ORIGINAL ARTICLE

Genomewide scan identifies susceptibility locus for dyslexia on Xq27 in an extended Dutch family

C G F de Kovel¹, F A Hol², J G A M Heister², J J H T Willemen², L A Sandkuijl³, B Franke², G W Padberg⁴

¹ Department of Theoretical Biology, University of Leiden, NL-2311 GP Leiden, The Netherlands
² Department of Human Genetics, University Medical Centre Nijmegen, NL-6500 HB Nijmegen, The Netherlands
³ Department Medical Statistics and Bio Informatics, Leiden University Medical Centre, NL-2300 RC Leiden, The Netherlands
⁴ Department of Neurology, University Medical Centre Nijmegen, NL-6500 HB Nijmegen, The Netherlands

Correspondence to:
Correspondence to:
Dr C G F de Kovel
University Leiden, Theoretical Biology, Kaiserstraat 63, 2311 GP Leiden, The Netherlands; dekovel{at}rulsfb.leidenuniv.ne

Context: Dyslexia is a common disorder with a strong genetic component, but despite significant research effort, the aetiology is still largely unknown.

Objective: To identify loci contributing to dyslexia risk.

Methods: This was a genomewide linkage analysis in a single large family. Dutch families with at least two first degree relatives suffering from dyslexia participated in the study. Participants were recruited through an advertisement campaign in papers and magazines. The main outcome measure was linkage between genetic markers and dyslexia phenotype.

Results: Using parametric linkage analysis, we found strong evidence for a locus influencing dyslexia on Xq27.3 (multipoint lod = 3.68). Recombinations in two family members flanked an 8 cM region, comprising 11 currently confirmed genes. All four males carrying the risk haplotype had very low scores on the reading tests. The presentation in females was more variable, but 8/9 females carrying the risk haplotype were diagnosed dyslexic by our composite score, so we considered the putative risk allele to be dominant with reduced penetrance. Linkage was not found in an additional collection of affected sibling pairs.

Conclusions: A locus influencing dyslexia risk is probably located between markers DXS1227 and DXS8091 on the X chromosome, closely situated to a locus indicated by a published genome scan of English sibling pairs. Although the locus may not be a common cause for dyslexia, the relatively small and gene poor region offers hope to identify the responsible gene.

Abbreviations: QTL, quantitative trait locus

Keywords: dyslexia; reading disability; genome scan; linkage; X chromosome

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