Volume 43 Issue 3, March 2011

Volume 43 Issue 3

Cover art by Lewis Long

Editorial

  • Editorial |

    The substantial $10 million purse of the Archon Genomics X PRIZE (AGXP) is being offered for the generation of rapid, accurate and complete human DNA sequences. Because so many genomics researchers have a stake, we offer to help with a process of community consultation to help evolve fair and efficient methods to validate contestant data for the competition.

Correspondence

News and Views

  • News & Views |

    Expression of oncogenes in otherwise normal cells often leads to the activation of anti-oncogenic pathways through a poorly understood process described as 'oncogenic stress'. A new study implicates the Jnk pathway signaling in the activation of p53 in response to both K-Ras and Neu oncogene expression.

    • Kevin M Haigis
    •  & Alejandro Sweet-Cordero
  • News & Views |

    A new study uses genome-wide SNP genotypes to identify a subset of children undergoing therapy for acute lymphoblastic leukemia that are at increased risk for relapse. Borrowing from the classical approach of admixture mapping, the work shows how genome-wide assessment of genetic ancestry can be used as a biomarker for disease outcome.

    • Stephen J Chanock
  • News & Views |

    Follow-up studies of a Crohn's disease risk locus encompassing IRGM have revealed unexpected complexity. A new study shows that a synonymous variant in the IRGM coding region alters a binding site for miR-196 and modulates IRGM-dependent autophagy, adding to the list of possible mechanisms by which this locus influences disease risk.

    • Michel Georges

Research Highlights

Brief Communication

  • Brief Communication |

    Rulla Tamimi and colleagues report a meta-analysis of five genome-wide association studies for percent mammographic density. They identify an associated locus at ZNF365, which has also been associated with susceptibility to breast cancer.

    • Sara Lindström
    • , Celine M Vachon
    • , Jingmei Li
    • , Jajini Varghese
    • , Deborah Thompson
    • , Ruth Warren
    • , Judith Brown
    • , Jean Leyland
    • , Tina Audley
    • , Nicholas J Wareham
    • , Ruth J F Loos
    • , Andrew D Paterson
    • , Johanna Rommens
    • , Darryl Waggott
    • , Lisa J Martin
    • , Christopher G Scott
    • , V Shane Pankratz
    • , Susan E Hankinson
    • , Aditi Hazra
    • , David J Hunter
    • , John L Hopper
    • , Melissa C Southey
    • , Stephen J Chanock
    • , Isabel dos Santos Silva
    • , JianJun Liu
    • , Louise Eriksson
    • , Fergus J Couch
    • , Jennifer Stone
    • , Carmel Apicella
    • , Kamila Czene
    • , Peter Kraft
    • , Per Hall
    • , Douglas F Easton
    • , Norman F Boyd
    •  & Rulla M Tamimi

Articles

  • Article |

    Nicholas Katsanis and colleagues show that biallelic mutations in TTC21B, encoding the retrograde intraflagellar transport protein IFT139, are associated with diverse ciliopathy phenotypes in humans. They further show that pathogenic alleles of TTC21B are present in as many as 5% of ciliopathy cases, supporting an oligogenic model of disease.

    • Erica E Davis
    • , Qi Zhang
    • , Qin Liu
    • , Bill H Diplas
    • , Lisa M Davey
    • , Jane Hartley
    • , Corinne Stoetzel
    • , Katarzyna Szymanska
    • , Gokul Ramaswami
    • , Clare V Logan
    • , Donna M Muzny
    • , Alice C Young
    • , David A Wheeler
    • , Pedro Cruz
    • , Margaret Morgan
    • , Lora R Lewis
    • , Praveen Cherukuri
    • , Baishali Maskeri
    • , Nancy F Hansen
    • , James C Mullikin
    • , Robert W Blakesley
    • , Gerard G Bouffard
    • , NISC Comparative Sequencing Program
    • , Gabor Gyapay
    • , Susanne Rieger
    • , Burkhard Tönshoff
    • , Ilse Kern
    • , Neveen A Soliman
    • , Thomas J Neuhaus
    • , Kathryn J Swoboda
    • , Hulya Kayserili
    • , Tomas E Gallagher
    • , Richard A Lewis
    • , Carsten Bergmann
    • , Edgar A Otto
    • , Sophie Saunier
    • , Peter J Scambler
    • , Philip L Beales
    • , Joseph G Gleeson
    • , Eamonn R Maher
    • , Tania Attié-Bitach
    • , Hélène Dollfus
    • , Colin A Johnson
    • , Eric D Green
    • , Richard A Gibbs
    • , Friedhelm Hildebrandt
    • , Eric A Pierce
    •  & Nicholas Katsanis
  • Article |

    Phil Beales and colleagues show that mutations in the lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome, a disorder that includes craniofacial defects, learning disability and other developmental phenotypes. They also present evidence that the COLEC11 gene product serves as a guidance cue for neural crest cell migration.

    • Caroline Rooryck
    • , Anna Diaz-Font
    • , Daniel P S Osborn
    • , Elyes Chabchoub
    • , Victor Hernandez-Hernandez
    • , Hanan Shamseldin
    • , Joanna Kenny
    • , Aoife Waters
    • , Dagan Jenkins
    • , Ali Al Kaissi
    • , Gabriela F Leal
    • , Bruno Dallapiccola
    • , Franco Carnevale
    • , Maria Bitner-Glindzicz
    • , Melissa Lees
    • , Raoul Hennekam
    • , Philip Stanier
    • , Alan J Burns
    • , Hilde Peeters
    • , Fowzan S Alkuraya
    •  & Philip L Beales
  • Article |

    Josef Penninger and colleagues show that deletion of the stress kinase MKK7 in mouse models of lung and mammary tumors accelerates tumor onset and reduces overall survival. The study suggests that MKK7 is a sensor of oncogenic stress.

    • Daniel Schramek
    • , Athanassios Kotsinas
    • , Arabella Meixner
    • , Teiji Wada
    • , Ulrich Elling
    • , J Andrew Pospisilik
    • , G Gregory Neely
    • , Ralf-Harun Zwick
    • , Verena Sigl
    • , Guido Forni
    • , Manuel Serrano
    • , Vassilis G Gorgoulis
    •  & Josef M Penninger
  • Article |

    Geneviève Almouzni and colleagues report that SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin in mouse. They identify long nuclear non-coding transcripts at major satellite repeats and show that they specifically associate with SUMO-modified HP1 proteins.

    • Christèle Maison
    • , Delphine Bailly
    • , Danièle Roche
    • , Rocio Montes de Oca
    • , Aline V Probst
    • , Isabelle Vassias
    • , Florent Dingli
    • , Bérengère Lombard
    • , Damarys Loew
    • , Jean-Pierre Quivy
    •  & Geneviève Almouzni
  • Article | | open

    Richard Wilson and colleagues report the genome sequence of Trichinella spiralis, a food-borne parasitic nematode that diverged early in the evolution of the phylum Nematoda. T. spiralis is the most common cause of human trichinellosis.

    • Makedonka Mitreva
    • , Douglas P Jasmer
    • , Dante S Zarlenga
    • , Zhengyuan Wang
    • , Sahar Abubucker
    • , John Martin
    • , Christina M Taylor
    • , Yong Yin
    • , Lucinda Fulton
    • , Pat Minx
    • , Shiaw-Pyng Yang
    • , Wesley C Warren
    • , Robert S Fulton
    • , Veena Bhonagiri
    • , Xu Zhang
    • , Kym Hallsworth-Pepin
    • , Sandra W Clifton
    • , James P McCarter
    • , Judith Appleton
    • , Elaine R Mardis
    •  & Richard K Wilson

Letters

  • Letter |

    Mary Relling and colleagues explore the effects of ancestry on the pharmacogenomics of relapse in acute lymphoblastic leukemia. They found that Native American ancestry was associated with risk of relapse but that differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy.

    • Jun J Yang
    • , Cheng Cheng
    • , Meenakshi Devidas
    • , Xueyuan Cao
    • , Yiping Fan
    • , Dario Campana
    • , Wenjian Yang
    • , Geoff Neale
    • , Nancy J Cox
    • , Paul Scheet
    • , Michael J Borowitz
    • , Naomi J Winick
    • , Paul L Martin
    • , Cheryl L Willman
    • , W Paul Bowman
    • , Bruce M Camitta
    • , Andrew Carroll
    • , Gregory H Reaman
    • , William L Carroll
    • , Mignon Loh
    • , Stephen P Hunger
    • , Ching-Hon Pui
    • , William E Evans
    •  & Mary V Relling
  • Letter |

    Paul Hofman and colleagues show that a synonymous variant in IRGM, previously associated with risk of Crohn's disease, alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy. These findings implicate this synonymous polymorphism as a likely causal variant underlying the association of IRGM with Crohn's disease.

    • Patrick Brest
    • , Pierre Lapaquette
    • , Mouloud Souidi
    • , Kevin Lebrigand
    • , Annabelle Cesaro
    • , Valérie Vouret-Craviari
    • , Bernard Mari
    • , Pascal Barbry
    • , Jean-François Mosnier
    • , Xavier Hébuterne
    • , Annick Harel-Bellan
    • , Baharia Mograbi
    • , Arlette Darfeuille-Michaud
    •  & Paul Hofman
  • Letter |

    John Rioux and colleagues report results of a large genome-wide association meta-analysis and follow-up study of ulcerative colitis. They identify 29 new risk loci for this inflammatory disease and show that many risk loci are shared between ulcerative colitis and Crohn's disease.

    • Carl A Anderson
    • , Gabrielle Boucher
    • , Charlie W Lees
    • , Andre Franke
    • , Mauro D'Amato
    • , Kent D Taylor
    • , James C Lee
    • , Philippe Goyette
    • , Marcin Imielinski
    • , Anna Latiano
    • , Caroline Lagacé
    • , Regan Scott
    • , Leila Amininejad
    • , Suzannah Bumpstead
    • , Leonard Baidoo
    • , Robert N Baldassano
    • , Murray Barclay
    • , Theodore M Bayless
    • , Stephan Brand
    • , Carsten Büning
    • , Jean-Frédéric Colombel
    • , Lee A Denson
    • , Martine De Vos
    • , Marla Dubinsky
    • , Cathryn Edwards
    • , David Ellinghaus
    • , Rudolf S N Fehrmann
    • , James A B Floyd
    • , Timothy Florin
    • , Denis Franchimont
    • , Lude Franke
    • , Michel Georges
    • , Jürgen Glas
    • , Nicole L Glazer
    • , Stephen L Guthery
    • , Talin Haritunians
    • , Nicholas K Hayward
    • , Jean-Pierre Hugot
    • , Gilles Jobin
    • , Debby Laukens
    • , Ian Lawrance
    • , Marc Lémann
    • , Arie Levine
    • , Cecile Libioulle
    • , Edouard Louis
    • , Dermot P McGovern
    • , Monica Milla
    • , Grant W Montgomery
    • , Katherine I Morley
    • , Craig Mowat
    • , Aylwin Ng
    • , William Newman
    • , Roel A Ophoff
    • , Laura Papi
    • , Orazio Palmieri
    • , Laurent Peyrin-Biroulet
    • , Julián Panés
    • , Anne Phillips
    • , Natalie J Prescott
    • , Deborah D Proctor
    • , Rebecca Roberts
    • , Richard Russell
    • , Paul Rutgeerts
    • , Jeremy Sanderson
    • , Miquel Sans
    • , Philip Schumm
    • , Frank Seibold
    • , Yashoda Sharma
    • , Lisa A Simms
    • , Mark Seielstad
    • , A Hillary Steinhart
    • , Stephan R Targan
    • , Leonard H van den Berg
    • , Morten Vatn
    • , Hein Verspaget
    • , Thomas Walters
    • , Cisca Wijmenga
    • , David C Wilson
    • , Harm-Jan Westra
    • , Ramnik J Xavier
    • , Zhen Z Zhao
    • , Cyriel Y Ponsioen
    • , Vibeke Andersen
    • , Leif Torkvist
    • , Maria Gazouli
    • , Nicholas P Anagnou
    • , Tom H Karlsen
    • , Limas Kupcinskas
    • , Jurgita Sventoraityte
    • , John C Mansfield
    • , Subra Kugathasan
    • , Mark S Silverberg
    • , Jonas Halfvarson
    • , Jerome I Rotter
    • , Christopher G Mathew
    • , Anne M Griffiths
    • , Richard Gearry
    • , Tariq Ahmad
    • , Steven R Brant
    • , Mathias Chamaillard
    • , Jack Satsangi
    • , Judy H Cho
    • , Stefan Schreiber
    • , Mark J Daly
    • , Jeffrey C Barrett
    • , Miles Parkes
    • , Vito Annese
    • , Hakon Hakonarson
    • , Graham Radford-Smith
    • , Richard H Duerr
    • , Séverine Vermeire
    • , Rinse K Weersma
    •  & John D Rioux
  • Letter |

    Patrick Gaffney and colleagues perform a fine-mapping study of the TNFAIP3 region in systemic lupus erythematosus using individuals from diverse ancestral populations. They identify a putative causal variant in a region of high conservation and regulatory potential that is associated with reduced TNFAIP3 expression.

    • Indra Adrianto
    • , Feng Wen
    • , Amanda Templeton
    • , Graham Wiley
    • , Jarrod B King
    • , Christopher J Lessard
    • , Jared S Bates
    • , Yanqing Hu
    • , Jennifer A Kelly
    • , Kenneth M Kaufman
    • , Joel M Guthridge
    • , Marta E Alarcón-Riquelme
    • , Juan-Manuel Anaya
    • , Sang-Cheol Bae
    • , So-Young Bang
    • , Susan A Boackle
    • , Elizabeth E Brown
    • , Michelle A Petri
    • , Caroline Gallant
    • , Rosalind Ramsey-Goldman
    • , John D Reveille
    • , Luis M Vila
    • , Lindsey A Criswell
    • , Jeffrey C Edberg
    • , Barry I Freedman
    • , Peter K Gregersen
    • , Gary S Gilkeson
    • , Chaim O Jacob
    • , Judith A James
    • , Diane L Kamen
    • , Robert P Kimberly
    • , Javier Martin
    • , Joan T Merrill
    • , Timothy B Niewold
    • , So-Yeon Park
    • , Bernardo A Pons-Estel
    • , R Hal Scofield
    • , Anne M Stevens
    • , Betty P Tsao
    • , Timothy J Vyse
    • , Carl D Langefeld
    • , John B Harley
    • , Kathy L Moser
    • , Carol F Webb
    • , Mary Beth Humphrey
    • , Courtney Gray Montgomery
    •  & Patrick M Gaffney
  • Letter |

    Massimo Zeviani and colleagues report mutations in TTC19 cause mitochondrial defects and progressive encephalopathy in humans. Adult flies lacking TTC19 function also display signs of neurological impairment.

    • Daniele Ghezzi
    • , Paola Arzuffi
    • , Mauro Zordan
    • , Caterina Da Re
    • , Costanza Lamperti
    • , Clara Benna
    • , Pio D'Adamo
    • , Daria Diodato
    • , Rodolfo Costa
    • , Caterina Mariotti
    • , Graziella Uziel
    • , Cristina Smiderle
    •  & Massimo Zeviani
  • Letter |

    John Stamatoyannopoulos, Gordon Hager and colleagues report that up to 95% of induced de novo genomic binding by the glucocorticoid receptor is targeted to pre-existing foci of accessible chromatin.

    • Sam John
    • , Peter J Sabo
    • , Robert E Thurman
    • , Myong-Hee Sung
    • , Simon C Biddie
    • , Thomas A Johnson
    • , Gordon L Hager
    •  & John A Stamatoyannopoulos

Technical Report

  • Technical Report |

    Steven McCarroll and colleagues report an analytical framework for characterizing genome deletion polymorphism in populations, applied here to the low coverage genome sequences of 168 individuals from the 1000 Genomes Project. Their population-aware analysis enables structural inference with greater accuracy than previous methods.

    • Robert E Handsaker
    • , Joshua M Korn
    • , James Nemesh
    •  & Steven A McCarroll

Corrigenda

Erratum