Volume 49 Issue 11, 1 November 2017

Article

  • Article |

    Danielle Posthuma and colleagues report a genome-wide association analysis for insomnia complaints in 113,006 individuals from the UK Biobank that identifies associations with variants near seven genes. They find evidence for sex-specific genetic architectures underlying genetic risk for insomnia and genetic correlations between insomnia complaints and psychiatric and metabolic traits.

    • Anke R Hammerschlag
    • , Sven Stringer
    • , Christiaan A de Leeuw
    • , Suzanne Sniekers
    • , Erdogan Taskesen
    • , Kyoko Watanabe
    • , Tessa F Blanken
    • , Kim Dekker
    • , Bart H W te Lindert
    • , Rick Wassing
    • , Ingileif Jonsdottir
    • , Gudmar Thorleifsson
    • , Hreinn Stefansson
    • , Thorarinn Gislason
    • , Klaus Berger
    • , Barbara Schormair
    • , Juergen Wellmann
    • , Juliane Winkelmann
    • , Kari Stefansson
    • , Konrad Oexle
    • , Eus J W Van Someren
    •  & Danielle Posthuma
  • Article |

    Lineage-tracing experiments in the mouse show that Lgr6, but not Lgr5, functions as a cancer stem marker in skin squamous cell carcinomas (SCCs). The authors also show that Lgr6-knockout mice are predisposed to SCC development, through a mechanism that includes compensatory upregulation of Lgr5.

    • Phillips Y Huang
    • , Eve Kandyba
    • , Arnaud Jabouille
    • , Jonas Sjolund
    • , Atul Kumar
    • , Kyle Halliwill
    • , Melissa McCreery
    • , Reyno DelRosario
    • , Hio Chung Kang
    • , Christine E Wong
    • , Jost Seibler
    • , Vincent Beuger
    • , Maurizio Pellegrino
    • , Adam Sciambi
    • , Dennis J Eastburn
    •  & Allan Balmain
  • Article |

    Loss of BAF47 destabilizes the BAF complex on chromatin, and reintroduction of BAF47 leads to enhancer activation and Polycomb opposition at bivalent promoters. BAF47 loss affects BAF and PBAF complexes, which have distinct functions in regulation of enhancers and promoters.

    • Robert T Nakayama
    • , John L Pulice
    • , Alfredo M Valencia
    • , Matthew J McBride
    • , Zachary M McKenzie
    • , Mark A Gillespie
    • , Wai Lim Ku
    • , Mingxiang Teng
    • , Kairong Cui
    • , Robert T Williams
    • , Seth H Cassel
    • , He Qing
    • , Christian J Widmer
    • , George D Demetri
    • , Rafael A Irizarry
    • , Keji Zhao
    • , Jeffrey A Ranish
    •  & Cigall Kadoch
  • Article |

    High-resolution contact maps of active enhancers and target genes generated by H3K27ac HiChIP in primary human cells provide rational guides to link noncoding disease-associated risk variants to candidate causal genes. Genes are validated by CRISPR activation and interference at connected enhancers and eQTL analysis, leading to a fourfold increase in the number of potential target genes for autoimmune and cardiovascular diseases.

    • Maxwell R Mumbach
    • , Ansuman T Satpathy
    • , Evan A Boyle
    • , Chao Dai
    • , Benjamin G Gowen
    • , Seung Woo Cho
    • , Michelle L Nguyen
    • , Adam J Rubin
    • , Jeffrey M Granja
    • , Katelynn R Kazane
    • , Yuning Wei
    • , Trieu Nguyen
    • , Peyton G Greenside
    • , M Ryan Corces
    • , Josh Tycko
    • , Dimitre R Simeonov
    • , Nabeela Suliman
    • , Rui Li
    • , Jin Xu
    • , Ryan A Flynn
    • , Anshul Kundaje
    • , Paul A Khavari
    • , Alexander Marson
    • , Jacob E Corn
    • , Thomas Quertermous
    • , William J Greenleaf
    •  & Howard Y Chang

    Collection:

  • Article |

    Exome sequencing of 2,871 probands with congenital heart disease (CHD) provides new insights into the genetic architecture of these disorders. The results implicate new genes in CHD pathogenesis and highlight striking overlap between genes with damaging de novo mutations in individuals with CHD and autism.

    • Sheng Chih Jin
    • , Jason Homsy
    • , Samir Zaidi
    • , Qiongshi Lu
    • , Sarah Morton
    • , Steven R DePalma
    • , Xue Zeng
    • , Hongjian Qi
    • , Weni Chang
    • , Michael C Sierant
    • , Wei-Chien Hung
    • , Shozeb Haider
    • , Junhui Zhang
    • , James Knight
    • , Robert D Bjornson
    • , Christopher Castaldi
    • , Irina R Tikhonoa
    • , Kaya Bilguvar
    • , Shrikant M Mane
    • , Stephan J Sanders
    • , Seema Mital
    • , Mark W Russell
    • , J William Gaynor
    • , John Deanfield
    • , Alessandro Giardini
    • , George A Porter Jr
    • , Deepak Srivastava
    • , Cecelia W Lo
    • , Yufeng Shen
    • , W Scott Watkins
    • , Mark Yandell
    • , H Joseph Yost
    • , Martin Tristani-Firouzi
    • , Jane W Newburger
    • , Amy E Roberts
    • , Richard Kim
    • , Hongyu Zhao
    • , Jonathan R Kaltman
    • , Elizabeth Goldmuntz
    • , Wendy K Chung
    • , Jonathan G Seidman
    • , Bruce D Gelb
    • , Christine E Seidman
    • , Richard P Lifton
    •  & Martina Brueckner
  • Article | | open

    The assembly of the durian genome provides insights into the unique flavor profile of this tropical fruit. Transcriptome and metabolome analyses show that methionine γ-lyase is upregulated and that volatile sulfur compounds are produced during ripening.

    • Bin Tean Teh
    • , Kevin Lim
    • , Chern Han Yong
    • , Cedric Chuan Young Ng
    • , Sushma Ramesh Rao
    • , Vikneswari Rajasegaran
    • , Weng Khong Lim
    • , Choon Kiat Ong
    • , Ki Chan
    • , Vincent Kin Yuen Cheng
    • , Poh Sheng Soh
    • , Sanjay Swarup
    • , Steven G Rozen
    • , Niranjan Nagarajan
    •  & Patrick Tan
  • Article |

    A genome-wide association analysis using data from Chinese individuals combined with a transethnic meta-analysis of Psychiatry Genomics Consortium data identifies 30 new loci for schizophrenia. These analyses improve the fine-mapping of susceptibility loci and implicate multiple pathways in schizophrenia biology.

    • Zhiqiang Li
    • , Jianhua Chen
    • , Hao Yu
    • , Lin He
    • , Yifeng Xu
    • , Dai Zhang
    • , Qizhong Yi
    • , Changgui Li
    • , Xingwang Li
    • , Jiawei Shen
    • , Zhijian Song
    • , Weidong Ji
    • , Meng Wang
    • , Juan Zhou
    • , Boyu Chen
    • , Yahui Liu
    • , Jiqiang Wang
    • , Peng Wang
    • , Ping Yang
    • , Qingzhong Wang
    • , Guoyin Feng
    • , Benxiu Liu
    • , Wensheng Sun
    • , Baojie Li
    • , Guang He
    • , Weidong Li
    • , Chunling Wan
    • , Qi Xu
    • , Wenjin Li
    • , Zujia Wen
    • , Ke Liu
    • , Fang Huang
    • , Jue Ji
    • , Stephan Ripke
    • , Weihua Yue
    • , Patrick F Sullivan
    • , Michael C O'Donovan
    •  & Yongyong Shi

Letter

  • Letter |

    Missense mutations affecting lysine 91 in the histone H4 core cause a developmental syndrome marked by growth delay, microcephaly and intellectual disability. These mutations cause genomic instability by interfering with H4K91 ubiquitination, leading to abnormal cell cycle progression and apoptosis during early development.

    • Federico Tessadori
    • , Jacques C Giltay
    • , Jane A Hurst
    • , Maarten P Massink
    • , Karen Duran
    • , Harmjan R Vos
    • , Robert M van Es
    • , Deciphering Developmental Disorders Study
    • , Richard H Scott
    • , Koen L I van Gassen
    • , Jeroen Bakkers
    •  & Gijs van Haaften
  • Letter |

    Ali Shilatifard and colleagues generate Drosophila lines expressing catalytically deficient Trr, which normally deposits H3K4me1 at enhancers. Trr mutants undergo normal development and show minimal changes in gene expression.

    • Ryan Rickels
    • , Hans-Martin Herz
    • , Christie C Sze
    • , Kaixiang Cao
    • , Marc A Morgan
    • , Clayton K Collings
    • , Maria Gause
    • , Yoh-hei Takahashi
    • , Lu Wang
    • , Emily J Rendleman
    • , Stacy A Marshall
    • , Annika Krueger
    • , Elizabeth T Bartom
    • , Andrea Piunti
    • , Edwin R Smith
    • , Nebiyu A Abshiru
    • , Neil L Kelleher
    • , Dale Dorsett
    •  & Ali Shilatifard

Technical Report

  • Technical Report |

    Graphtyper is a fast and scalable method for variant genotyping that aligns short-read sequence data to a pangenome. Graphtyper was able to accurately genotype 90 million sequence variants in the whole genomes of 28,000 Icelanders, including those in six HLA genes.

    • Hannes P Eggertsson
    • , Hakon Jonsson
    • , Snaedis Kristmundsdottir
    • , Eirikur Hjartarson
    • , Birte Kehr
    • , Gisli Masson
    • , Florian Zink
    • , Kristjan E Hjorleifsson
    • , Aslaug Jonasdottir
    • , Adalbjorg Jonasdottir
    • , Ingileif Jonsdottir
    • , Daniel F Gudbjartsson
    • , Pall Melsted
    • , Kari Stefansson
    •  & Bjarni V Halldorsson

Analysis

  • Analysis |

    This large-scale analysis of copy number alterations (CNAs) in patient-derived xenografts (PDXs) across 24 cancer types shows that new CNAs accumulate quickly and that the specific CNAs acquired during passaging differ from those acquired during tumor evolution in patients, suggesting that PDX tumors are under distinct selection pressures from tumors in human hosts.

    • Uri Ben-David
    • , Gavin Ha
    • , Yuen-Yi Tseng
    • , Noah F Greenwald
    • , Coyin Oh
    • , Juliann Shih
    • , James M McFarland
    • , Bang Wong
    • , Jesse S Boehm
    • , Rameen Beroukhim
    •  & Todd R Golub

Commentary

  • Commentary |

    • Jennifer A Brody
    • , Alanna C Morrison
    • , Joshua C Bis
    • , Jeffrey R O'Connell
    • , Michael R Brown
    • , Jennifer E Huffman
    • , Darren C Ames
    • , Andrew Carroll
    • , Matthew P Conomos
    • , Stacey Gabriel
    • , Richard A Gibbs
    • , Stephanie M Gogarten
    • , Namrata Gupta
    • , Cashell E Jaquish
    • , Andrew D Johnson
    • , Joshua P Lewis
    • , Xiaoming Liu
    • , Alisa K Manning
    • , George J Papanicolaou
    • , Achilleas N Pitsillides
    • , Kenneth M Rice
    • , William Salerno
    • , Colleen M Sitlani
    • , Nicholas L Smith
    • , NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
    • , The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
    • , TOPMed Hematology and Hemostasis Working Group
    • , CHARGE Analysis and Bioinformatics Working Group
    • , Susan R Heckbert
    • , Cathy C Laurie
    • , Braxton D Mitchell
    • , Ramachandran S Vasan
    • , Stephen S Rich
    • , Jerome I Rotter
    • , James G Wilson
    • , Eric Boerwinkle
    • , Bruce M Psaty
    •  & L Adrienne Cupples

News & Views

  • News & Views |

    High-resolution maps of enhancer–promoter interactions in rare primary human T cell subsets and coronary artery smooth muscle cells link variants associated with autoimmune and cardiovascular diseases to target genes. This represents an important step forward for mapping genes involved in complex diseases.

    • Gosia Trynka
  • News & Views |

    Human-derived tumor models are becoming popular in the context of personalized medicine, but a new study shows that these models could be less representative of primary tumors than previously thought, particularly when using late passages.

    • Carlos Villacorta-Martin
    • , Amanda J Craig
    •  & Augusto Villanueva

Editorial

  • Editorial |

    Citation of prior publications is essential both to claim that knowledge is needed in your area of research and to establish that you have indeed advanced understanding substantially in that area. The journal deplores and will decline to consider manuscripts that fail to identify the key findings of published articles and that—deliberately or inadvertently—omit the reason the prior work is cited.

Corrigendum

  • Corrigendum |

    • Dominik Glodzik
    • , Sandro Morganella
    • , Helen Davies
    • , Peter T Simpson
    • , Yilong Li
    • , Xueqing Zou
    • , Javier Diez-Perez
    • , Johan Staaf
    • , Ludmil B Alexandrov
    • , Marcel Smid
    • , Arie B Brinkman
    • , Inga Hansine Rye
    • , Hege Russnes
    • , Keiran Raine
    • , Colin A Purdie
    • , Sunil R Lakhani
    • , Alastair M Thompson
    • , Ewan Birney
    • , Hendrik G Stunnenberg
    • , Marc J van de Vijver
    • , John W M Martens
    • , Anne-Lise Børresen-Dale
    • , Andrea L Richardson
    • , Gu Kong
    • , Alain Viari
    • , Douglas Easton
    • , Gerard Evan
    • , Peter J Campbell
    • , Michael R Stratton
    •  & Serena Nik-Zainal
  • Corrigendum |

    • Chi A Ma
    • , Jeffrey R Stinson
    • , Yuan Zhang
    • , Jordan K Abbott
    • , Michael A Weinreich
    • , Pia J Hauk
    • , Paul R Reynolds
    • , Jonathan J Lyons
    • , Celeste G Nelson
    • , Elisa Ruffo
    • , Batsukh Dorjbal
    • , Salomé Glauzy
    • , Natsuko Yamakawa
    • , Swadhinya Arjunaraja
    • , Kelsey Voss
    • , Jennifer Stoddard
    • , Julie Niemela
    • , Yu Zhang
    • , Sergio D Rosenzweig
    • , Joshua J McElwee
    • , Thomas DiMaggio
    • , Helen F Matthews
    • , Nina Jones
    • , Kelly D Stone
    • , Alejandro Palma
    • , Matías Oleastro
    • , Emma Prieto
    • , Andrea R Bernasconi
    • , Geronimo Dubra
    • , Silvia Danielian
    • , Jonathan Zaiat
    • , Marcelo A Marti
    • , Brian Kim
    • , Megan A Cooper
    • , Neil D Romberg
    • , Eric Meffre
    • , Erwin W Gelfand
    • , Andrew L Snow
    •  & Joshua D Milner

Erratum

  • Erratum |

    • David Brocks
    • , Christopher R Schmidt
    • , Michael Daskalakis
    • , Hyo Sik Jang
    • , Nakul M Shah
    • , Daofeng Li
    • , Jing Li
    • , Bo Zhang
    • , Yiran Hou
    • , Sara Laudato
    • , Daniel B Lipka
    • , Johanna Schott
    • , Holger Bierhoff
    • , Yassen Assenov
    • , Monika Helf
    • , Alzbeta Ressnerova
    • , Md Saiful Islam
    • , Anders M Lindroth
    • , Simon Haas
    • , Marieke Essers
    • , Charles D Imbusch
    • , Benedikt Brors
    • , Ina Oehme
    • , Olaf Witt
    • , Michael Lübbert
    • , Jan-Philipp Mallm
    • , Karsten Rippe
    • , Rainer Will
    • , Dieter Weichenhan
    • , Georg Stoecklin
    • , Clarissa Gerhäuser
    • , Christopher C Oakes
    • , Ting Wang
    •  & Christoph Plass