A sibling-pair based approach for mapping genetic loci that influence quantitative measures of reading disability

Family and twin studies consistently demonstrate a significant role for gen etic factors in the aetiology of the reading disorder dyslexia. However, dy slexia is complex at both the genetic and phenotypic levels, and currently the nature of the core deficit or deficits remains uncertain. Traditional a pproaches for mapping disease genes, originally developed for single-gene d isorders, have limited success when there is not a simple relationship betw een genotype and phenotype. Recent advances in high-throughput genotyping t echnology and quantitative statistical methods have made a new approach to identifying genes involved in complex disorders possible. The method involv es assessing the genetic similarity of many sibling pairs along the lengths of all their chromosomes and attempting to correlate this similarity with that of their phenotypic scores. We are adopting this approach in an ongoin g genome-wide search for genes involved in dyslexia susceptibility, and hav e already successfully applied the method by replicating results from previ ous studies suggesting that a quantitative trait locus at 6p21.3 influences reading disability. (C) 2000 Harcourt Publishers Ltd.