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
    • , 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
  • Commentary |

    Genetic variants have been associated with myriad molecular phenotypes that provide new insight into the range of mechanisms underlying genetic traits and diseases. Identifying any particular genetic variant's cascade of effects, from molecule to individual, requires assaying multiple layers of molecular complexity. We introduce the Enhancing GTEx (eGTEx) project that extends the GTEx project to combine gene expression with additional intermediate molecular measurements on the same tissues to provide a resource for studying how genetic differences cascade through molecular phenotypes to impact human health.

    • Barbara E Stranger
    • , Lori E Brigham
    • , Richard Hasz
    • , Marcus Hunter
    • , Christopher Johns
    • , Mark Johnson
    • , Gene Kopen
    • , William F Leinweber
    • , John T Lonsdale
    • , Alisa McDonald
    • , Bernadette Mestichelli
    • , Kevin Myer
    • , Brian Roe
    • , Michael Salvatore
    • , Saboor Shad
    • , Jeffrey A Thomas
    • , Gary Walters
    • , Michael Washington
    • , Joseph Wheeler
    • , Jason Bridge
    • , Barbara A Foster
    • , Bryan M Gillard
    • , Ellen Karasik
    • , Rachna Kumar
    • , Mark Miklos
    • , Michael T Moser
    • , Scott D Jewell
    • , Robert G Montroy
    • , Daniel C Rohrer
    • , Dana R Valley
    • , David A Davis
    • , Deborah C Mash
    • , Sarah E Gould
    • , Ping Guan
    • , Susan Koester
    • , A Roger Little
    • , Casey Martin
    • , Helen M Moore
    • , Abhi Rao
    • , Jeffery P Struewing
    • , Simona Volpi
    • , Kasper D Hansen
    • , Peter F Hickey
    • , Lindsay F Rizzardi
    • , Lei Hou
    • , Yaping Liu
    • , Benoit Molinie
    • , Yongjin Park
    • , Nicola Rinaldi
    • , Li Wang
    • , Nicholas Van Wittenberghe
    • , Melina Claussnitzer
    • , Ellen T Gelfand
    • , Qin Li
    • , Sandra Linder
    • , Rui Zhang
    • , Kevin S Smith
    • , Emily K Tsang
    • , Lin S Chen
    • , Kathryn Demanelis
    • , Jennifer A Doherty
    • , Farzana Jasmine
    • , Muhammad G Kibriya
    • , Lihua Jiang
    • , Shin Lin
    • , Meng Wang
    • , Ruiqi Jian
    • , Xiao Li
    • , Joanne Chan
    • , Daniel Bates
    • , Morgan Diegel
    • , Jessica Halow
    • , Eric Haugen
    • , Audra Johnson
    • , Rajinder Kaul
    • , Kristen Lee
    • , Matthew T Maurano
    • , Jemma Nelson
    • , Fidencio J Neri
    • , Richard Sandstrom
    • , Marian S Fernando
    • , Caroline Linke
    • , Meritxell Oliva
    • , Andrew Skol
    • , Fan Wu
    • , Joshua M Akey
    • , Andrew P Feinberg
    • , Jin Billy Li
    • , Brandon L Pierce
    • , John A Stamatoyannopoulos
    • , Hua Tang
    • , Kristin G Ardlie
    • , Manolis Kellis
    • , Michael P Snyder
    •  & Stephen B Montgomery
  • Commentary
    | Open Access

    • Malachi Griffith
    • , Nicholas C Spies
    • , Kilannin Krysiak
    • , Joshua F McMichael
    • , Adam C Coffman
    • , Arpad M Danos
    • , Benjamin J Ainscough
    • , Cody A Ramirez
    • , Damian T Rieke
    • , Lynzey Kujan
    • , Erica K Barnell
    • , Alex H Wagner
    • , Zachary L Skidmore
    • , Amber Wollam
    • , Connor J Liu
    • , Martin R Jones
    • , Rachel L Bilski
    • , Robert Lesurf
    • , Yan-Yang Feng
    • , Nakul M Shah
    • , Melika Bonakdar
    • , Lee Trani
    • , Matthew Matlock
    • , Avinash Ramu
    • , Katie M Campbell
    • , Gregory C Spies
    • , Aaron P Graubert
    • , Karthik Gangavarapu
    • , James M Eldred
    • , David E Larson
    • , Jason R Walker
    • , Benjamin M Good
    • , Chunlei Wu
    • , Andrew I Su
    • , Rodrigo Dienstmann
    • , Adam A Margolin
    • , David Tamborero
    • , Nuria Lopez-Bigas
    • , Steven J M Jones
    • , Ron Bose
    • , David H Spencer
    • , Lukas D Wartman
    • , Richard K Wilson
    • , Elaine R Mardis
    •  & Obi L Griffith
  • Commentary |

    Sanwen Huang, Detlef Weigel, Roger Beachy and Jiayang Li propose a regulatory framework for precision breeding with genome-edited crops. They argue that society should benefit from the latest advances in plant genetics and genomics.

    • Sanwen Huang
    • , Detlef Weigel
    • , Roger N Beachy
    •  & Jiayang Li
  • Commentary
    | Open Access

    Paul Flicek and colleagues provide an update on the European Genome-phenome Archive (EGA), a service of the European Bioinformatics Institute (EMBL-EBI) and the Center for Genome Regulation (CRG). The authors describe the EGA policies and infrastructure, how access decisions are made, methods for data submission and future plans for expansion of this database.

    • Ilkka Lappalainen
    • , Jeff Almeida-King
    • , Vasudev Kumanduri
    • , Alexander Senf
    • , John Dylan Spalding
    • , Saif ur-Rehman
    • , Gary Saunders
    • , Jag Kandasamy
    • , Mario Caccamo
    • , Rasko Leinonen
    • , Brendan Vaughan
    • , Thomas Laurent
    • , Francis Rowland
    • , Pablo Marin-Garcia
    • , Jonathan Barker
    • , Petteri Jokinen
    • , Angel Carreño Torres
    • , Jordi Rambla de Argila
    • , Oscar Martinez Llobet
    • , Ignacio Medina
    • , Marc Sitges Puy
    • , Mario Alberich
    • , Sabela de la Torre
    • , Arcadi Navarro
    • , Justin Paschall
    •  & Paul Flicek
  • Commentary
    | Open Access

    Dina Paltoo, Laura Lyman Rodriguez, Michael Feolo and colleagues present their analysis of the usefulness and impact of the first seven years of data sharing via the dbGaP repository and announce the extension of data-sharing provisions to other types of research funded by the NIH.

    • Dina N Paltoo
    • , Laura Lyman Rodriguez
    • , Michael Feolo
    • , Elizabeth Gillanders
    • , Erin M Ramos
    • , Joni L Rutter
    • , Stephen Sherry
    • , Vivian Ota Wang
    • , Alice Bailey
    • , Rebecca Baker
    • , Mark Caulder
    • , Emily L Harris
    • , Kristofor Langlais
    • , Hilary Leeds
    • , Erin Luetkemeier
    • , Taunton Paine
    • , Tamar Roomian
    • , Kimberly Tryka
    • , Amy Patterson
    •  & Eric D Green
  • Commentary
    | Open Access

    Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases.

    • Kyle Chang
    • , Chad J Creighton
    • , Caleb Davis
    • , Lawrence Donehower
    • , Jennifer Drummond
    • , David Wheeler
    • , Adrian Ally
    • , Miruna Balasundaram
    • , Inanc Birol
    • , Yaron S N Butterfield
    • , Andy Chu
    • , Eric Chuah
    • , Hye-Jung E Chun
    • , Noreen Dhalla
    • , Ranabir Guin
    • , Martin Hirst
    • , Carrie Hirst
    • , Robert A Holt
    • , Steven J M Jones
    • , Darlene Lee
    • , Haiyan I Li
    • , Marco A Marra
    • , Michael Mayo
    • , Richard A Moore
    • , Andrew J Mungall
    • , A Gordon Robertson
    • , Jacqueline E Schein
    • , Payal Sipahimalani
    • , Angela Tam
    • , Nina Thiessen
    • , Richard J Varhol
    • , Rameen Beroukhim
    • , Ami S Bhatt
    • , Angela N Brooks
    • , Andrew D Cherniack
    • , Samuel S Freeman
    • , Stacey B Gabriel
    • , Elena Helman
    • , Joonil Jung
    • , Matthew Meyerson
    • , Akinyemi I Ojesina
    • , Chandra Sekhar Pedamallu
    • , Gordon Saksena
    • , Steven E Schumacher
    • , Barbara Tabak
    • , Travis Zack
    • , Eric S Lander
    • , Christopher A Bristow
    • , Angela Hadjipanayis
    • , Psalm Haseley
    • , Raju Kucherlapati
    • , Semin Lee
    • , Eunjung Lee
    • , Lovelace J Luquette
    • , Harshad S Mahadeshwar
    • , Angeliki Pantazi
    • , Michael Parfenov
    • , Peter J Park
    • , Alexei Protopopov
    • , Xiaojia Ren
    • , Netty Santoso
    • , Jonathan Seidman
    • , Sahil Seth
    • , Xingzhi Song
    • , Jiabin Tang
    • , Ruibin Xi
    • , Andrew W Xu
    • , Lixing Yang
    • , Dong Zeng
    • , J Todd Auman
    • , Saianand Balu
    • , Elizabeth Buda
    • , Cheng Fan
    • , Katherine A Hoadley
    • , Corbin D Jones
    • , Shaowu Meng
    • , Piotr A Mieczkowski
    • , Joel S Parker
    • , Charles M Perou
    • , Jeffrey Roach
    • , Yan Shi
    • , Grace O Silva
    • , Donghui Tan
    • , Umadevi Veluvolu
    • , Scot Waring
    • , Matthew D Wilkerson
    • , Junyuan Wu
    • , Wei Zhao
    • , Tom Bodenheimer
    • , D Neil Hayes
    • , Alan P Hoyle
    • , Stuart R Jeffreys
    • , Lisle E Mose
    • , Janae V Simons
    • , Mathew G Soloway
    • , Stephen B Baylin
    • , Benjamin P Berman
    • , Moiz S Bootwalla
    • , Ludmila Danilova
    • , James G Herman
    • , Toshinori Hinoue
    • , Peter W Laird
    • , Suhn K Rhie
    • , Hui Shen
    • , Timothy Triche
    • , Daniel J Weisenberger
    • , Scott L Carter
    • , Kristian Cibulskis
    • , Lynda Chin
    • , Jianhua Zhang
    • , Gad Getz
    • , Carrie Sougnez
    • , Min Wang
    • , Gordon Saksena
    • , Scott L Carter
    • , Kristian Cibulskis
    • , Lynda Chin
    • , Jianhua Zhang
    • , Gad Getz
    • , Huyen Dinh
    • , Harsha Vardhan Doddapaneni
    • , Richard Gibbs
    • , Preethi Gunaratne
    • , Yi Han
    • , Divya Kalra
    • , Christie Kovar
    • , Lora Lewis
    • , Margaret Morgan
    • , Donna Morton
    • , Donna Muzny
    • , Jeffrey Reid
    • , Liu Xi
    • , Juok Cho
    • , Daniel DiCara
    • , Scott Frazer
    • , Nils Gehlenborg
    • , David I Heiman
    • , Jaegil Kim
    • , Michael S Lawrence
    • , Pei Lin
    • , Yingchun Liu
    • , Michael S Noble
    • , Petar Stojanov
    • , Doug Voet
    • , Hailei Zhang
    • , Lihua Zou
    • , Chip Stewart
    • , Brady Bernard
    • , Ryan Bressler
    • , Andrea Eakin
    • , Lisa Iype
    • , Theo Knijnenburg
    • , Roger Kramer
    • , Richard Kreisberg
    • , Kalle Leinonen
    • , Jake Lin
    • , Yuexin Liu
    • , Michael Miller
    • , Sheila M Reynolds
    • , Hector Rovira
    • , Ilya Shmulevich
    • , Vesteinn Thorsson
    • , Da Yang
    • , Wei Zhang
    • , Samirkumar Amin
    • , Chang-Jiun Wu
    • , Chia-Chin Wu
    • , Rehan Akbani
    • , Kenneth Aldape
    • , Keith A Baggerly
    • , Bradley Broom
    • , Tod D Casasent
    • , James Cleland
    • , Chad Creighton
    • , Deepti Dodda
    • , Mary Edgerton
    • , Leng Han
    • , Shelley M Herbrich
    • , Zhenlin Ju
    • , Hoon Kim
    • , Seth Lerner
    • , Jun Li
    • , Han Liang
    • , Wenbin Liu
    • , Philip L Lorenzi
    • , Yiling Lu
    • , James Melott
    • , Gordon B Mills
    • , Lam Nguyen
    • , Xiaoping Su
    • , Roeland Verhaak
    • , Wenyi Wang
    • , John N Weinstein
    • , Andrew Wong
    • , Yang Yang
    • , Jun Yao
    • , Rong Yao
    • , Kosuke Yoshihara
    • , Yuan Yuan
    • , Alfred K Yung
    • , Nianxiang Zhang
    • , Siyuan Zheng
    • , Michael Ryan
    • , David W Kane
    • , B Arman Aksoy
    • , Giovanni Ciriello
    • , Gideon Dresdner
    • , Jianjiong Gao
    • , Benjamin Gross
    • , Anders Jacobsen
    • , Andre Kahles
    • , Marc Ladanyi
    • , William Lee
    • , Kjong-Van Lehmann
    • , Martin L Miller
    • , Ricardo Ramirez
    • , Gunnar Rätsch
    • , Boris Reva
    • , Chris Sander
    • , Nikolaus Schultz
    • , Yasin Senbabaoglu
    • , Ronglai Shen
    • , Rileen Sinha
    • , S Onur Sumer
    • , Yichao Sun
    • , Barry S Taylor
    • , Nils Weinhold
    • , Suzanne Fei
    • , Paul Spellman
    • , Christopher Benz
    • , Daniel Carlin
    • , Melisssa Cline
    • , Brian Craft
    • , Kyle Ellrott
    • , Mary Goldman
    • , David Haussler
    • , Singer Ma
    • , Sam Ng
    • , Evan Paull
    • , Amie Radenbaugh
    • , Sofie Salama
    • , Artem Sokolov
    • , Joshua M Stuart
    • , Teresa Swatloski
    • , Vladislav Uzunangelov
    • , Peter Waltman
    • , Christina Yau
    • , Jing Zhu
    • , Stanley R Hamilton
    • , Gad Getz
    • , Carrie Sougnez
    • , Scott Abbott
    • , Rachel Abbott
    • , Nathan D Dees
    • , Kim Delehaunty
    • , Li Ding
    • , David J Dooling
    • , Jim M Eldred
    • , Catrina C Fronick
    • , Robert Fulton
    • , Lucinda L Fulton
    • , Joelle Kalicki-Veizer
    • , Krishna-Latha Kanchi
    • , Cyriac Kandoth
    • , Daniel C Koboldt
    • , David E Larson
    • , Timothy J Ley
    • , Ling Lin
    • , Charles Lu
    • , Vincent J Magrini
    • , Elaine R Mardis
    • , Michael D McLellan
    • , Joshua F McMichael
    • , Christopher A Miller
    • , Michelle O'Laughlin
    • , Craig Pohl
    • , Heather Schmidt
    • , Scott M Smith
    • , Jason Walker
    • , John W Wallis
    • , Michael C Wendl
    • , Richard K Wilson
    • , Todd Wylie
    • , Qunyuan Zhang
    • , Robert Burton
    • , Mark A Jensen
    • , Ari Kahn
    • , Todd Pihl
    • , David Pot
    • , Yunhu Wan
    • , Douglas A Levine
    • , Aaron D Black
    • , Jay Bowen
    • , Jessica Frick
    • , Julie M Gastier-Foster
    • , Hollie A Harper
    • , Carmen Helsel
    • , Kristen M Leraas
    • , Tara M Lichtenberg
    • , Cynthia McAllister
    • , Nilsa C Ramirez
    • , Samantha Sharpe
    • , Lisa Wise
    • , Erik Zmuda
    • , Stephen J Chanock
    • , Tanja Davidsen
    • , John A Demchok
    • , Greg Eley
    • , Ina Felau
    • , Brad A Ozenberger
    • , Margi Sheth
    • , Heidi Sofia
    • , Louis Staudt
    • , Roy Tarnuzzer
    • , Zhining Wang
    • , Liming Yang
    • , Jiashan Zhang
    • , Larsson Omberg
    • , Adam Margolin
    • , Benjamin J Raphael
    • , Fabio Vandin
    • , Hsin-Ta Wu
    • , Mark D M Leiserson
    • , Stephen C Benz
    • , Charles J Vaske
    • , Houtan Noushmehr
    • , Theo Knijnenburg
    • , Denise Wolf
    • , Laura Van't Veer
    • , Eric A Collisson
    • , Dimitris Anastassiou
    • , Tai-Hsien Ou Yang
    • , Nuria Lopez-Bigas
    • , Abel Gonzalez-Perez
    • , David Tamborero
    • , Zheng Xia
    • , Wei Li
    • , Dong-Yeon Cho
    • , Teresa Przytycka
    • , Mark Hamilton
    • , Sean McGuire
    • , Sven Nelander
    • , Patrik Johansson
    • , Rebecka Jörnsten
    • , Teresia Kling
    • , Jose Sanchez
    • , John N Weinstein
    • , Eric A Collisson
    • , Gordon B Mills
    • , Kenna R Mills Shaw
    • , Brad A Ozenberger
    • , Kyle Ellrott
    • , Ilya Shmulevich
    • , Chris Sander
    •  & Joshua M Stuart
  • Commentary
    | Open Access

    Larsson Omberg and colleagues write a Commentary describing the collaborative model used by the Pan-Cancer Working Group of The Cancer Genome Atlas. Pan-Cancer members used the Synapse software platform to share and evolve data, results and methods to perform integrative analyses of genome-wide molecular data for 12 cancer types.

    • Larsson Omberg
    • , Kyle Ellrott
    • , Yuan Yuan
    • , Cyriac Kandoth
    • , Chris Wong
    • , Michael R Kellen
    • , Stephen H Friend
    • , Josh Stuart
    • , Han Liang
    •  & Adam A Margolin
  • Commentary
    | Open Access

    • John Lonsdale
    • , Jeffrey Thomas
    • , Mike Salvatore
    • , Rebecca Phillips
    • , Edmund Lo
    • , Saboor Shad
    • , Richard Hasz
    • , Gary Walters
    • , Fernando Garcia
    • , Nancy Young
    • , Barbara Foster
    • , Mike Moser
    • , Ellen Karasik
    • , Bryan Gillard
    • , Kimberley Ramsey
    • , Susan Sullivan
    • , Jason Bridge
    • , Harold Magazine
    • , John Syron
    • , Johnelle Fleming
    • , Laura Siminoff
    • , Heather Traino
    • , Maghboeba Mosavel
    • , Laura Barker
    • , Scott Jewell
    • , Dan Rohrer
    • , Dan Maxim
    • , Dana Filkins
    • , Philip Harbach
    • , Eddie Cortadillo
    • , Bree Berghuis
    • , Lisa Turner
    • , Eric Hudson
    • , Kristin Feenstra
    • , Leslie Sobin
    • , James Robb
    • , Phillip Branton
    • , Greg Korzeniewski
    • , Charles Shive
    • , David Tabor
    • , Liqun Qi
    • , Kevin Groch
    • , Sreenath Nampally
    • , Steve Buia
    • , Angela Zimmerman
    • , Anna Smith
    • , Robin Burges
    • , Karna Robinson
    • , Kim Valentino
    • , Deborah Bradbury
    • , Mark Cosentino
    • , Norma Diaz-Mayoral
    • , Mary Kennedy
    • , Theresa Engel
    • , Penelope Williams
    • , Kenyon Erickson
    • , Kristin Ardlie
    • , Wendy Winckler
    • , Gad Getz
    • , David DeLuca
    • , Daniel MacArthur
    • , Manolis Kellis
    • , Alexander Thomson
    • , Taylor Young
    • , Ellen Gelfand
    • , Molly Donovan
    • , Yan Meng
    • , George Grant
    • , Deborah Mash
    • , Yvonne Marcus
    • , Margaret Basile
    • , Jun Liu
    • , Jun Zhu
    • , Zhidong Tu
    • , Nancy J Cox
    • , Dan L Nicolae
    • , Eric R Gamazon
    • , Hae Kyung Im
    • , Anuar Konkashbaev
    • , Jonathan Pritchard
    • , Matthew Stevens
    • , Timothèe Flutre
    • , Xiaoquan Wen
    • , Emmanouil T Dermitzakis
    • , Tuuli Lappalainen
    • , Roderic Guigo
    • , Jean Monlong
    • , Michael Sammeth
    • , Daphne Koller
    • , Alexis Battle
    • , Sara Mostafavi
    • , Mark McCarthy
    • , Manual Rivas
    • , Julian Maller
    • , Ivan Rusyn
    • , Andrew Nobel
    • , Fred Wright
    • , Andrey Shabalin
    • , Mike Feolo
    • , Nataliya Sharopova
    • , Anne Sturcke
    • , Justin Paschal
    • , James M Anderson
    • , Elizabeth L Wilder
    • , Leslie K Derr
    • , Eric D Green
    • , Jeffery P Struewing
    • , Gary Temple
    • , Simona Volpi
    • , Joy T Boyer
    • , Elizabeth J Thomson
    • , Mark S Guyer
    • , Cathy Ng
    • , Assya Abdallah
    • , Deborah Colantuoni
    • , Thomas R Insel
    • , Susan E Koester
    • , A Roger Little
    • , Patrick K Bender
    • , Thomas Lehner
    • , Yin Yao
    • , Carolyn C Compton
    • , Jimmie B Vaught
    • , Sherilyn Sawyer
    • , Nicole C Lockhart
    • , Joanne Demchok
    •  & Helen F Moore
  • Commentary
    | Open Access

    • Susanna-Assunta Sansone
    • , Philippe Rocca-Serra
    • , Dawn Field
    • , Eamonn Maguire
    • , Chris Taylor
    • , Oliver Hofmann
    • , Hong Fang
    • , Steffen Neumann
    • , Weida Tong
    • , Linda Amaral-Zettler
    • , Kimberly Begley
    • , Tim Booth
    • , Lydie Bougueleret
    • , Gully Burns
    • , Brad Chapman
    • , Tim Clark
    • , Lee-Ann Coleman
    • , Jay Copeland
    • , Sudeshna Das
    • , Antoine de Daruvar
    • , Paula de Matos
    • , Ian Dix
    • , Scott Edmunds
    • , Chris T Evelo
    • , Mark J Forster
    • , Pascale Gaudet
    • , Jack Gilbert
    • , Carole Goble
    • , Julian L Griffin
    • , Daniel Jacob
    • , Jos Kleinjans
    • , Lee Harland
    • , Kenneth Haug
    • , Henning Hermjakob
    • , Shannan J Ho Sui
    • , Alain Laederach
    • , Shaoguang Liang
    • , Stephen Marshall
    • , Annette McGrath
    • , Emily Merrill
    • , Dorothy Reilly
    • , Magali Roux
    • , Caroline E Shamu
    • , Catherine A Shang
    • , Christoph Steinbeck
    • , Anne Trefethen
    • , Bryn Williams-Jones
    • , Katherine Wolstencroft
    • , Ioannis Xenarios
    •  & Winston Hide
  • Commentary |

    • Barend Mons
    • , Herman van Haagen
    • , Christine Chichester
    • , Peter-Bram 't Hoen
    • , Johan T den Dunnen
    • , Gertjan van Ommen
    • , Erik van Mulligen
    • , Bharat Singh
    • , Rob Hooft
    • , Marco Roos
    • , Joel Hammond
    • , Bruce Kiesel
    • , Belinda Giardine
    • , Jan Velterop
    • , Paul Groth
    •  & Erik Schultes
  • Commentary |

    Colleen McBride and colleagues argue that progress on a multifaceted research agenda is necessary to reap the full benefits and avoid the potential pitfalls of the emerging area of personalized genomics. They also outline one element of this agenda, the Multiplex Initiative, which has been underway since 2006.

    • Colleen M McBride
    • , Sharon Hensley Alford
    • , Robert J Reid
    • , Eric B Larson
    • , Andreas D Baxevanis
    •  & Lawrence C Brody
  • Commentary |

    It has been four years since the original publication of the draft sequence of the rat genome. Five groups are now working together to assemble, annotate and release an updated version of the rat genome. As the prevailing model for physiology, complex disease and pharmacological studies, there is an acute need for the rat's genomic resources to keep pace with the rat's prominence in the laboratory. In this commentary, we describe the current status of the rat genome sequence and the plans for its impending 'upgrade'. We then cover the key online resources providing access to the rat genome, including the new SNP views at Ensembl, the RefSeq and Genes databases at the US National Center for Biotechnology Information, Genome Browser at the University of California Santa Cruz and the disease portals for cardiovascular disease and obesity at the Rat Genome Database.

    • Simon N Twigger
    • , Kim D Pruitt
    • , Xosé M Fernández-Suárez
    • , Donna Karolchik
    • , Kim C Worley
    • , Donna R Maglott
    • , Garth Brown
    • , George Weinstock
    • , Richard A Gibbs
    • , Jim Kent
    • , Ewan Birney
    •  & Howard J Jacob
  • Commentary |

    Medical genetics involves the application of genetic knowledge and technology to specific clinical and epidemiologic concerns. Using genetics to benefit society requires that empirically verified knowledge be used within an ethical framework that combines appeal to written precedent with sensitivity to the options of individuals and families dealing with choices and necessities within the laws, norms and traditions of their society. Islamic bioethics is derived from a combination of principles, duties and rights, and to a certain extent a call to virtue, ihsan. It emphasizes prevention, and it teaches that the patient must be treated with respect and compassion and that the physical, mental and spiritual dimensions of the illness experience must be taken into account. Strategic planning for the prevention and care of genetic disorders, and for genomic research, within the context of Islamic religion and culture is promising and may provide lessons to the developed world. Islamic bioethics provides fundamental principles for genetic counseling, particularly in regard to consanguinity, which was part of the Arabian culture long before Islam but which was discouraged by the second Islamic khalifa. These fundamental principles are important for implementing many preventive and genomic research programs and for maintaining flexibility to respond to new biomedical technologies.

    • Aida I Al Aqeel
  • Commentary |

    The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data.

    • Matthew D Mailman
    • , Michael Feolo
    • , Yumi Jin
    • , Masato Kimura
    • , Kimberly Tryka
    • , Rinat Bagoutdinov
    • , Luning Hao
    • , Anne Kiang
    • , Justin Paschall
    • , Lon Phan
    • , Natalia Popova
    • , Stephanie Pretel
    • , Lora Ziyabari
    • , Moira Lee
    • , Yu Shao
    • , Zhen Y Wang
    • , Karl Sirotkin
    • , Minghong Ward
    • , Michael Kholodov
    • , Kerry Zbicz
    • , Jeffrey Beck
    • , Michael Kimelman
    • , Sergey Shevelev
    • , Don Preuss
    • , Eugene Yaschenko
    • , Alan Graeff
    • , James Ostell
    •  & Stephen T Sherry
  • Commentary |

    The Genetic Association Information Network (GAIN) is a public-private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases.

    • Teri A Manolio
    • , Laura Lyman Rodriguez
    • , Lisa Brooks
    • , Gonçalo Abecasis
    • , Dennis Ballinger
    • , Mark Daly
    • , Peter Donnelly
    • , Stephen V Faraone
    • , Kelly Frazer
    • , Stacey Gabriel
    • , Pablo Gejman
    • , Alan Guttmacher
    • , Emily L Harris
    • , Thomas Insel
    • , John R Kelsoe
    • , Eric Lander
    • , Norma McCowin
    • , Matthew D Mailman
    • , Elizabeth Nabel
    • , James Ostell
    • , Elizabeth Pugh
    • , Stephen Sherry
    • , Patrick F Sullivan
    • , John F Thompson
    • , James Warram
    • , David Wholley
    • , Patrice M Milos
    •  & Francis S Collins
  • Commentary |

    Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization–cosponsored meeting on June 20–23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations.

    • Richard G.H. Cotton
    • , William Appelbe
    • , Arleen D Auerbach
    • , Kevin Becker
    • , Walter Bodmer
    • , D Joe Boone
    • , Victor Boulyjenkov
    • , Samir Brahmachari
    • , Lawrence Brody
    • , Anthony Brookes
    • , Alastair F Brown
    • , Peter Byers
    • , Jose Maria Cantu
    • , Jean-Jacques Cassiman
    • , Mireille Claustres
    • , Patrick Concannon
    • , Richard G H Cotton
    • , Johan T den Dunnen
    • , Paul Flicek
    • , Richard Gibbs
    • , Judith Hall
    • , Julia Hasler
    • , Michael Katz
    • , Pui-Yan Kwok
    • , Sandrine Laradi
    • , Annika Lindblom
    • , Donna Maglott
    • , Steven Marsh
    • , Collen Muto Masimirembwa
    • , Shinsei Minoshima
    • , Ana Maria Oller de Ramirez
    • , Roberta Pagon
    • , Raj Ramesar
    • , David Ravine
    • , Sue Richards
    • , David Rimoin
    • , Huijun Z Ring
    • , Charles R Scriver
    • , Stephen Sherry
    • , Nobuyoshi Shimizu
    • , Lincoln Stein
    • , Ghazi Omar Tadmouri
    • , Graham Taylor
    •  & Michael Watson
  • Commentary |

    Recent experience with several high-profile drugs demonstrates the great challenges in developing effective and safe therapeutics. A complementary approach to the popular paradigm of disease genetics is based on inherited factors that reduce the incidence and severity of disease among individuals who are genetically predisposed to disease. We propose testing specifically for modifier genes and protective alleles among at-risk individuals and studying the efficacy of therapeutics based on the genetics of health.

    • Joseph H Nadeau
    •  & Eric J Topol
  • Commentary |

    Three very recent reports provide convincing statistical evidence (P < 10−8), at a genome-wide level, of the association of common polymorphisms with three different common diseases: systemic lupus erythematosus (IRF5), prostate cancer and type 1 diabetes (IFIH1 region). This adds to the trickle—soon to be a flood—of disease association results that are highly unlikely to be false positives. There are other convincing examples in the last 12 months: age-related macular degeneration (CFH), type 1 diabetes (IL2RA, also known as CD25) and type 2 diabetes (TCF7L2). Given 20 years of a literature full of irreproducible results, what has changed?

    • John A Todd
  • Commentary |

    Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.

    • John P A Ioannidis
    • , Marta Gwinn
    • , Julian Little
    • , Julian P T Higgins
    • , Jonine L Bernstein
    • , Paolo Boffetta
    • , Melissa Bondy
    • , Molly S Bray
    • , Paul E Brenchley
    • , Patricia A Buffler
    • , Juan Pablo Casas
    • , Anand Chokkalingam
    • , John Danesh
    • , George Davey Smith
    • , Siobhan Dolan
    • , Ross Duncan
    • , Nelleke A Gruis
    • , Patricia Hartge
    • , Mia Hashibe
    • , David J Hunter
    • , Marjo-Riitta Jarvelin
    • , Beatrice Malmer
    • , Demetrius M Maraganore
    • , Julia A Newton-Bishop
    • , Thomas R O'Brien
    • , Gloria Petersen
    • , Elio Riboli
    • , Georgia Salanti
    • , Daniela Seminara
    • , Liam Smeeth
    • , Emanuela Taioli
    • , Nic Timpson
    • , Andre G Uitterlinden
    • , Paolo Vineis
    • , Nick Wareham
    • , Deborah M Winn
    • , Ron Zimmern
    •  & Muin J Khoury
  • Commentary |

    The identification and investigation of sentinel cases has illuminated genetic discrimination in the US. Its occurrence impedes applications of biotechnology and is a primary focus of public policy activity at the federal level. Continued research and informed responses may make genetic nondiscrimination more likely.

    • Paul R Billings
  • Commentary |

    The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

    • Gary A Churchill
    • , David C Airey
    • , Hooman Allayee
    • , Joe M Angel
    • , Alan D Attie
    • , Jackson Beatty
    • , William D Beavis
    • , John K Belknap
    • , Beth Bennett
    • , Wade Berrettini
    • , Andre Bleich
    • , Molly Bogue
    • , Karl W Broman
    • , Kari J Buck
    • , Ed Buckler
    • , Margit Burmeister
    • , Elissa J Chesler
    • , James M Cheverud
    • , Steven Clapcote
    • , Melloni N Cook
    • , Roger D Cox
    • , John C Crabbe
    • , Wim E Crusio
    • , Ariel Darvasi
    • , Christian F Deschepper
    • , R W Doerge
    • , Charles R Farber
    • , Jiri Forejt
    • , Daniel Gaile
    • , Steven J Garlow
    • , Hartmut Geiger
    • , Howard Gershenfeld
    • , Terry Gordon
    • , Jing Gu
    • , Weikuan Gu
    • , Gerald de Haan
    • , Nancy L Hayes
    • , Craig Heller
    • , Heinz Himmelbauer
    • , Robert Hitzemann
    • , Kent Hunter
    • , Hui-Chen Hsu
    • , Fuad A Iraqi
    • , Boris Ivandic
    • , Howard J Jacob
    • , Ritsert C Jansen
    • , Karl J Jepsen
    • , Dabney K Johnson
    • , Thomas E Johnson
    • , Gerd Kempermann
    • , Christina Kendziorski
    • , Malak Kotb
    • , R Frank Kooy
    • , Bastien Llamas
    • , Frank Lammert
    • , Jean-Michel Lassalle
    • , Pedro R Lowenstein
    • , Lu Lu
    • , Aldons Lusis
    • , Kenneth F Manly
    • , Ralph Marcucio
    • , Doug Matthews
    • , Juan F Medrano
    • , Darla R Miller
    • , Guy Mittleman
    • , Beverly A Mock
    • , Jeffrey S Mogil
    • , Xavier Montagutelli
    • , Grant Morahan
    • , David G Morris
    • , Richard Mott
    • , Joseph H Nadeau
    • , Hiroki Nagase
    • , Richard S Nowakowski
    • , Bruce F O'Hara
    • , Alexander V Osadchuk
    • , Grier P Page
    • , Beverly Paigen
    • , Kenneth Paigen
    • , Abraham A Palmer
    • , Huei-Ju Pan
    • , Leena Peltonen-Palotie
    • , Jeremy Peirce
    • , Daniel Pomp
    • , Michal Pravenec
    • , Daniel R Prows
    • , Zhonghua Qi
    • , Roger H Reeves
    • , John Roder
    • , Glenn D Rosen
    • , Eric E Schadt
    • , Leonard C Schalkwyk
    • , Ze'ev Seltzer
    • , Kazuhiro Shimomura
    • , Siming Shou
    • , Mikko J. Sillanpää
    • , Linda D Siracusa
    • , Hans-Willem Snoeck
    • , Jimmy L Spearow
    • , Karen Svenson
    • , Lisa M Tarantino
    • , David Threadgill
    • , Linda A Toth
    • , William Valdar
    • , Fernando Pardo-Manuel de Villena
    • , Craig Warden
    • , Steve Whatley
    • , Robert W Williams
    • , Tim Wiltshire
    • , Nengjun Yi
    • , Dabao Zhang
    • , Min Zhang
    •  & Fei Zou
  • Commentary |

    Data on human genetic variation help scientists to understand human origins, susceptibility to illness and genetic causes of disease. Destructive episodes in the history of genetic research make it crucial to consider the ethical and social implications of research in genomics, especially human genetic variation. The analysis of ethical, legal and social implications should be integrated into genetic research, with the participation of scientists who can anticipate and monitor the full range of possible applications of the research from the earliest stages. The design and implementation of research directs the ways in which its results can be used, and data and technology, rather than ethical considerations or social needs, drive the use of science in unintended ways. Here we examine forensic genetics and argue that all geneticists should anticipate the ethical and social issues associated with nonmedical applications of genetic variation research.

    • Mildred K Cho
    •  & Pamela Sankar
  • Commentary |

    A true understanding of disease risk requires a thorough examination of root causes. 'Race' and 'ethnicity' are poorly defined terms that serve as flawed surrogates for multiple environmental and genetic factors in disease causation, including ancestral geographic origins, socioeconomic status, education and access to health care. Research must move beyond these weak and imperfect proxy relationships to define the more proximate factors that influence health.

    • Francis S Collins
  • Commentary |

    Knowledge from the Human Genome Project and research on human genome variation increasingly challenges the applicability of the term 'race' to human population groups, raising questions about the validity of inferences made about 'race' in the biomedical and scientific literature. Despite the acknowledged contradictions in contemporary science, population-based genetic variation is continually used to explain differences in health between 'racial' and 'ethnic' groups. In this commentary we posit that resolution of apparent paradoxes in relating biology to 'race' and genetics requires thinking 'outside of the box'.

    • Charmaine D M Royal
    •  & Georgia M Dunston
  • Commentary |

    Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.

    • Christopher P Austin
    • , James F Battey
    • , Allan Bradley
    • , Maja Bucan
    • , Mario Capecchi
    • , Francis S Collins
    • , William F Dove
    • , Geoffrey Duyk
    • , Susan Dymecki
    • , Janan T Eppig
    • , Franziska B Grieder
    • , Nathaniel Heintz
    • , Geoff Hicks
    • , Thomas R Insel
    • , Alexandra Joyner
    • , Beverly H Koller
    • , K C Kent Lloyd
    • , Terry Magnuson
    • , Mark W Moore
    • , Andras Nagy
    • , Jonathan D Pollock
    • , Allen D Roses
    • , Arthur T Sands
    • , Brian Seed
    • , William C Skarnes
    • , Jay Snoddy
    • , Philippe Soriano
    • , David J Stewart
    • , Francis Stewart
    • , Bruce Stillman
    • , Harold Varmus
    • , Lyuba Varticovski
    • , Inder M Verma
    • , Thomas F Vogt
    • , Harald von Melchner
    • , Jan Witkowski
    • , Richard P Woychik
    • , Wolfgang Wurst
    • , George D Yancopoulos
    • , Stephen G Young
    •  & Brian Zambrowicz
  • Commentary |

    The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.

    • Johan Auwerx
    • , Phil Avner
    • , Richard Baldock
    • , Andrea Ballabio
    • , Rudi Balling
    • , Mariano Barbacid
    • , Anton Berns
    • , Allan Bradley
    • , Steve Brown
    • , Peter Carmeliet
    • , Pierre Chambon
    • , Roger Cox
    • , Duncan Davidson
    • , Kay Davies
    • , Denis Duboule
    • , Jiri Forejt
    • , Francesca Granucci
    • , Nick Hastie
    • , Martin Hrabé de Angelis
    • , Ian Jackson
    • , Dimitris Kioussis
    • , George Kollias
    • , Mark Lathrop
    • , Urban Lendahl
    • , Marcos Malumbres
    • , Harald von Melchner
    • , Werner Müller
    • , Juha Partanen
    • , Paola Ricciardi-Castagnoli
    • , Peter Rigby
    • , Barry Rosen
    • , Nadia Rosenthal
    • , Bill Skarnes
    • , A Francis Stewart
    • , Janet Thornton
    • , Glauco Tocchini-Valentini
    • , Erwin Wagner
    • , Walter Wahli
    •  & Wolfgang Wurst
  • Commentary |

    Genomic profiling has the potential to usher in a revolution of personalized healthcare and disease prevention. But evidence to support genomic profiling is inconsistent, and data on the health outcome benefits based on such testing are lacking. For genomic profiling to become valid and useful, well designed epidemiologic studies and thorough clinical evaluations of recommended interventions based on genotype are required.

    • Susanne B Haga
    • , Muin J Khoury
    •  & Wylie Burke
  • Commentary |

    A principal goal of genetic research is to identify specific genotypes that are associated with human phenotypes. It will soon be possible to conduct genome-wide genotyping on a massive scale. Our current approaches for defining and assaying phenotypes may be inadequate for making optimal use of such genotypic data. We propose an international effort to create phenomic databases, that is, comprehensive assemblages of systematically collected phenotypic information, and to develop new approaches for analyzing such phenotypic data. We term this effort the Human Phenome Project and suggest a scientific and organizational scope for the project.

    • Nelson Freimer
    •  & Chiara Sabatti
  • Commentary |

    We would like to be able to predict how genomes are folded in the cell from the primary DNA sequence. A model for the three-dimensional structure of all genomes is presented; it is based on the structure of the bacterial nucleoid, where RNA polymerases cluster and loop the DNA. Loops appear and disappear as polymerases initiate and terminate, but the microscopic structure is 'self-organizing' and, to some extent, predictable. At the macroscopic level, transcriptional activity drives pairing between homologous sequences, inactivity allows genome compaction, and the segregation machinery orients whole chromosomes.

    • Peter R. Cook
  • Commentary |

    • Alvis Brazma
    • , Pascal Hingamp
    • , John Quackenbush
    • , Gavin Sherlock
    • , Paul Spellman
    • , Chris Stoeckert
    • , John Aach
    • , Wilhelm Ansorge
    • , Catherine A. Ball
    • , Helen C. Causton
    • , Terry Gaasterland
    • , Patrick Glenisson
    • , Frank C.P. Holstege
    • , Irene F. Kim
    • , Victor Markowitz
    • , John C. Matese
    • , Helen Parkinson
    • , Alan Robinson
    • , Ugis Sarkans
    • , Steffen Schulze-Kremer
    • , Jason Stewart
    • , Ronald Taylor
    • , Jaak Vilo
    •  & Martin Vingron
  • Commentary |

    There is an increasing concern within both the scientific and security communities that the ongoing revolution in biology has great potential to be misused in offensive biological weapons programs. In light of the 11 September tragedy, we can no longer afford to be complacent about the possibility of biological terrorism. Here we review the major relevant trends in genomics research and development, and discuss how these capabilities might be misused in the design of new bioweapons. We also discuss how the breakthroughs that have come from the genomics revolution may be used to enhance detection, protection and treatment so that biological warfare agents are never used.

    • Claire M. Fraser
    •  & Malcolm R. Dando
  • Commentary |

    The clinical use of pharmacogenetic drugs will require that a sample of a patient's DNA be tested before a drug is prescribed. Although pharmacogenetic tests pose fewer risks than genetic tests for disease mutations, they might still reveal personal information that could be used adversely to a patient's interests. Informed consent and privacy of pharmacogenetic test results may be essential in most clinical uses of pharmacogenetic drugs.

    • John A. Robertson
  • Commentary |

    “They all talked at once, their voices insistent and contradictory and impatient, making of unreality a possibility, then a probability, then an incontrovertible fact, as people will when their desires become words.” —W. Faulkner, The Sound and the Fury, 1929

    • Kenneth M. Weiss
    •  & Joseph D. Terwilliger
  • Commentary |

    In model organisms, chemical mutagenesis provides a powerful alternative to natural, polygenic variation (for example, quantitative trait loci (QTLs)) for identifying functional pathways and complex disease genes. Despite recent progress in QTLs, we expect that mutagenesis will ultimately prove more effective because the prospects of gene identification are high and every gene affecting a trait is potentially a target.

    • Joseph H. Nadeau
    •  & Wayne N. Frankel
  • Commentary |

    Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web ( http://www.geneontology.org ) are being constructed: biological process, molecular function and cellular component.

    • Michael Ashburner
    • , Catherine A. Ball
    • , Judith A. Blake
    • , David Botstein
    • , Heather Butler
    • , J. Michael Cherry
    • , Allan P. Davis
    • , Kara Dolinski
    • , Selina S. Dwight
    • , Janan T. Eppig
    • , Midori A. Harris
    • , David P. Hill
    • , Laurie Issel-Tarver
    • , Andrew Kasarskis
    • , Suzanna Lewis
    • , John C. Matese
    • , Joel E. Richardson
    • , Martin Ringwald
    • , Gerald M. Rubin
    •  & Gavin Sherlock
  • Commentary |

    • Jon A. Beck
    • , Sarah Lloyd
    • , Majid Hafezparast
    • , Moyha Lennon-Pierce
    • , Janan T. Eppig
    • , Michael F.W. Festing
    •  & Elizabeth M.C. Fisher