Molecular genetics of developmental dyslexia

Chapman, Jade Alice 2011. Molecular genetics of developmental dyslexia. PhD Thesis, Cardiff University.

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Abstract

Developmental Dyslexia (DD) is a complex, cognitive disorder which is characterised by an impairment in reading despite adequate educational, motivational and intellectual opportunities. Family and twin studies have shown that this common neurodevelopmental disorder has a highly heritable component. The aim of this thesis was to identify novel susceptibility variants for DD using several approaches. A candidate gene study was conducted, testing variants within the genes CDC42, PRTG, KIAA0319L, DCDC2b and RIOK3 for association with DD in the Cardiff case-control sample. None of the variants within these genes showed a significant association withDD. A genome-wide association study (GWAS) was conducted in collaboration with other groups as part of the NeuroDys consortium, using DD cases from Europe and population controls. 27 of the most significant SNPs identified were selected and genotyped in a larger replication sample. 8 of these showed a significant association with DD, with the most interesting SNPs within the gene SNX29. An additional GWAS was conducted by the NeuroDys consortium in the form of a pooling study using a larger array. 38 of the most significant SNPs identified were selected for individual genotyping after which 14 remained significant, with the most interesting within the genes TMC1 and WDR78. Another GWAS was conducted in the form of a pooling study using the Cardiff cases and screened controls only. 57 of the most significant SNPs identified were selected for individual genotyping of which 54 remained significant. This study highlighted a number of interesting genes and demonstrated the effect of using a homogeneous case-control sample when conducting pooling studies. Analysis of copy number variants (CNVs) was also conducted using data from the initial NeuroDys GWAS. This study highlighted the technical issues that can affect the outcome of such studies. As such, the CNVs in this study need to be validated before these results can be relied upon. To conclude, some interesting variants have been identified in this thesis but further work is required to confirm these findings.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
ISBN:	9781303222306
Date of First Compliant Deposit:	30 March 2016
Last Modified:	04 Jan 2024 17:05
URI:	https://orca.cardiff.ac.uk/id/eprint/55076

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