Article

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

Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
Nature Genetics (impact factor: 35.53). 05/2009; 41(5):535-43. DOI:10.1038/ng.367 pp.535-43
Source: PubMed

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.

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Keywords

coding exons
 
constitutional disease-causing mutations
 
disease-causing sequence variants
 
genes
 
human complex disease
 
key future strategy
 
largest direct screen
 
normal existence
 
SYP
 
whole-genome sequencing screens
 
X chromosome
 
X-chromosome genes
 
X-linked mental retardation
 
XLMR
 

Patrick S Tarpey