A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation
Date
2009
Authors
Tarpey, P.
Smith, R.
Pleasance, E.
Whibley, A.
Edkins, S.
Hardy, C.
O'Meara, S.
Latimer, C.
Dicks, E.
Menzies, A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Nature Genetics, 2009; 41(5):535-543
Statement of Responsibility
Patrick S Tarpey...Cheryl Shoubridge, Mark Corbett, Eric Haan...Tod Fullston...Jozef Gecz... et al.
Conference Name
DOI
Abstract
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.