Analysis of dyslexia candidate genes in the Raine cohort representing the general Australian population

Abstract

Several genes have been suggested as dyslexia candidates. Some of these candidate genes have been recently shown to be associated with literacy measures in sample cohorts derived from the general population. Here, we have conducted an association study in a novel sample derived from the Australian population (the Raine cohort) to further investigate the role of dyslexia candidate genes. We analysed markers, previously reported to be associated with dyslexia, located within the MRPL19/C2ORF3, KIAA0319, DCDC2 and DYX1C1 genes in a sample of 520 individuals and tested them for association with reading and spelling measures. Association signals were detected for several single nucleotide polymorphisms (SNPs) within DYX1C1 with both the reading and spelling tests. The high linkage disequilibrium (LD) we observed across the DYX1C1 gene suggests that the association signal might not be refined by further genetic mapping.

Figure 1. SNPs location and LD across DYX1C1

The top of the figure shows the structure of the DYX1C1 gene (blue arrow) indicating the position of exons (blue vertical lines), with an indication of their genomic location on chromosome 15. In total, 29 SNPs were analysed across an 86-kb interval. Black lines indicate the position of each SNP within DYX1C1. Inter-SNP LD was generated with Haploview. (a) D′ values are reported within cells while empty red cells represent full LD and empty blue cells represent lack of LD. (b) r² values are reported within cells where empty white cells represent lack of LD and darker shadings represent increasingly stronger LD. Haploview identified six LD blocks (black solid lines) using the confidence interval method (Gabriel et al. 2002), but LD is strong all across the examined region.