The rockefeller university

Event Details

Type

Special Seminar Series

Speaker(s)

Guy Rouleau, M.D., Ph.D., director, Montreal Neurological Institute and Hospital; Wilder Penfield Chair in Neuroscience and full professor, department of neurology and neurosurgery, McGill University

Speaker bio(s)

Schizophrenia and autism spectrum disorders are common, devastating and poorly treated brain disorders. Dr. Rouleau's lab hypothesizes that a significant fraction of schizophrenia and autism cases result from penetrant de novo mutations in genes, particularly those coding for synaptic proteins. The lab's initial strategy was to re-sequence genes encoding synaptic proteins in patients and test their parents to identify de novo mutations, followed by functional validation of variants in zebrafish, Drosophila or mouse hippocampal cell models. They identified 5,079 potentially synaptic genes based on published studies and databases. The lab then PCR amplified and sequenced all coding exons of a prioritized subset of these genes from 143 schizophrenia and 142 autism spectrum disorder probands. In the first 402 genes they identified >6,000 variants, of which >4,000 are novel; 28 were de novo variants, of which in 15 were confirmed in blood DNA. These data suggest that there is an excess of de novo mutations in schizophrenia and autism. Some of the genes for which de novo variants were found were tested for functional effects using the different animal and cell models. Dr. Rouleau's lab identified several new genes associated with these diseases (ex. SHANK3, IL1RAPL1). They then interrogated all genes for de novo mutations in a small set of schizophrenia parents using exome capture and sequencing using Illumina or ABI high throughput sequencing. Using this method the lab confirmed that there is a higher than expected de novo mutation rate in schizophrenia. They propose that de novo mutations may explain part of the missing heritability in schizophrenia and autism. The lab is now working to identify factors that may affect the rate of de novo mutations. Preliminary data using monozygotic twins suggests that paternal age affects the rate of de novo germline point mutations and small indels, but not copy number variants or somatic de novo mutations. Further work is underway to look at the effects of genetic background and environmental factors in the genesis of de novo mutations.

Dr. Rouleau received his M.D. from the University of Ottawa in 1980 and his Ph.D. in genetics from Harvard University in 1989. He completed his internship in internal medicine at Montreal General Hospital and his residency in neurology at the Montreal Neurological Hospital of McGill University. Dr. Rouleau completed postgraduate research work in neuroscience at the Montreal Neurological Institute, McGill University and Massachusetts General Hospital. He has been on the faculty of McGill University since 1989, where he is now full professor in the department of neurology and neurosurgery and holds the Wilder Penfield Chair in Neuroscience. Dr. Rouleau became the director of the Montreal Neurological Institute and Hospital in 2013. He was previously a tenured professor and chairholder at the University of Montreal, as well as the director of the network of applied genetic medicine at Fonds de la recherche en santé du Québec. Dr. Rouleau is the recipient of a number of awards and honors, including the Barbeau Memorial Prize for research in Neuroscience from the Canadian Neurological Society, the Career Prize from the Stars Foundation and the Wilder-Penfield Prize from the Government of Quebec. He is on the editorial boards of Neurology of Disease and Annal of Human Genetics.

Open to

Public

Reception

Refreshments, 3:45 p.m. - 4:00 p.m., Lower Level Greenberg Building (CRC)

Contact

Jill Benz

Phone

(212) 327-7244

Sponsor

Jill Benz
(212) 327-7244
benzj@rockefeller.edu