Most complex disorders are influenced by a mix genetic and environmental factors. Environmental factors can cause changes to gene expression in the body through epigenetic mechanisms that control gene activity. The Gregg lab has discovered novel epigenetic effects in the brain and in other tissues of the body that differentially impact the expression of maternally versus paternally inherited gene copies (or alleles). We have uncovered many different forms of these effects. Canonical genomic imprinting involves complete silencing of the maternal or paternal allele. Noncanonical imprinting involves partial or cell-type specific silencing of one parent’s allele. These two mechanisms constitute heritable maternal and paternal influences on gene expression in offspring. Recently, we further discovered allele co-expression effects, differential allele expression effects and antagonistic allele expression effects in the brain. Our research reveals that diverse epigenetic effects shape the expression of maternal and paternal alleles in the brain.
Since most genetic mutations are heterozygous, meaning only one gene copy is impacted, a potential implication of our findings is that epigenetic mechanisms may silence one gene copy such that some cells in the body only express a mutated copy and the healthy backup copy is silent. We are testing the hypothesis that human brain disorders and other diseases arise, in part, because of the existence of cells that preferentially express a mutated maternal or paternal gene copy. Further, we are investigating the normal biological function of the these epigenetic effects and applications for disease diagnostics and therapy.