Co-expression study among Y chromosome genes and autosomal genes and its relation to Autism Spectrum Disorders (ASD)

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disease with high incidence in population, and which presents an ample spectrum of severity and impairments. Interesting, there is a distortion in male to female ratio being 4:1. Many assumptions were created focusing in sexual dimorphism to explain this ratio, however male predisposition to autistic disorder remains unexplained. Recently, studies with Drosophila melanogaster showed that there is a class of autosomal/X genes that vary in expression consistently across multiple Y introgression experiments. In human, this kind of variation is practically unexplored. Thus, in this proposal we aim to study whether changes in expression of Y chromosome genes are accompanied by other autosomal/X genes using co-expression matrix (WGCNA, implemented in R) in male samples from published microarray studies. Still, we intend to investigate whether this co-expression is different when we compare normal and autistic individuals. Together with this proposal, we want to identify human orthologs genes using the genes that showed changes in the expression due differences in Y chromosome found in D. Melanogaster, and verify if this set of human genes are associated to autism. This approach could suggest a Y chromosome effect in autism, leading to new perspectives of the roles of Y chromosome genes, and better comprehension of molecular mechanisms involved in ASD.