. doi:10.1038/ng.3615 Li Yu, Ya-Ping Zhang, Chung-I Wu and colleagues report the de novo genome of the black snub-nosed monkey Rhinopithecus bieti and the genomic sequences of four other Rhinopithecus species, including three high-altitude and two lowland species. The species- and population-level genomic analyses as well as the transcriptomic analysis and functional assays find adaptive signatures associated with adaptation to high altitude. Population genomics studies identify signatures of global dispersal and drug resistance in Plasmodium vivax   pp953 - 958 Daniel N Hupalo, Zunping Luo, Alexandre Melnikov, Patrick L Sutton, Peter Rogov et al. doi:10.1038/ng.3588 Jane Carlton, Daniel Neafsey and colleagues report a population genomics analysis of 182 Plasmodium vivax isolates from 11 countries. They find evidence of regional adaptation and signatures of selection at genes involved in antimalarial drug resistance. See also: News and Views by Kissinger | Letter by Pearson et al. Genomic analysis of local variation and recent evolution in Plasmodium vivax   pp959 - 964 Richard D Pearson, Roberto Amato, Sarah Auburn, Olivo Miotto, Jacob Almagro-Garcia et al. doi:10.1038/ng.3599 Dominic Kwiatkowski and colleagues report a population genomic analysis of 228 clinical samples of Plasmodium vivax from 13 countries, with an emphasis on Southeast Asia. They analyze patterns of genetic structure within individual infections and find evidence for regional adaptation at the population level. See also: News and Views by Kissinger | Letter by Hupalo et al. Technical Report Top Rapid genotype imputation from sequence without reference panels   pp965 - 969 Robert W Davies, Jonathan Flint, Simon Myers and Richard Mott doi:10.1038/ng.3594 Richard Mott, Simon Myers and colleagues present a new imputation method, STITCH, which does not require genotyping arrays or high-quality reference panels. They use STITCH to accurately impute genotypes in both outbred laboratory mice and a sample human population directly from low-coverage (<2×) sequencing data. Erratum Top Erratum: Cis-regulatory architecture of a brain signaling center predates the origin of chordates   p970 Yao Yao, Paul J Minor, Ying-Tao Zhao, Yongsu Jeong, Ariel M Pani et al. doi:10.1038/ng0816-970a Corrigenda Top Corrigendum: The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery   p970 Michinori Toriyama, Chanjae Lee, S Paige Taylor, Ivan Duran, Daniel H Cohn et al. doi:10.1038/ng0816-970b Corrigendum: Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses   p970 Aysu Okbay, Bart M L Baselmans, Jan-Emmanuel De Neve, Patrick Turley, Michel G Nivard et al. doi:10.1038/ng0816-970c Top Advertisement Celebrating 10,000 articles published On the 20th April 2016, Nature Communications celebrated publishing its 10,000 article. 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