January 10th, 2018
Association of Dyslexia with Genes
Attempts to identify the association of dyslexia with genes reinforce how complex such association is. For instance, though there exist strong evidence of genes involvement in the development of dyslexia, even the most implicated genes and genetic loci have not replicated such associations in all sample populations (Gabel et al. 174). Such is exemplified by DYX1C1, the gene that was first suggested to exhibit dyslexia vulnerability, whose functional alleles that were implicated for dyslexia susceptibility in Finnish population, have, in subsequent independent studies, lacked a significant association to the disorder (Wang et al. 515). Additionally, gene variants identified to be susceptible to dyslexia continue to exist in individuals who do not have RD (Gabel et al. 174). Further, despite the heritability of RD being acknowledged, the heritability rates suggested in various studies depict a rather wide range – 29% to 82% (Gabel et al. 175). Although such challenges to identifying pathways that link genes or specific genetic loci to dyslexia exist, the identification of candidate genes, especially KIAA0319, DYX1C1 and DCDC2, has enabled research to progress towards establishing the molecular and cellular mechanisms of the disorder (Gabel et al. 174).
RD risk is associated with “nine chromosomal loci [DYX1-DYX9] across the genome (Gabel et al. 175) in varying replications. The most replicated among the nine loci, have been those found on “chromosome 1p34-p36 (DYX8), 2p (DYX3), 6p21.3 (DYX2), and 15q21 (DYX1), [while those at locations] 3p12-q12 (DYX5), 6q13-q16 (DYX4), 11p15 (DYX7), 18p11 (DYX6), and Xq27 (DYX9)” have been replicated either once or have never been replicated (Gabel et al. 175). In the section below the most replicated genes DYXIC1, found at the chromosomal locus DYX1, and KIAA0319 and DCDC2, found at the chromosomal locus DYX2, are discussed, with a brief mention of other candidate genes provided thereafter.
DYX1C1: Implicated Gene at Locus DYX1
The link between genes and dyslexia was first identified with DYX1CI, when in the year 2000, observations of chromosomal translocation in two Finnish families that had a history of dyslexia, revealed a breakpoint within the DYX1 locus (Gabel et al. 175). Following subsequent assays, the breakpoint was noted to affect “the exons [the non-coding sequences] of the gene EKN1, which was subsequently renamed Dyslexia Susceptibility 1 Candidate 1 (DYX1C1)” (Gabel et al. 175). Despite such early implication and significant association in the Finnish samples (the two families), subsequent research using samples from Italy, US and UK have not found such significant correlation, indicating that the gene’s putative alleles described in the Finnish study, may not be predominant risk alleles for RD (Wang et al. 515; Gabel et al. 175). However, other studies in Germany and US have indicated associations between RD and a “RD-related single nucleotide polymorphism (SNP) in DYX1C1” (Brkanac et al. and Dahdouh et al. qtd. in Gabel et al. 175). Similarly, a study in Italy using the same sample as that which did not reveal significant association between RD and DYX1C1, found associations to exist with verbal and short-term memory impairments (Marino et al. qtd. in Gabel et al. 175). Such recent observations suggest the existence of some association between DYX1C1 variants with RD or its component features. Go to part 3 here