Volume 49 Issue 5, 1 May 2017

Article

  • Article |

    Andrew Feinberg, John Goutsias and colleagues derive potential energy landscapes from bisulfite sequencing data and quantify DNA methylation stochasticity genome-wide using Shannon's entropy, identifying an association between entropy and chromatin structure. Their analysis highlights the information-theoretic nature of the epigenome and provides a methodology for studying its role in disease and aging.

    • Garrett Jenkinson
    • , Elisabet Pujadas
    • , John Goutsias
    •  & Andrew P Feinberg
  • Article |

    Julie Lessard and colleagues report that ATP-dependent SWI/SNF chromatin-remodeling complex subunit SMARCD2 is essential for granulocyte development. They find that Smarcd2-deficient mice fail to generate functioning neutrophils and eosinophils, and they determine that the divergent coiled-coil 1 and SWIB domains are responsible for functional specificity during granulocyte differentiation.

    • Pierre Priam
    • , Veneta Krasteva
    • , Philippe Rousseau
    • , Giovanni D'Angelo
    • , Louis Gaboury
    • , Guy Sauvageau
    •  & Julie A Lessard
  • Article |

    Juan Cadiñanos and colleagues perform an insertional mutagenesis screen with a single-copy inactivating Sleeping Beauty transposon to look for Pten-cooperating tumor suppressor genes in mice. They find novel candidate cancer genes, verify their clinical relevance in patient cohorts and functionally demonstrate their synergistic relationship to Pten in tumor suppression.

    • Jorge de la Rosa
    • , Julia Weber
    • , Mathias Josef Friedrich
    • , Yilong Li
    • , Lena Rad
    • , Hannes Ponstingl
    • , Qi Liang
    • , Sandra Bernaldo de Quirós
    • , Imran Noorani
    • , Emmanouil Metzakopian
    • , Alexander Strong
    • , Meng Amy Li
    • , Aurora Astudillo
    • , María Teresa Fernández-García
    • , María Soledad Fernández-García
    • , Gary J Hoffman
    • , Rocío Fuente
    • , George S Vassiliou
    • , Roland Rad
    • , Carlos López-Otín
    • , Allan Bradley
    •  & Juan Cadiñanos
  • Article |

    Shyam Prabhakar, Paul Robson, Iain Beehuat Tan and colleagues characterize the cellular heterogeneity of colorectal tumors and their microenvironment on the basis of single-cell RNA–seq data analyzed with their newly developed clustering algorithm, reference component analysis (RCA). Their analyses identify two subtypes of cancer-associated fibroblasts and further divide tumors into subgroups with divergent survival probabilities.

    • Huipeng Li
    • , Elise T Courtois
    • , Debarka Sengupta
    • , Yuliana Tan
    • , Kok Hao Chen
    • , Jolene Jie Lin Goh
    • , Say Li Kong
    • , Clarinda Chua
    • , Lim Kiat Hon
    • , Wah Siew Tan
    • , Mark Wong
    • , Paul Jongjoon Choi
    • , Lawrence J K Wee
    • , Axel M Hillmer
    • , Iain Beehuat Tan
    • , Paul Robson
    •  & Shyam Prabhakar
  • Article |

    Fanjiang Kong, Zhixi Tian, Xingliang Hou, Baohui Liu and colleagues report the cloning and functional characterization of J, the locus underlying the long-juvenile (LJ) trait that has enabled tropical cultivation of soybean. They show that J, an ortholog of Arabidopsis ELF3, downregulates the expression of E1, thereby promoting flowering under short-day conditions.

    • Sijia Lu
    • , Xiaohui Zhao
    • , Yilong Hu
    • , Shulin Liu
    • , Haiyang Nan
    • , Xiaoming Li
    • , Chao Fang
    • , Dong Cao
    • , Xinyi Shi
    • , Lingping Kong
    • , Tong Su
    • , Fengge Zhang
    • , Shichen Li
    • , Zheng Wang
    • , Xiaohui Yuan
    • , Elroy R Cober
    • , James L Weller
    • , Baohui Liu
    • , Xingliang Hou
    • , Zhixi Tian
    •  & Fanjiang Kong
  • Article |

    John Perry and colleagues identify genetic variants at 19 genomic regions associated with mosaic loss of the Y chromosome (mLOY) in blood. They further highlight a shared genetic architecture between mLOY and cancer susceptibility, and infer a causal effect of smoking on mLOY.

    • Daniel J Wright
    • , Felix R Day
    • , Nicola D Kerrison
    • , Florian Zink
    • , Alexia Cardona
    • , Patrick Sulem
    • , Deborah J Thompson
    • , Svanhvit Sigurjonsdottir
    • , Daniel F Gudbjartsson
    • , Agnar Helgason
    • , J Ross Chapman
    • , Steve P Jackson
    • , Claudia Langenberg
    • , Nicholas J Wareham
    • , Robert A Scott
    • , Unnur Thorsteindottir
    • , Ken K Ong
    • , Kari Stefansson
    •  & John R B Perry
  • Article |

    Ryan Emerson and colleagues report immunosequencing of the variable region of the TCRβ chain in 666 individuals with known cytomegalovirus (CMV) status. They show that CMV status and HLA genotype shape the T cell repertoire and demonstrate proof of principle that TCRβ sequencing can be used as a specific diagnostic of pathogen exposure.

    • Ryan O Emerson
    • , William S DeWitt
    • , Marissa Vignali
    • , Jenna Gravley
    • , Joyce K Hu
    • , Edward J Osborne
    • , Cindy Desmarais
    • , Mark Klinger
    • , Christopher S Carlson
    • , John A Hansen
    • , Mark Rieder
    •  & Harlan S Robins
  • Article |

    Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

    • Catherine M Phelan
    • , Karoline B Kuchenbaecker
    • , Jonathan P Tyrer
    • , Siddhartha P Kar
    • , Kate Lawrenson
    • , Stacey J Winham
    • , Joe Dennis
    • , Ailith Pirie
    • , Marjorie J Riggan
    • , Ganna Chornokur
    • , Madalene A Earp
    • , Paulo C Lyra Jr
    • , Janet M Lee
    • , Simon Coetzee
    • , Jonathan Beesley
    • , Lesley McGuffog
    • , Penny Soucy
    • , Ed Dicks
    • , Andrew Lee
    • , Daniel Barrowdale
    • , Julie Lecarpentier
    • , Goska Leslie
    • , Cora M Aalfs
    • , Katja K H Aben
    • , Marcia Adams
    • , Julian Adlard
    • , Irene L Andrulis
    • , Hoda Anton-Culver
    • , Natalia Antonenkova
    • , AOCS study group
    • , Gerasimos Aravantinos
    • , Norbert Arnold
    • , Banu K Arun
    • , Brita Arver
    • , Jacopo Azzollini
    • , Judith Balmaña
    • , Susana N Banerjee
    • , Laure Barjhoux
    • , Rosa B Barkardottir
    • , Yukie Bean
    • , Matthias W Beckmann
    • , Alicia Beeghly-Fadiel
    • , Javier Benitez
    • , Marina Bermisheva
    • , Marcus Q Bernardini
    • , Michael J Birrer
    • , Line Bjorge
    • , Amanda Black
    • , Kenneth Blankstein
    • , Marinus J Blok
    • , Clara Bodelon
    • , Natalia Bogdanova
    • , Anders Bojesen
    • , Bernardo Bonanni
    • , Åke Borg
    • , Angela R Bradbury
    • , James D Brenton
    • , Carole Brewer
    • , Louise Brinton
    • , Per Broberg
    • , Angela Brooks-Wilson
    • , Fiona Bruinsma
    • , Joan Brunet
    • , Bruno Buecher
    • , Ralf Butzow
    • , Saundra S Buys
    • , Trinidad Caldes
    • , Maria A Caligo
    • , Ian Campbell
    • , Rikki Cannioto
    • , Michael E Carney
    • , Terence Cescon
    • , Salina B Chan
    • , Jenny Chang-Claude
    • , Stephen Chanock
    • , Xiao Qing Chen
    • , Yoke-Eng Chiew
    • , Jocelyne Chiquette
    • , Wendy K Chung
    • , Kathleen B M Claes
    • , Thomas Conner
    • , Linda S Cook
    • , Jackie Cook
    • , Daniel W Cramer
    • , Julie M Cunningham
    • , Aimee A D'Aloisio
    • , Mary B Daly
    • , Francesca Damiola
    • , Sakaeva Dina Damirovna
    • , Agnieszka Dansonka-Mieszkowska
    • , Fanny Dao
    • , Rosemarie Davidson
    • , Anna DeFazio
    • , Capucine Delnatte
    • , Kimberly F Doheny
    • , Orland Diez
    • , Yuan Chun Ding
    • , Jennifer Anne Doherty
    • , Susan M Domchek
    • , Cecilia M Dorfling
    • , Thilo Dörk
    • , Laure Dossus
    • , Mercedes Duran
    • , Matthias Dürst
    • , Bernd Dworniczak
    • , Diana Eccles
    • , Todd Edwards
    • , Ros Eeles
    • , Ursula Eilber
    • , Bent Ejlertsen
    • , Arif B Ekici
    • , Steve Ellis
    • , Mingajeva Elvira
    • , EMBRACE Study
    • , Kevin H Eng
    • , Christoph Engel
    • , D Gareth Evans
    • , Peter A Fasching
    • , Sarah Ferguson
    • , Sandra Fert Ferrer
    • , James M Flanagan
    • , Zachary C Fogarty
    • , Renée T Fortner
    • , Florentia Fostira
    • , William D Foulkes
    • , George Fountzilas
    • , Brooke L Fridley
    • , Tara M Friebel
    • , Eitan Friedman
    • , Debra Frost
    • , Patricia A Ganz
    • , Judy Garber
    • , María J García
    • , Vanesa Garcia-Barberan
    • , Andrea Gehrig
    • , GEMO Study Collaborators
    • , Aleksandra Gentry-Maharaj
    • , Anne-Marie Gerdes
    • , Graham G Giles
    • , Rosalind Glasspool
    • , Gord Glendon
    • , Andrew K Godwin
    • , David E Goldgar
    • , Teodora Goranova
    • , Martin Gore
    • , Mark H Greene
    • , Jacek Gronwald
    • , Stephen Gruber
    • , Eric Hahnen
    • , Christopher A Haiman
    • , Niclas Håkansson
    • , Ute Hamann
    • , Thomas V O Hansen
    • , Patricia A Harrington
    • , Holly R Harris
    • , Jan Hauke
    • , HEBON Study
    • , Alexander Hein
    • , Alex Henderson
    • , Michelle A T Hildebrandt
    • , Peter Hillemanns
    • , Shirley Hodgson
    • , Claus K Høgdall
    • , Estrid Høgdall
    • , Frans B L Hogervorst
    • , Helene Holland
    • , Maartje J Hooning
    • , Karen Hosking
    • , Ruea-Yea Huang
    • , Peter J Hulick
    • , Jillian Hung
    • , David J Hunter
    • , David G Huntsman
    • , Tomasz Huzarski
    • , Evgeny N Imyanitov
    • , Claudine Isaacs
    • , Edwin S Iversen
    • , Louise Izatt
    • , Angel Izquierdo
    • , Anna Jakubowska
    • , Paul James
    • , Ramunas Janavicius
    • , Mats Jernetz
    • , Allan Jensen
    • , Uffe Birk Jensen
    • , Esther M John
    • , Sharon Johnatty
    • , Michael E Jones
    • , Päivi Kannisto
    • , Beth Y Karlan
    • , Anthony Karnezis
    • , Karin Kast
    • , KConFab Investigators
    • , Catherine J Kennedy
    • , Elza Khusnutdinova
    • , Lambertus A Kiemeney
    • , Johanna I Kiiski
    • , Sung-Won Kim
    • , Susanne K Kjaer
    • , Martin Köbel
    • , Reidun K Kopperud
    • , Torben A Kruse
    • , Jolanta Kupryjanczyk
    • , Ava Kwong
    • , Yael Laitman
    • , Diether Lambrechts
    • , Nerea Larrañaga
    • , Melissa C Larson
    • , Conxi Lazaro
    • , Nhu D Le
    • , Loic Le Marchand
    • , Jong Won Lee
    • , Shashikant B Lele
    • , Arto Leminen
    • , Dominique Leroux
    • , Jenny Lester
    • , Fabienne Lesueur
    • , Douglas A Levine
    • , Dong Liang
    • , Clemens Liebrich
    • , Jenna Lilyquist
    • , Loren Lipworth
    • , Jolanta Lissowska
    • , Karen H Lu
    • , Jan Lubinński
    • , Craig Luccarini
    • , Lene Lundvall
    • , Phuong L Mai
    • , Gustavo Mendoza-Fandiño
    • , Siranoush Manoukian
    • , Leon F A G Massuger
    • , Taymaa May
    • , Sylvie Mazoyer
    • , Jessica N McAlpine
    • , Valerie McGuire
    • , John R McLaughlin
    • , Iain McNeish
    • , Hanne Meijers-Heijboer
    • , Alfons Meindl
    • , Usha Menon
    • , Arjen R Mensenkamp
    • , Melissa A Merritt
    • , Roger L Milne
    • , Gillian Mitchell
    • , Francesmary Modugno
    • , Joanna Moes-Sosnowska
    • , Melissa Moffitt
    • , Marco Montagna
    • , Kirsten B Moysich
    • , Anna Marie Mulligan
    • , Jacob Musinsky
    • , Katherine L Nathanson
    • , Lotte Nedergaard
    • , Roberta B Ness
    • , Susan L Neuhausen
    • , Heli Nevanlinna
    • , Dieter Niederacher
    • , Robert L Nussbaum
    • , Kunle Odunsi
    • , Edith Olah
    • , Olufunmilayo I Olopade
    • , Håkan Olsson
    • , Curtis Olswold
    • , David M O'Malley
    • , Kai-ren Ong
    • , N Charlotte Onland-Moret
    • , OPAL study group
    • , Nicholas Orr
    • , Sandra Orsulic
    • , Ana Osorio
    • , Domenico Palli
    • , Laura Papi
    • , Tjoung-Won Park-Simon
    • , James Paul
    • , Celeste L Pearce
    • , Inge Søkilde Pedersen
    • , Petra H M Peeters
    • , Bernard Peissel
    • , Ana Peixoto
    • , Tanja Pejovic
    • , Liisa M Pelttari
    • , Jennifer B Permuth
    • , Paolo Peterlongo
    • , Lidia Pezzani
    • , Georg Pfeiler
    • , Kelly-Anne Phillips
    • , Marion Piedmonte
    • , Malcolm C Pike
    • , Anna M Piskorz
    • , Samantha R Poblete
    • , Timea Pocza
    • , Elizabeth M Poole
    • , Bruce Poppe
    • , Mary E Porteous
    • , Fabienne Prieur
    • , Darya Prokofyeva
    • , Elizabeth Pugh
    • , Miquel Angel Pujana
    • , Pascal Pujol
    • , Paolo Radice
    • , Johanna Rantala
    • , Christine Rappaport-Fuerhauser
    • , Gad Rennert
    • , Kerstin Rhiem
    • , Patricia Rice
    • , Andrea Richardson
    • , Mark Robson
    • , Gustavo C Rodriguez
    • , Cristina Rodríguez-Antona
    • , Jane Romm
    • , Matti A Rookus
    • , Mary Anne Rossing
    • , Joseph H Rothstein
    • , Anja Rudolph
    • , Ingo B Runnebaum
    • , Helga B Salvesen
    • , Dale P Sandler
    • , Minouk J Schoemaker
    • , Leigha Senter
    • , V Wendy Setiawan
    • , Gianluca Severi
    • , Priyanka Sharma
    • , Tameka Shelford
    • , Nadeem Siddiqui
    • , Lucy E Side
    • , Weiva Sieh
    • , Christian F Singer
    • , Hagay Sobol
    • , Honglin Song
    • , Melissa C Southey
    • , Amanda B Spurdle
    • , Zsofia Stadler
    • , Doris Steinemann
    • , Dominique Stoppa-Lyonnet
    • , Lara E Sucheston-Campbell
    • , Grzegorz Sukiennicki
    • , Rebecca Sutphen
    • , Christian Sutter
    • , Anthony J Swerdlow
    • , Csilla I Szabo
    • , Lukasz Szafron
    • , Yen Y Tan
    • , Jack A Taylor
    • , Muy-Kheng Tea
    • , Manuel R Teixeira
    • , Soo-Hwang Teo
    • , Kathryn L Terry
    • , Pamela J Thompson
    • , Liv Cecilie Vestrheim Thomsen
    • , Darcy L Thull
    • , Laima Tihomirova
    • , Anna V Tinker
    • , Marc Tischkowitz
    • , Silvia Tognazzo
    • , Amanda Ewart Toland
    • , Alicia Tone
    • , Britton Trabert
    • , Ruth C Travis
    • , Antonia Trichopoulou
    • , Nadine Tung
    • , Shelley S Tworoger
    • , Anne M van Altena
    • , David Van Den Berg
    • , Annemarie H van der Hout
    • , Rob B van der Luijt
    • , Mattias Van Heetvelde
    • , Els Van Nieuwenhuysen
    • , Elizabeth J van Rensburg
    • , Adriaan Vanderstichele
    • , Raymonda Varon-Mateeva
    • , Ana Vega
    • , Digna Velez Edwards
    • , Ignace Vergote
    • , Robert A Vierkant
    • , Joseph Vijai
    • , Athanassios Vratimos
    • , Lisa Walker
    • , Christine Walsh
    • , Dorothea Wand
    • , Shan Wang-Gohrke
    • , Barbara Wappenschmidt
    • , Penelope M Webb
    • , Clarice R Weinberg
    • , Jeffrey N Weitzel
    • , Nicolas Wentzensen
    • , Alice S Whittemore
    • , Juul T Wijnen
    • , Lynne R Wilkens
    • , Alicja Wolk
    • , Michelle Woo
    • , Xifeng Wu
    • , Anna H Wu
    • , Hannah Yang
    • , Drakoulis Yannoukakos
    • , Argyrios Ziogas
    • , Kristin K Zorn
    • , Steven A Narod
    • , Douglas F Easton
    • , Christopher I Amos
    • , Joellen M Schildkraut
    • , Susan J Ramus
    • , Laura Ottini
    • , Marc T Goodman
    • , Sue K Park
    • , Linda E Kelemen
    • , Harvey A Risch
    • , Mads Thomassen
    • , Kenneth Offit
    • , Jacques Simard
    • , Rita Katharina Schmutzler
    • , Dennis Hazelett
    • , Alvaro N Monteiro
    • , Fergus J Couch
    • , Andrew Berchuck
    • , Georgia Chenevix-Trench
    • , Ellen L Goode
    • , Thomas A Sellers
    • , Simon A Gayther
    • , Antonis C Antoniou
    •  & Paul D P Pharoah
  • Article |

    Christoph Klein and colleagues identify loss-of-function mutations in SMARCD2 (BAF60b) that lead to neutropenia, specific granule deficiency and myelodysplasia. They show that SMARCD2 controls differentiation of myeloid–erythroid progenitor cells through interaction with CEBPɛ and that reduced SMARCD2 levels cause transcription and chromatin alterations in acute myeloid leukemia cells.

    • Maximilian Witzel
    • , Daniel Petersheim
    • , Yanxin Fan
    • , Ehsan Bahrami
    • , Tomas Racek
    • , Meino Rohlfs
    • , Jacek Puchałka
    • , Christian Mertes
    • , Julien Gagneur
    • , Christoph Ziegenhain
    • , Wolfgang Enard
    • , Asbjørg Stray-Pedersen
    • , Peter D Arkwright
    • , Miguel R Abboud
    • , Vahid Pazhakh
    • , Graham J Lieschke
    • , Peter M Krawitz
    • , Maik Dahlhoff
    • , Marlon R Schneider
    • , Eckhard Wolf
    • , Hans-Peter Horny
    • , Heinrich Schmidt
    • , Alejandro A Schäffer
    •  & Christoph Klein
  • Article |

    Ira Hall, Donald Conrad, the GTEx consortium and colleagues identify 23,602 high-confidence structural variants (SVs) and 24,884 cis expression quantitative trait loci (eQTLs) across 13 human tissues. They estimate that SVs are the causal variant at 3.5–6.8% of eQTLs and identify 789 SVs predicted to directly alter gene expression, most of which are noncoding variants in regulatory elements.

    • Colby Chiang
    • , Alexandra J Scott
    • , Joe R Davis
    • , Emily K Tsang
    • , Xin Li
    • , Yungil Kim
    • , Tarik Hadzic
    • , Farhan N Damani
    • , Liron Ganel
    • , GTEx Consortium
    • , Stephen B Montgomery
    • , Alexis Battle
    • , Donald F Conrad
    •  & Ira M Hall
  • Article |

    Chris Spencer, Eleanor Barnes and colleagues use human genotyping arrays and whole-genome viral sequencing to perform a systematic genome-to-genome study of 542 individuals chronically infected with hepatitis C virus (HCV). They show that both HLA alleles and genes encoding factors of the innate immune system drive viral genome polymorphism and that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific polymorphism encoded in the HCV polyprotein.

    • M Azim Ansari
    • , Vincent Pedergnana
    • , Camilla L C Ip
    • , Andrea Magri
    • , Annette Von Delft
    • , David Bonsall
    • , Nimisha Chaturvedi
    • , Istvan Bartha
    • , David Smith
    • , George Nicholson
    • , Gilean McVean
    • , Amy Trebes
    • , Paolo Piazza
    • , Jacques Fellay
    • , Graham Cooke
    • , Graham R Foster
    • , STOP-HCV Consortium
    • , Eleanor Barnes
    • , Jonathan Ball
    • , Diana Brainard
    • , Gary Burgess
    • , Graham Cooke
    • , John Dillon
    • , Graham R Foster
    • , Charles Gore
    • , Neil Guha
    • , Rachel Halford
    • , Cham Herath
    • , Chris Holmes
    • , Anita Howe
    • , Emma Hudson
    • , William Irving
    • , Salim Khakoo
    • , Paul Klenerman
    • , Diana Koletzki
    • , Natasha Martin
    • , Benedetta Massetto
    • , Tamyo Mbisa
    • , John McHutchison
    • , Jane McKeating
    • , John McLauchlan
    • , Alec Miners
    • , Andrea Murray
    • , Peter Shaw
    • , Peter Simmonds
    • , Chris C A Spencer
    • , Paul Targett-Adams
    • , Emma Thomson
    • , Peter Vickerman
    • , Nicole Zitzmann
    • , Emma Hudson
    • , John McLauchlan
    • , Peter Simmonds
    • , Rory Bowden
    • , Paul Klenerman
    • , Eleanor Barnes
    •  & Chris C A Spencer
  • Article | | open

    Qiang Xu and colleagues sequence four citrus species de novo, along with 100 accessions, including primitive, wild and cultivated citrus. Their genomic analyses associate the CitRWP gene with polyembryony and suggest that regions harboring energy- and reproduction-associated genes are probably under selection in cultivated citrus.

    • Xia Wang
    • , Yuantao Xu
    • , Siqi Zhang
    • , Li Cao
    • , Yue Huang
    • , Junfeng Cheng
    • , Guizhi Wu
    • , Shilin Tian
    • , Chunli Chen
    • , Yan Liu
    • , Huiwen Yu
    • , Xiaoming Yang
    • , Hong Lan
    • , Nan Wang
    • , Lun Wang
    • , Jidi Xu
    • , Xiaolin Jiang
    • , Zongzhou Xie
    • , Meilian Tan
    • , Robert M Larkin
    • , Ling-Ling Chen
    • , Bin-Guang Ma
    • , Yijun Ruan
    • , Xiuxin Deng
    •  & Qiang Xu
  • Article |

    Francesco Cucca, Stephen Montgomery and colleagues identify regulatory variants that influence gene expression and splicing using whole-genome and transcriptome sequence data from 624 Sardinians. They find a high frequency of splicing and expression quantitative trait loci near genes involved in malarial resistance and multiple sclerosis.

    • Mauro Pala
    • , Zachary Zappala
    • , Mara Marongiu
    • , Xin Li
    • , Joe R Davis
    • , Roberto Cusano
    • , Francesca Crobu
    • , Kimberly R Kukurba
    • , Michael J Gloudemans
    • , Frederic Reinier
    • , Riccardo Berutti
    • , Maria G Piras
    • , Antonella Mulas
    • , Magdalena Zoledziewska
    • , Michele Marongiu
    • , Elena P Sorokin
    • , Gaelen T Hess
    • , Kevin S Smith
    • , Fabio Busonero
    • , Andrea Maschio
    • , Maristella Steri
    • , Carlo Sidore
    • , Serena Sanna
    • , Edoardo Fiorillo
    • , Michael C Bassik
    • , Stephen J Sawcer
    • , Alexis Battle
    • , John Novembre
    • , Chris Jones
    • , Andrea Angius
    • , Gonçalo R Abecasis
    • , David Schlessinger
    • , Francesco Cucca
    •  & Stephen B Montgomery

Letter

  • Letter |

    Kari Stefansson, Unnur Styrkarsdottir and colleagues identify rare genotypes in COMP and CHADL associated with high risk of total hip replacement due to osteoarthritis. The high odds ratios associated with these rare risk genotypes suggest that they may represent Mendelian forms of osteoarthritis.

    • Unnur Styrkarsdottir
    • , Hannes Helgason
    • , Asgeir Sigurdsson
    • , Gudmundur L Norddahl
    • , Arna B Agustsdottir
    • , Louise N Reynard
    • , Amanda Villalvilla
    • , Gisli H Halldorsson
    • , Aslaug Jonasdottir
    • , Audur Magnusdottir
    • , Asmundur Oddson
    • , Gerald Sulem
    • , Florian Zink
    • , Gardar Sveinbjornsson
    • , Agnar Helgason
    • , Hrefna S Johannsdottir
    • , Anna Helgadottir
    • , Hreinn Stefansson
    • , Solveig Gretarsdottir
    • , Thorunn Rafnar
    • , Ina S Almdahl
    • , Anne Brækhus
    • , Tormod Fladby
    • , Geir Selbæk
    • , Farhad Hosseinpanah
    • , Fereidoun Azizi
    • , Jung Min Koh
    • , Nelson L S Tang
    • , Maryam S Daneshpour
    • , Jose I Mayordomo
    • , Corrine Welt
    • , Peter S Braund
    • , Nilesh J Samani
    • , Lambertus A Kiemeney
    • , L Stefan Lohmander
    • , Claus Christiansen
    • , Ole A Andreassen
    • , arcOGEN consortium
    • , Olafur Magnusson
    • , Gisli Masson
    • , Augustine Kong
    • , Ingileif Jonsdottir
    • , Daniel Gudbjartsson
    • , Patrick Sulem
    • , Helgi Jonsson
    • , John Loughlin
    • , Thorvaldur Ingvarsson
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  • Letter |

    Beatrice Melin, Richard Houlston, Melissa Bondy and colleagues report results of a large-scale genome-wide association study of glioma. They identify five new risk loci for glioblastoma and eight new risk loci for non-glioblastoma tumors, highlighting distinct genetic etiologies for these two glioma subtypes.

    • Beatrice S Melin
    • , Jill S Barnholtz-Sloan
    • , Margaret R Wrensch
    • , Christoffer Johansen
    • , Dora Il'yasova
    • , Ben Kinnersley
    • , Quinn T Ostrom
    • , Karim Labreche
    • , Yanwen Chen
    • , Georgina Armstrong
    • , Yanhong Liu
    • , Jeanette E Eckel-Passow
    • , Paul A Decker
    • , Marianne Labussière
    • , Ahmed Idbaih
    • , Khe Hoang-Xuan
    • , Anna-Luisa Di Stefano
    • , Karima Mokhtari
    • , Jean-Yves Delattre
    • , Peter Broderick
    • , Pilar Galan
    • , Konstantinos Gousias
    • , Johannes Schramm
    • , Minouk J Schoemaker
    • , Sarah J Fleming
    • , Stefan Herms
    • , Stefanie Heilmann
    • , Markus M Nöthen
    • , Heinz-Erich Wichmann
    • , Stefan Schreiber
    • , Anthony Swerdlow
    • , Mark Lathrop
    • , Matthias Simon
    • , Marc Sanson
    • , Ulrika Andersson
    • , Preetha Rajaraman
    • , Stephen Chanock
    • , Martha Linet
    • , Zhaoming Wang
    • , Meredith Yeager
    • , GliomaScan Consortium
    • , John K Wiencke
    • , Helen Hansen
    • , Lucie McCoy
    • , Terri Rice
    • , Matthew L Kosel
    • , Hugues Sicotte
    • , Christopher I Amos
    • , Jonine L Bernstein
    • , Faith Davis
    • , Dan Lachance
    • , Ching Lau
    • , Ryan T Merrell
    • , Joellen Shildkraut
    • , Francis Ali-Osman
    • , Siegal Sadetzki
    • , Michael Scheurer
    • , Sanjay Shete
    • , Rose K Lai
    • , Elizabeth B Claus
    • , Sara H Olson
    • , Robert B Jenkins
    • , Richard S Houlston
    •  & Melissa L Bondy
  • Letter |

    Kenneth Olsen, Ana Caicedo and colleagues analyze whole-genome sequences of two strains of weedy relatives of cultivated rice. They find that weedy rice strains are primarily descended from domesticated ancestors and that few genetic differences accompanied the emergence of weediness traits.

    • Lin-Feng Li
    • , Ya-Ling Li
    • , Yulin Jia
    • , Ana L Caicedo
    •  & Kenneth M Olsen
  • Letter |

    Shamil Sunyaev, David Beier and colleagues report an analysis of the fitness effects of heterozygous protein-truncating variants from the Exome Aggregation Consortium. They find that high heterozygous selection coefficients are enriched in Mendelian disease-associated genes and essential mouse genes, suggesting that this coefficient can be used to prioritize candidate disease-associated genes from clinical exome-sequencing data.

    • Christopher A Cassa
    • , Donate Weghorn
    • , Daniel J Balick
    • , Daniel M Jordan
    • , David Nusinow
    • , Kaitlin E Samocha
    • , Anne O'Donnell-Luria
    • , Daniel G MacArthur
    • , Mark J Daly
    • , David R Beier
    •  & Shamil R Sunyaev
  • Letter |

    Jacob George and colleagues examine whether the association of the IFNL3IFNL4 region with hepatic inflammation and fibrosis is mediated by IFN-λ3 or IFN-λ4. They find greater hepatic inflammation, fibrosis progression rate and hepatic infiltration of immune cells in individuals with the risk haplotype that produces IFN-λ3 but not IFN-λ4.

    • Mohammed Eslam
    • , Duncan McLeod
    • , Kebitsaone Simon Kelaeng
    • , Alessandra Mangia
    • , Thomas Berg
    • , Khaled Thabet
    • , William L Irving
    • , Gregory J Dore
    • , David Sheridan
    • , Henning Grønbæk
    • , Maria Lorena Abate
    • , Rune Hartmann
    • , Elisabetta Bugianesi
    • , Ulrich Spengler
    • , Angela Rojas
    • , David R Booth
    • , Martin Weltman
    • , Lindsay Mollison
    • , Wendy Cheng
    • , Stephen Riordan
    • , Hema Mahajan
    • , Janett Fischer
    • , Jacob Nattermann
    • , Mark W Douglas
    • , Christopher Liddle
    • , Elizabeth Powell
    • , Manuel Romero-Gomez
    • , Jacob George
    • , the International Liver Disease Genetics Consortium (ILDGC)
    • , Mayada Metwally
    • , Rose White
    • , Rocio Gallego-Duran
    • , Reynold Leung
    • , Neha Mahajan
    • , Margaret Bassendine
    • , Antony Rahme
    • , Chiara Rosso
    • , Lavinia Mezzabotta
    • , Barbara Malik
    • , Gail Matthews
    • , Anastasia Asimakopoulos
    • , Tanya Applegate
    • , Jason Grebely
    • , Vincenzo Fragomeli
    • , Julie R Jonsson
    •  & Rosanna Santoro
  • Letter |

    Michael Taylor, Marco Marra and colleagues analyze spatial tumor heterogeneity in 9 medulloblastomas, 16 high-grade gliomas and 10 renal cell carcinomas, using a combination of transcriptomic and genomic profiling of multiregional biopsies. They find that medulloblastomas have spatially homogeneous transcriptomes, whereas somatic mutations that affect genes suitable for targeted therapeutics are spatially heterogeneous.

    • A Sorana Morrissy
    • , Florence M G Cavalli
    • , Marc Remke
    • , Vijay Ramaswamy
    • , David J H Shih
    • , Borja L Holgado
    • , Hamza Farooq
    • , Laura K Donovan
    • , Livia Garzia
    • , Sameer Agnihotri
    • , Erin N Kiehna
    • , Eloi Mercier
    • , Chelsea Mayoh
    • , Simon Papillon-Cavanagh
    • , Hamid Nikbakht
    • , Tenzin Gayden
    • , Jonathon Torchia
    • , Daniel Picard
    • , Diana M Merino
    • , Maria Vladoiu
    • , Betty Luu
    • , Xiaochong Wu
    • , Craig Daniels
    • , Stuart Horswell
    • , Yuan Yao Thompson
    • , Volker Hovestadt
    • , Paul A Northcott
    • , David T W Jones
    • , John Peacock
    • , Xin Wang
    • , Stephen C Mack
    • , Jüri Reimand
    • , Steffen Albrecht
    • , Adam M Fontebasso
    • , Nina Thiessen
    • , Yisu Li
    • , Jacqueline E Schein
    • , Darlene Lee
    • , Rebecca Carlsen
    • , Michael Mayo
    • , Kane Tse
    • , Angela Tam
    • , Noreen Dhalla
    • , Adrian Ally
    • , Eric Chuah
    • , Young Cheng
    • , Patrick Plettner
    • , Haiyan I Li
    • , Richard D Corbett
    • , Tina Wong
    • , William Long
    • , James Loukides
    • , Pawel Buczkowicz
    • , Cynthia E Hawkins
    • , Uri Tabori
    • , Brian R Rood
    • , John S Myseros
    • , Roger J Packer
    • , Andrey Korshunov
    • , Peter Lichter
    • , Marcel Kool
    • , Stefan M Pfister
    • , Ulrich Schüller
    • , Peter Dirks
    • , Annie Huang
    • , Eric Bouffet
    • , James T Rutka
    • , Gary D Bader
    • , Charles Swanton
    • , Yusanne Ma
    • , Richard A Moore
    • , Andrew J Mungall
    • , Jacek Majewski
    • , Steven J M Jones
    • , Sunit Das
    • , David Malkin
    • , Nada Jabado
    • , Marco A Marra
    •  & Michael D Taylor

News & Views

  • News & Views |

    A new resequencing analysis of weedy rice (Oryza sativa L.) biotypes illuminates distinct evolutionary paths and outcomes of de-domestication and ferality. This largest effort to date in weedy plant genomics gives a better understanding of weediness while also providing a promising source of alleles for rice breeding.

    • C Neal Stewart Jr
  • News & Views |

    Mammalian SWI/SNF complexes have critical roles in development and differentiation, and are implicated in the pathogenesis of several diseases; however, the mechanisms underpinning disease manifestation and the specificity of the subunits mutated are incompletely understood. Newly identified loss-of-function mutations in the SMARCD2 gene (part of the SMARCD1, SMARCD2 and SMARCD3 paralog family) reveal an evolutionarily conserved role specifically for the SMARCD2 subunit in granulopoiesis, and further investigation implicates the CEBPɛ transcription factor as a key effector of this specific function.

    • Brittany C Michel
    •  & Cigall Kadoch
  • News & Views |

    An unbiased genome-to-genome analysis in chronic hepatitis C virus (HCV) infection confirms the innate and adaptive arms of the immune system as drivers of viral evolution. Viral adaptation has a critical role in the interaction between host and pathogen and has important clinical implications for infection outcome.

    • Silvana Gaudieri
    •  & Michaela Lucas

Editorial

  • Editorial |

    With the advent of precision genome editing, the ability to modify living organisms has proceeded with remarkable speed and breadth. Any application of this technology to the human germ line must be tightly coupled to deliberate consideration of the consequences, both scientific and social, of introducing heritable alterations to the human population. We recommend constant oversight and evaluation of human germline genome editing to balance prudence with discovery, and risk with progress.