Volume 43 Issue 6, June 2011

Volume 43 Issue 6

Cover art: "Small Grid Wire Pattern #1" by Willie Little http://www.willielittle.com/

Editorial

  • Editorial |

    Community review of proposed standards is a good strategy to broaden consensus on ways to conduct principled, ethical and efficient research. We are pleased to welcome new partners for our Nature Precedings Data Standards initiative and suggest other standards that could be usefully presented as citable preprints.

Correspondence

News and Views

  • News & Views |

    A new study reveals that the HMG-box transcription factor SOX2 coupled with the chromatin remodeling helicase CHD7 cooperatively regulate target genes that are essential during neural stem cell development. Notably, this complex controls the expression of several disease-associated genes, suggesting a possible mechanistic connection between five seemingly unrelated human genetic disorders.

    • Janusz Puc
    •  & Michael G Rosenfeld
  • News & Views |

    Genetic and gene expression studies have suggested an important role for KLF14 in metabolic disease. A new study now identifies a network of genes whose expression is associated with KLF14 variation in trans, providing a framework for understanding how KLF14 influences disease risk.

    • Mete Civelek
    •  & Aldons J Lusis
  • News & Views |

    A genome-wide association study has identified two new loci modifying pulmonary disease severity in cystic fibrosis. Although this data offers clues to pathways influencing pulmonary function, the underlying genes and mechanisms remain to be elucidated.

    • Heiko Witt

Research Highlights

Perspective

Analysis

  • Analysis |

    Peter Visscher and colleagues report an analysis to partition the genetic variation for several complex traits onto chromosome segments and find that the variation explained is approximately proportional to the total length of genes included within a chromosome segment. They estimate that ~45%, ~17%, ~25% and ~21% of the phenotypic variation, respectively, for height, body mass index, von Willebrand factor and QT interval is tagged by common SNPs, and they partition this variation by chromosome and chromosome segments.

    • Jian Yang
    • , Teri A Manolio
    • , Louis R Pasquale
    • , Eric Boerwinkle
    • , Neil Caporaso
    • , Julie M Cunningham
    • , Mariza de Andrade
    • , Bjarke Feenstra
    • , Eleanor Feingold
    • , M Geoffrey Hayes
    • , William G Hill
    • , Maria Teresa Landi
    • , Alvaro Alonso
    • , Guillaume Lettre
    • , Peng Lin
    • , Hua Ling
    • , William Lowe
    • , Rasika A Mathias
    • , Mads Melbye
    • , Elizabeth Pugh
    • , Marilyn C Cornelis
    • , Bruce S Weir
    • , Michael E Goddard
    •  & Peter M Visscher

Brief Communication

  • Brief Communication |

    Nazneen Rahman and colleagues show that biallelic, loss-of-function mutations in CEP57 cause a constitutional mosaic aneuploidy syndrome. These findings show that CEP57 function is crucial for maintaining correct chromosomal number during cell division.

    • Katie Snape
    • , Sandra Hanks
    • , Elise Ruark
    • , Patricio Barros-Núñez
    • , Anna Elliott
    • , Anne Murray
    • , Andrew H Lane
    • , Nora Shannon
    • , Patrick Callier
    • , David Chitayat
    • , Jill Clayton-Smith
    • , David R FitzPatrick
    • , David Gisselsson
    • , Sebastien Jacquemont
    • , Keiko Asakura-Hay
    • , Mark A Micale
    • , John Tolmie
    • , Peter D Turnpenny
    • , Michael Wright
    • , Jenny Douglas
    •  & Nazneen Rahman

Articles

  • Article |

    Norihiro Kato and colleagues perform a meta-analysis of genome-wide association studies to identify common variants associated with blood pressure variation in east Asians. They identify five new genome-wide significant signals and replicate seven loci previously discovered in populations of European ancestry.

    • Norihiro Kato
    • , Fumihiko Takeuchi
    • , Yasuharu Tabara
    • , Tanika N Kelly
    • , Min Jin Go
    • , Xueling Sim
    • , Wan Ting Tay
    • , Chien-Hsiun Chen
    • , Yi Zhang
    • , Ken Yamamoto
    • , Tomohiro Katsuya
    • , Mitsuhiro Yokota
    • , Young Jin Kim
    • , Rick Twee Hee Ong
    • , Toru Nabika
    • , Dongfeng Gu
    • , Li-ching Chang
    • , Yoshihiro Kokubo
    • , Wei Huang
    • , Keizo Ohnaka
    • , Yukio Yamori
    • , Eitaro Nakashima
    • , Cashell E Jaquish
    • , Jong-Young Lee
    • , Mark Seielstad
    • , Masato Isono
    • , James E Hixson
    • , Yuan-Tsong Chen
    • , Tetsuro Miki
    • , Xueya Zhou
    • , Takao Sugiyama
    • , Jae-Pil Jeon
    • , Jian Jun Liu
    • , Ryoichi Takayanagi
    • , Sung Soo Kim
    • , Tin Aung
    • , Yun Ju Sung
    • , Xuegong Zhang
    • , Tien Yin Wong
    • , Bok-Ghee Han
    • , Shotai Kobayashi
    • , Toshio Ogihara
    • , Dingliang Zhu
    • , Naoharu Iwai
    • , Jer-Yuarn Wu
    • , Yik Ying Teo
    • , E Shyong Tai
    • , Yoon Shin Cho
    •  & Jiang He
  • Article |

    Garry Cutting and colleagues report a genome-wide association and linkage study for loci that affect lung disease severity in cystic fibrosis. They identify two loci that influence lung function in individuals with cystic fibrosis.

    • Fred A Wright
    • , Lisa J Strug
    • , Vishal K Doshi
    • , Clayton W Commander
    • , Scott M Blackman
    • , Lei Sun
    • , Yves Berthiaume
    • , David Cutler
    • , Andreea Cojocaru
    • , J Michael Collaco
    • , Mary Corey
    • , Ruslan Dorfman
    • , Katrina Goddard
    • , Deanna Green
    • , Jack W Kent Jr
    • , Ethan M Lange
    • , Seunggeun Lee
    • , Weili Li
    • , Jingchun Luo
    • , Gregory M Mayhew
    • , Kathleen M Naughton
    • , Rhonda G Pace
    • , Peter Paré
    • , Johanna M Rommens
    • , Andrew Sandford
    • , Jaclyn R Stonebraker
    • , Wei Sun
    • , Chelsea Taylor
    • , Lori L Vanscoy
    • , Fei Zou
    • , John Blangero
    • , Julian Zielenski
    • , Wanda K O'Neal
    • , Mitchell L Drumm
    • , Peter R Durie
    • , Michael R Knowles
    •  & Garry R Cutting
  • Article |

    Kathryn Anderson and colleagues use mouse genetics to define unexpected relationships between the retrograde ciliary motor gene Dync2h1 and other genes required for trafficking in primary cilia. Their findings argue that the mutant phenotypes in these models result from defects in cilia architecture rather than direct roles in signaling.

    • Polloneal Jymmiel R Ocbina
    • , Jonathan T Eggenschwiler
    • , Ivan Moskowitz
    •  & Kathryn V Anderson
  • Article |

    Ido Golding and colleagues examine transcriptional time series in Escherichia coli, characterizing mRNA copy number statistics for 20 promoters at single transcript resolution. They find that the degree of burstiness depends primarily on the level of gene expression.

    • Lok-hang So
    • , Anandamohan Ghosh
    • , Chenghang Zong
    • , Leonardo A Sepúlveda
    • , Ronen Segev
    •  & Ido Golding

Letters

  • Letter |

    Tim Spector, Mark McCarthy and colleagues show that an imprinted cis-acting regulatory variant of KLF14 previously associated with type 2 diabetes and HDL-cholesterol levels acts as a master trans regulator of adipose gene expression. The study provides a framework for understanding the effects of KLF14 on disease risk.

    • the MuTHER Consortium
    • , Kerrin S Small
    • , Åsa K Hedman
    • , Elin Grundberg
    • , Alexandra C Nica
    • , Gudmar Thorleifsson
    • , Augustine Kong
    • , Unnur Thorsteindottir
    • , So-Youn Shin
    • , Hannah B Richards
    • , Nicole Soranzo
    • , Kourosh R Ahmadi
    • , Cecilia M Lindgren
    • , Kari Stefansson
    • , Emmanouil T Dermitzakis
    • , Panos Deloukas
    • , Timothy D Spector
    •  & Mark I McCarthy
  • Letter |

    Karsten Suhre and colleagues report a genome-wide association study of metabolic traits in human urine, using NMR spectrometry to measure 59 metabolites in urine from participants. They identify five loci influencing urine metabolite levels and point to a missense variant in AGXT2 as the likely cause of hyper-β-aminoisobutyric aciduria, a common inborn error of metabolism.

    • Karsten Suhre
    • , Henri Wallaschofski
    • , Johannes Raffler
    • , Nele Friedrich
    • , Robin Haring
    • , Kathrin Michael
    • , Christina Wasner
    • , Alexander Krebs
    • , Florian Kronenberg
    • , David Chang
    • , Christa Meisinger
    • , H-Erich Wichmann
    • , Wolfgang Hoffmann
    • , Henry Völzke
    • , Uwe Völker
    • , Alexander Teumer
    • , Reiner Biffar
    • , Thomas Kocher
    • , Stephan B Felix
    • , Thomas Illig
    • , Heyo K Kroemer
    • , Christian Gieger
    • , Werner Römisch-Margl
    •  & Matthias Nauck
  • Letter |

    Christopher Haiman and colleagues report a genome-wide association study for prostate cancer in African-American males drawn from 11 epidemiological studies of prostate cancer, with replication including individuals of African ancestry from 10 additional studies worldwide. They identify a new susceptibility locus on chromosome 17q21, for which the risk allele shows a higher frequency in men of African ancestry than in other populations. This may explain some of the increased incidence of prostate cancer in men of African ancestry.

    • Christopher A Haiman
    • , Gary K Chen
    • , William J Blot
    • , Sara S Strom
    • , Sonja I Berndt
    • , Rick A Kittles
    • , Benjamin A Rybicki
    • , William B Isaacs
    • , Sue A Ingles
    • , Janet L Stanford
    • , W Ryan Diver
    • , John S Witte
    • , Ann W Hsing
    • , Barbara Nemesure
    • , Timothy R Rebbeck
    • , Kathleen A Cooney
    • , Jianfeng Xu
    • , Adam S Kibel
    • , Jennifer J Hu
    • , Esther M John
    • , Serigne M Gueye
    • , Stephen Watya
    • , Lisa B Signorello
    • , Richard B Hayes
    • , Zhaoming Wang
    • , Edward Yeboah
    • , Yao Tettey
    • , Qiuyin Cai
    • , Suzanne Kolb
    • , Elaine A Ostrander
    • , Charnita Zeigler-Johnson
    • , Yuko Yamamura
    • , Christine Neslund-Dudas
    • , Jennifer Haslag-Minoff
    • , William Wu
    • , Venetta Thomas
    • , Glenn O Allen
    • , Adam Murphy
    • , Bao-Li Chang
    • , S Lilly Zheng
    • , M Cristina Leske
    • , Suh-Yuh Wu
    • , Anna M Ray
    • , Anselm J M Hennis
    • , Michael J Thun
    • , John Carpten
    • , Graham Casey
    • , Erin N Carter
    • , Edder R Duarte
    • , Lucy Y Xia
    • , Xin Sheng
    • , Peggy Wan
    • , Loreall C Pooler
    • , Iona Cheng
    • , Kristine R Monroe
    • , Fredrick Schumacher
    • , Loic Le Marchand
    • , Laurence N Kolonel
    • , Stephen J Chanock
    • , David Van Den Berg
    • , Daniel O Stram
    •  & Brian E Henderson
  • Letter |

    Jamie Craig and colleagues report a genome-wide association study for advanced open angle glaucoma (OAG). They identify variants near TMCO1 and in CDKN2B-AS1 associated with OAG and show retinal expression of genes at both loci.

    • Kathryn P Burdon
    • , Stuart Macgregor
    • , Alex W Hewitt
    • , Shiwani Sharma
    • , Glyn Chidlow
    • , Richard A Mills
    • , Patrick Danoy
    • , Robert Casson
    • , Ananth C Viswanathan
    • , Jimmy Z Liu
    • , John Landers
    • , Anjali K Henders
    • , John Wood
    • , Emmanuelle Souzeau
    • , April Crawford
    • , Paul Leo
    • , Jie Jin Wang
    • , Elena Rochtchina
    • , Dale R Nyholt
    • , Nicholas G Martin
    • , Grant W Montgomery
    • , Paul Mitchell
    • , Matthew A Brown
    • , David A Mackey
    •  & Jamie E Craig
  • Letter |

    Simon John and Mounira Hmani-Aifa and colleagues show that mutation of the serine protease gene Prss56 causes elevated intraocular pressure and angle closure glaucoma in mice. They also identified PRSS56 mutations that cause posterior microphthalmia in humans.

    • K Saidas Nair
    • , Mounira Hmani-Aifa
    • , Zain Ali
    • , Alison L Kearney
    • , Salma Ben Salem
    • , Danilo G Macalinao
    • , Ioan M Cosma
    • , Walid Bouassida
    • , Bochra Hakim
    • , Zeineb Benzina
    • , Ileana Soto
    • , Peter Söderkvist
    • , Gareth R Howell
    • , Richard S Smith
    • , Hammadi Ayadi
    •  & Simon W M John
  • Letter |

    Evan Eichler, Jay Shendure and colleagues sequenced the exomes of 20 sporadic cases of autism spectrum disorder and their unaffected parents. They identified potentially causative de novo mutations in four cases, including a frameshift in FOXP1, a splice-site mutation in GRIN2B and missense variants in SCN1A and LAMC3.

    • Brian J O'Roak
    • , Pelagia Deriziotis
    • , Choli Lee
    • , Laura Vives
    • , Jerrod J Schwartz
    • , Santhosh Girirajan
    • , Emre Karakoc
    • , Alexandra P MacKenzie
    • , Sarah B Ng
    • , Carl Baker
    • , Mark J Rieder
    • , Deborah A Nickerson
    • , Raphael Bernier
    • , Simon E Fisher
    • , Jay Shendure
    •  & Evan E Eichler
  • Letter |

    Murat Gunel and colleagues report the identification of mutations in the laminin γ3 gene that cause complex bilateral occipital cortical gyration abnormalities in humans.

    • Tanyeri Barak
    • , Kenneth Y Kwan
    • , Angeliki Louvi
    • , Veysi Demirbilek
    • , Serap Saygı
    • , Beyhan Tüysüz
    • , Murim Choi
    • , Hüseyin Boyacı
    • , Katja Doerschner
    • , Ying Zhu
    • , Hande Kaymakçalan
    • , Saliha Yılmaz
    • , Mehmet Bakırcıoğlu
    • , Ahmet Okay Çağlayan
    • , Ali Kemal Öztürk
    • , Katsuhito Yasuno
    • , William J Brunken
    • , Ergin Atalar
    • , Cengiz Yalçınkaya
    • , Alp Dinçer
    • , Richard A Bronen
    • , Shrikant Mane
    • , Tayfun Özçelik
    • , Richard P Lifton
    • , Nenad Šestan
    • , Kaya Bilgüvar
    •  & Murat Günel
  • Letter |

    Christopher Klein and colleagues report that DNMT1 is disrupted in hereditary sensory neuropathy with dementia and hearing loss. The mutations lead to reduced methyltransferase activity, leading to global hypomethylation and site-specific hypermethylation.

    • Christopher J Klein
    • , Maria-Victoria Botuyan
    • , Yanhong Wu
    • , Christopher J Ward
    • , Garth A Nicholson
    • , Simon Hammans
    • , Kaori Hojo
    • , Hiromitch Yamanishi
    • , Adam R Karpf
    • , Douglas C Wallace
    • , Mariella Simon
    • , Cecilie Lander
    • , Lisa A Boardman
    • , Julie M Cunningham
    • , Glenn E Smith
    • , William J Litchy
    • , Benjamin Boes
    • , Elizabeth J Atkinson
    • , Sumit Middha
    • , P James B Dyck
    • , Joseph E Parisi
    • , Georges Mer
    • , David I Smith
    •  & Peter J Dyck
  • Letter |

    Tania Attié-Bitach and colleagues report that biallelic mutations in KIF7, a component of the Hedgehog signaling pathway, cause hydrolethalus and acrocallosal syndromes. They also present evidence that heterozygous KIF7 mutations contribute to the allelic load and phenotypic spectrum of other cilia disorders.

    • Audrey Putoux
    • , Sophie Thomas
    • , Karlien L M Coene
    • , Erica E Davis
    • , Yasemin Alanay
    • , Gönül Ogur
    • , Elif Uz
    • , Daniela Buzas
    • , Céline Gomes
    • , Sophie Patrier
    • , Christopher L Bennett
    • , Nadia Elkhartoufi
    • , Marie-Hélène Saint Frison
    • , Luc Rigonnot
    • , Nicole Joyé
    • , Solenn Pruvost
    • , Gulen Eda Utine
    • , Koray Boduroglu
    • , Patrick Nitschke
    • , Laura Fertitta
    • , Christel Thauvin-Robinet
    • , Arnold Munnich
    • , Valérie Cormier-Daire
    • , Raoul Hennekam
    • , Estelle Colin
    • , Nurten Ayse Akarsu
    • , Christine Bole-Feysot
    • , Nicolas Cagnard
    • , Alain Schmitt
    • , Nicolas Goudin
    • , Stanislas Lyonnet
    • , Férechté Encha-Razavi
    • , Jean-Pierre Siffroi
    • , Mark Winey
    • , Nicholas Katsanis
    • , Marie Gonzales
    • , Michel Vekemans
    • , Philip L Beales
    •  & Tania Attié-Bitach
  • Letter |

    Raymond Poot and colleagues report that Chd7, a chromatin remodeler associated with CHARGE syndrome, and Sox2, a transcription factor associated with an anopthalmia syndrome, physically interact, have overlapping binding sites and regulate a set of common target genes.

    • Erik Engelen
    • , Umut Akinci
    • , Jan Christian Bryne
    • , Jun Hou
    • , Cristina Gontan
    • , Maaike Moen
    • , Dorota Szumska
    • , Christel Kockx
    • , Wilfred van IJcken
    • , Dick H W Dekkers
    • , Jeroen Demmers
    • , Erik-Jan Rijkers
    • , Shoumo Bhattacharya
    • , Sjaak Philipsen
    • , Larysa H Pevny
    • , Frank G Grosveld
    • , Robbert J Rottier
    • , Boris Lenhard
    •  & Raymond A Poot