Linkage and next generation sequencing (NGS) data in six large Danish families with dyslexia

Abstract Dyslexia is a common learning disability exhibited as a delay in acquiring reading skills despite adequate intelligence, and reading single real words are impaired in many dyslexics. Reading disability or developmental dyslexia (DD) is a neurodevelopmental disorder affecting children globally, and the molecular mechanisms underlying it are largely underdetermined, while loci and susceptibility genes are suggested by genetic mapping in families or cohorts and by genome wide association studies (GWAS). To identify a possible genetic cause, we genotyped and performed genome wide linkage analysis employing the programs LIPED and SNP6-LINK of six multigenerational families with autosomal dominant inherited dyslexia. The linkage analyses resulted in informative haplotypes segregating with the dyslectic trait in all families and a LOD score of Z>4 at 13q12.3 and 19p13.3, and a LOD score of Z>3 at 15q23-q24.1, 18q11.21, and 21q22.3. The five mapped regions are supported by previous linkage or associations studies of dyslexia. Whole genome sequencing (WGS) of affected individuals in the six family’s revealed rare regulatory variants in the mapped regions.