Dr. Shiva Singh
Molecular Genetics of Complex Diseases and Phenotype
Genetic Regulatory Mechanisms & Bioinformatics
The goal of this NSERC research program is to uncover and understand genetic mechanisms underlying organization, evolution and regulation of eukaryotic genes and genomes using genetic strains of mice. The results have allowed the development of specific applied projects on methylation, gene regulation by RNA binding proteins, the effect of alcohol on gene regulation, and transpositions involving retroviral related sequences of the mammalian genome (some now funded by OMHF, SSO and CIHR). More recent genome-wide results have also allowed us to move the NSERC supported basic research from the level of the gene(s) to genomes by Affymetrix (U74v2) expression array. These results on ~25, 000 genes show that although the expression between strains in the liver is similar, the expression in the brain differs for 1 to 3.5 % of genes, depending on the genetic relatedness of the strains. This proposal deals with (1) molecular mechanisms (genetic and epigenetic) that account for strain specific difference in the global expression in the brain and (2) the development of a novel approach to functional genomics using genetic co-segregation in recombinant inbred (RI) lines of C57BL/6J and DBA/2J strains, that differ for a large number of complex phenotypes including behavior. The results will clarify the complexity of gene expression in the brain and identify candidate gene(s) for trait anxiety.