Title: The regulatory role of short structural variants and the implication to neurodegenerative diseases in aging
Contact person: Prof. Sivan Korenblit
In the post genome-wide association studies (GWAS) era we are shifting gears toward translation of genetic disease loci to molecular mechanisms of pathogenesis and pinpointing the causal genetic factors and their functional effects. It has been suggested that changes, even subtle, in the expression levels of wild-type genes in the brain can, over years, lead to neurodegenerative diseases. Moreover, differences in gene expression profiles between brain tissues from neurodegenerative disease patients compared to healthy controls have been reported. Short structural variants (SSVs) are short genomic variants (<50 bp) other than SNPs. Recently, there has been increased support for the idea that SSVs, which are largely ignored in large-scale genetic studies, may be involved in many complex diseases, and may also contribute significantly to variation in gene expression in human. We have been studying the expression regulation of key genes implicated in Alzheimer’s (AD) and Parkinson’s (PD) diseases and a wide-spectrum of related disorders. In particular, we focus on noncoding SSVs and their cis-regulatory effects on gene expression using a comprehensive strategy that combines multiple-level approaches.