The University of Southampton
University of Southampton Institutional Repository

Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia

Record type: Article

Linkage between developmental dyslexia (DD) and chromosome 6p has been replicated in a number of independent samples. Recent attempts to identify the gene responsible for the linkage have produced inconsistent evidence for association of DD with a number of genes in a 575-kb region of chromosome 6p22.2, including VMP, DCDC2, KIAA0319, TTRAP, and THEM2. We aimed to identify the specific gene or genes involved by performing a systematic, high-density (~2-3-kb intervals) linkage disequilibrium screen of these genes in an independent sample, incorporating family-based and case-control designs in which dyslexia was defined as an extreme representation of reading disability. Using DNA pooling, we first observed evidence for association with 17 single-nucleotide polymorphisms (SNPs), 13 of which were located in the KIAA0319 gene (P < .01.003). After redundant SNPs were excluded, 10 SNPs were individually genotyped in 223 subjects with DD and 273 controls. Those SNPs that were significant at P <_ .05 were next genotyped in a semi-independent sample of 143 trios of probands with DD and their parents, to control for possible population stratification. Six SNPs showed significant evidence of association in both samples (P <_ .04-.002), including a SNP (rs4504469) in exon 4 of the KIAA0319 gene that changes an amino acid (P = .002; odds ratio 1.5). Logistic regression analysis showed that two SNPs (rs4504469 and rs6935076) in the KIAA0319 gene best explained DD status. The haplotype composed of these two markers was significantly associated with DD (global P = .00001 in the case-control sample; P = .02 in trios). This finding was largely driven by underrepresentation of the most common haplotype in cases (P = .00003 in the case-control sample; P = .006 in trios; 1-degree-of-freedom tests). Our data strongly implicate KIAA0319 as a susceptibility gene for dyslexia. The gene product is expressed in brain, but its specific function is currently unknown.

PDF 42045.web.pdf - Version of Record
Restricted to Repository staff only
Download (231kB)

Citation

Cope, Natalie, Harold, Denise, Hill, Gary, Moskvina, Valentina, Stevenson, Jim, Holmans, Peter, Owen, Michael J., O'Donovan,, Michael C. and Julie, Williams (2005) Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia The American Journal of Human Genetics, 76, (4), pp. 581-591. (doi:10.1086/429131).

More information

Published date: 2005

Identifiers

Local EPrints ID: 18398
URI: http://eprints.soton.ac.uk/id/eprint/18398
ISSN: 0002-9297
PURE UUID: 84ad264e-3771-43f7-8e95-1be7e801c258

Catalogue record

Date deposited: 05 Jan 2006
Last modified: 17 Jul 2017 16:36

Export record

Altmetrics

Contributors

Author: Natalie Cope
Author: Denise Harold
Author: Gary Hill
Author: Valentina Moskvina
Author: Jim Stevenson
Author: Peter Holmans
Author: Michael J. Owen
Author: Michael C. O'Donovan,
Author: Williams Julie

University divisions


Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×