A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation

Patrick S. Tarpey, Raffaella Smith, Erin Pleasance, Annabel Whibley, Sarah Edkins, Claire Hardy, Sarah O'Meara, Calli Latimer, Ed Dicks, Andrew Menzies, Phil Stephens, Matt Blow, Chris Greenman, Yali Xue, Chris Tyler-Smith, Deborah Thompson, Kristian Gray, Jenny Andrews, Syd Barthorpe, Gemma BuckJennifer Cole, Rebecca Dunmore, David Jones, Mark Maddison, Tatiana Mironenko, Rachel Turner, Kelly Turrell, Jennifer Varian, Sofie West, Sara Widaa, Paul Wray, Jon Teague, Adam Butler, Andrew Jenkinson, Mingming Jia, David Richardson, Rebecca Shepherd, Richard Wooster, M. Isabel Tejada, Francisco Martinez, Gemma Carvill, Rene Goliath, Arjan P M De Brouwer, Hans Van Bokhoven, Hilde Van Esch, Jamel Chelly, Martine Raynaud, Hans Hilger Ropers, Fatima E. Abidi, Anand K. Srivastava, James Cox, Ying Luo, Uma Mallya, Jenny Moon, Josef Parnau, Shehla Mohammed, John L. Tolmie, Cheryl Shoubridge, Mark Corbett, Alison Gardner, Eric Haan, Sinitdhorn Rujirabanjerd, Marie Shaw, Lucianne Vandeleur, Tod Fullston, Douglas F. Easton, Jackie Boyle, Michael Partington, Anna Hackett, Michael Field, Cindy Skinner, Roger E. Stevenson, Martin Bobrow, Gillian Turner, Charles E. Schwartz, Jozef Gecz, F. Lucy Raymond, P. Andrew Futreal, Michael R. Stratton

Research output: Contribution to journalArticlepeer-review

486 Scopus citations


Large-scale systematic resequencing has been proposed as the key future strategy for the discovery of rare, disease-causing sequence variants across the spectrum of human complex disease. We have sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation (XLMR), the largest direct screen for constitutional disease-causing mutations thus far reported. The screen has discovered nine genes implicated in XLMR, including SYP, ZNF711 and CASK reported here, confirming the power of this strategy. The study has, however, also highlighted issues confronting whole-genome sequencing screens, including the observation that loss of function of 1% or more of X-chromosome genes is compatible with apparently normal existence.

Original languageEnglish (US)
Pages (from-to)535-543
Number of pages9
JournalNature Genetics
Issue number5
StatePublished - May 2009

ASJC Scopus subject areas

  • Genetics


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