McConnell, Michael J
Assistant Professor, Biochemistry and Molecular Genetics
- Postdoc, Harvard Medical School
- Postdoc, Stanford University
- BS, Zoology, North Carolina State University
- PhD, Biomedical Sciences, University of California, San Diego
The Cause and Consequence of Somatic Mosaicism in Neurons
The brain is a genetic mosaic. Neuron-to-neuron genomic differences - brought about by endogenous mobile element activity, by idiosyncratic sub-chromosomal amplifications and deletions, and by whole chromosome gains and losses are hypothesized to individualize behavioral phenotypes. To explore the causes and consequences of genetic mosaicism in neural circuits, my laboratory develops high-throughput single cell approaches and employs these approaches to study human induced pluripotent stem cell (hiPSC)-derived neurons, as well as transgenic mice. We have three immediate research goals: 1) determine if genetic mosaicism leads to somatic selection during the development of neural circuits; 2) understand how genetic mosaicism affects the performance of neural circuits; and 3) discover genes that mediate the propensity for genetic mosaicism. Moreover, altered levels of mosaicism have been associated with neurodegenerative (e.g., Ataxia-telangiectasia) and neuropsychiatric disorders (e.g., schizophrenia and Retts syndrome). A deeper understanding of these and other neurological disorders is expected from ever-increasing understanding and measurement of neuronal genomic diversity.