Title: Role of NR2E1 RNA Structure in Human Health and Disease
Presenter: Ravinesh A. Kumar
Ph.D. Candidate (Medical Genetics)
Centre for Molecular Medicine and Therapeutics
Child and Family Research Institute
University of British Columbia, Canada
Abstract Mouse models of human health and disease have facilitated our understanding of the role of genes in the manifestation of human abnormal brain-behaviour development. Of particular interest to us are mice deleted for both copies of the nuclear receptor Nr2e1 ('fierce' mice), which causes cortical malformations, eye defects, short stature, post-natal growth failure, and violent behaviour in mice. In light of the high degree of molecular and functional similarities between mouse and human NR2E1, we hypothesize that humans with NR2E1 mutations will manifest with brain-behavioural abnormalities that resemble fierce mice. To test this hypothesis, we have screened for NR2E1 mutations in over 200 humans with the fierce phenotype, including patients with severe brain abnormalities and psychotic behaviour. We have identified a number of novel genetic variants, a subset of which reside in the 5' and 3' untranslated regions (UTR) of NR2E1. We are interested in determining the potential effect of these UTR variants on the structure of NR2E1, which we initially plan to test using in silico RNA secondary structure folding algorithms. The utility of such programs in assessing the role of NR2E1 RNA secondary structure in human health and disease will be discussed and debated.