UBC Theses and Dissertations
A genome-wide linkage scan and targeted family-based association analysis of dyslexia Ryan, Jane
As a specific reading disability with a neurobiological origin, developmental dyslexia is distinct from reading difficulties due to sensory impairments in vision or hearing. The disability is commonly attributed to a core deficit in phonological processing, the understanding of how phonemes, syllables and words are used in a language. Dyslexia is a complex genetic disorder with a strong genetic component; nine susceptibility loci (DYX1-9) have been identified with eight other dyslexia linkages lacking gene symbols also reported. The statistical methods of linkage and association were employed to investigate the genetic susceptibility for phonological coding dyslexia (PCD), a common form of dyslexia characterized by difficulties in single word decoding and resulting from deficits in phonological processing. A genome-wide non-parametric linkage (NPL) study and four targeted fine-mapping family-based association studies were performed to locate the genes predisposing to PCD in 101 Canadian families with multiple affected members. The NPL scan identified suggestive evidence for linkage with PCD at the two novel regions 16p12 and 4q12-q13, and provided independent confirmation of linkage to the well-replicated DYX3 locus (at 2p21). Some support for linkage was noted at a further five regions previously linked to dyslexia, while no linkage was detected at five other reportedly-linked regions, in particular, no linkage to DYX2 (6p22.2). Four regions (16p12, 2p21, 4q12-q13 and 6p22.2) were tested for association with PCD in 83 trios, a subset of the 101 families, using the transmission disequilibrium test (TDT) and the affected family-based controls (AFBAC) test. Association was detected in each of the three PCD-linked regions in the NPL scan; none of the tested marker alleles was associated with PCD in the 6p22.2 region. Four candidate genes were identified, two of which belong to the same gene family, with a possible role in the neurodevelopmental mechanisms underlying reading.
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