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A dyslexia susceptibility locus ( DYX7 ) linked to dopamine D4 receptor (DRD4) region on chromosome 11p15.5
Author(s) -
Hsiung GingYuek R.,
Kaplan Bonnie J.,
Petryshen Tracey L.,
Lu Shao,
Field L. Leigh
Publication year - 2003
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.20082
Subject(s) - dyslexia , hras , genetics , linkage disequilibrium , locus (genetics) , allele , biology , psychology , exon , genetic linkage , haplotype , gene , reading (process) , kras , mutation , political science , law
Dyslexia is a disability in acquiring reading and spelling skills that is independent of general intelligence and educational opportunity, and is highly heritable. It is known that dyslexia often co‐occurs with attention deficit hyperactivity disorder (ADHD), and the 7‐repeat allele of the 48‐bp tandem repeat in exon 3 of the dopamine D4 receptor (DRD4) has been implicated in ADHD. We, therefore, investigated DRD4 as a candidate gene for dyslexia by testing for linkage and association with 14 markers at and around the DRD4 locus on chromosome 11p15.5. Using 100 families having at least two siblings affected with dyslexia, model‐free linkage analysis revealed evidence for linkage to the DRD4‐exon 3 repeat (two‐point MFLOD = 2.27, P = 0.001) and to HRAS located just proximal to DRD4 (two‐point MFLOD = 2.68, P = 0.0004). Evidence for linkage was maximal between DRD4 and HRAS (three‐point MFLOD = 3.57, P = 0.00005). However, linkage disequilibrium analysis showed no significant evidence for association between dyslexia and DRD4 or HRAS. In particular, dyslexic subjects showed no significant increase of the DRD4 7‐repeat allele associated with ADHD. It is possible that other DRD4 variants, not in strong linkage disequilibrium with the exon 3 repeat polymorphism, or alternatively, another gene very closely linked to DRD4, may influence susceptibility to dyslexia. © 2003 Wiley‐Liss, Inc.