A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation
By P. Tarpey, Raffaella Smith, E. Pleasance, Annabel Whibley, S. Edkins, Claire W. Hardy, S. O’Meara, Calli Latimer, E. Dicks, A. Menzies and 70 more. Nature Genetics, 2009
635 citations recorded by the source corpus.
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.
Subfields: Genetics, Plant Science
View Paper: https://www.semanticscholar.org/paper/5f261711a5d50208a4f6e886536b45b86d79f071
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Citations in the corpus
- Rare and Common Variants: Twenty arguments (2011, background): “Probably the most comprehensive survey of this model is the demonstration that one-quarter of the cases of X-chromosome-linked intellectual disability can be ascribed to rare protein-coding mutations, which were discovered by comprehensive sequencing of X-chromosomal exon”
- A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation (2010, positive): “The transcriptional regulatory factors consist of both putative DNA sequence-specific binding factors—among these, a number of zinc finger proteins, including ZNF41, ZNF81, ZNF674, and ZNF711 (Chiurazzi et al., 2008; Kleefstra et al., 2004; Lugtenberg et al., 2006; Shoichet et al., 2003; Tarpey et a”
- A de novo paradigm for mental retardation (2010, background): “In addition, targeted resequencing of the coding exons of the X chromosome revealed nine genes associated with X-linked forms of mental retardatio”
- Deep sequencing reveals 50 novel genes for recessive cognitive disorders (2011, background): “In a previous study, 1% of the protein-truncating mutations on the X chromosome were found to be unrelated to disease 31 , and in our study, 12 observed inactivating mutations did not co-segregate with intellectual disability (see Supplementary Table 4).”