Grant: Project Grant

Advances in high throughput sequencing technologies have had an immense impact on patients affected by rare genetic conditions by facilitating diagnosis and discovery of novel gene-disease associations. Albeit the vast majority of rare diseases are due to single gene alterations, it is clear that clinical presentation of the disease-causing alteration(s) is dependent on other genetic variants that are present in human genomes. In fact, many of rare diseases display variability in clinical presentations where the patients may not be equally affected despite having the same disease-causing variant(s) (some may be severely affected, and some may not be affected at all). Genetic modifiers are genetic variants in a genome that could either exacerbate (enhance) or alleviate (suppress) the severity of the primary disease-causing variant. Identifying these modifiers in a human genome, despite the unprecedented genomics advances, is extremely difficult. However, by utilizing model organisms, not only can we identify genetic modifiers relevant to different disease conditions, but also, we can learn to develop necessary tools to facilitate modifier identification in human. In this project, we apply high throughput genomics methods, developed in our lab, to search for genetic suppressors relevant to microcephaly using a multicellular model organism Caenorhabditis elegans. Microcephaly, a 'small head syndrome", is a rare disease with variable clinical presentation, where suppressors are likely to play an important role in disease course and may help in facilitating development of much needed treatments.