5th meeting of the Free&Open Bioinformatics Association (FOBIA)
Sprache des Tagungstitel:
Autism Spectrum Disorders (ASD) is a well-studied neurodevelopmental disorder with a prevalence of 0.3-0.6%, and is characterized by an impairment of social skills and communication, repetitive patterns of behaviors, and restricted interests. Beside these phenotypes, 30-40% individuals with ASD are diagnosed with epilepsy, 60-80% show motoric abnormalities, and 70-80% are male. Genetic factors are one of major causes for ASD as has been shown by family and twin studies, however they are poorly understood.
We investigated neurodevelopmental dysfunctions in autism spectrum disorders (ASD) by a integrative analysis including the two largest genome-wide studies on associations between copy number aberrations (CNA) and ASD, the "BioGPS" tissue atlas, the "Allen Brain Atlas", and in situ hybridization histochemistry data from the developing mouse brain. In contrast to the original association studies, we considered "ASD candidate genes" each of which is the only CNA-impaired gene in an ASD case, therefore, presumably causing ASD. We found that many ASD candidate genes are related to synaptic adhesion which hints at impairments of synaptic connections. ASD candidate genes that are indentified independently in both CNA studies are the neurexins CNTNAP2 and NRXN1, the catenin CTNNA3, the cadherin CDH13, and the contactins CNTN5 and CNTN6. Gene expression data indicate that the ASD candidate genes are primarily expressed in the cerebellum, especially in the vermis, where we suspect ASD's neurodevelopmental pathogenesis. The cerebellum as the location of ASD's pathogenesis can explain the high male to female ratio in ASD and secondary ASD phenotypes like motoric impairments.