Single nucleotide polymorphism association studies of ABCA13 and ABHD11 genes and the bioinformatics analysis of the autism candidate genes localized on chromosome 7
Autism, Aspergers Syndrome and Pervasive Developmental Delay-Not Otherwise Specified (PDD-NOS), among others, fall under an umbrella of disorders known as Autism Spectrum Disorder. Twin studies show that autism is a highly heritable disorder. More than 100 genes have been implicated in the aetiology of autism, each of which is involved in numerous biological processes and a variety of molecular interactions. William-Beuren syndrome is a multisystem developmental disorder caused by the deletion of contiguous genes at the 7q11.23 position. The aims of this study were (i) to genotype three SNPs (rs10279013, rs2293484 and rs17060) in the ABHD11 and ABCA13 genes, respectively, using Taqman® SNP Genotyping assays to detect association with autism in three distinct South African (SA) ethnic groups (Black, Caucasian and Mixed), and (ii) to ascertain common pathways or regulating transcription factors for genes on chromosome 7 that may attribute to it being an “autism hotspot”. Chapter 3 objectives were to identify potential candidate genes using STRING analysis and the Gene Cards database. The Taqman® study indicated significant association for SNP rs2293484 in the South African Caucasian group, as well as for the G allele in the South African Mixed group, where p<0.001. STRING analysis yielded 2 new candidate genes, FZD1 and FZD9. It was also found that the Wnt pathway in mammals plays a significant role in both ASDs and cancer, and there is a definite link between genes regulating cancer, and genes implicated in autism. The study provides evidence for not only the association of the investigated SNP in a South African population, but also provides evidence for the co-morbidity of several neurological and psychological disorders such as depression and bipolar disorder with autism.