W. Richard McCombie
Ph.D., University of Michigan, 1982
Over the last two decades, revolutionary improvements in DNA sequencing technology have made it faster, more accurate, and much cheaper. We are now able to sequence up to 10 trillion DNA letters in just one month. I harness these technological advancements to assemble genomes for a variety of organisms and probe the genetic basis of neurological disorders, including autism and schizophrenia, better understand cancer progression and understand the complex structures of the genomes of higher plants.
The insights of W. Richard McCombie and colleagues have led to the introduction and optimization of novel methods of high-throughput genome sequencing. His team has made it possible to catalog variation among individual organisms in a way that would have been unthinkable 10 years ago. They have brought online a new generation of Illumina sequencers and optimized their function to a level at which eight to 10 trillion DNA bases can be sequenced in a month. McCombie’s team has been involved in international efforts culminating in genome sequences for maize, rice, bread wheat—three of the world’s most important food crops. They have also had an important role in projects to sequence the flowering plant Arabidopsis thaliana (the first plant genome sequence), the fission yeast Schizosaccharomyces pombe, as well as the human genome and other important genomes. McCombie’s group is currently involved in several important projects to resequence genes in patient samples that are of special interest to human health, including DISC1 (a strong candidate gene for schizophrenia), looking for genetic variants implicated in bipolar illness and major recurrent depression. They are also looking for genes, that contribute to cancer progression using whole genome sequencing or a method called exome sequencing which they developed with Greg Hannon to look at mutations in the regions of the genome that code for proteins.
McCarthy, S. E. and Gillis, J. and Kramer, M. and Lihm, J. and Yoon, S. and Berstein, Y. and Mistry, M. and Pavlidis, P. and Solomon, R. and Ghiban, E. and Antoniou, E. and Kelleher, E. and O'Brien, C. and Donohoe, G. and Gill, M. and Morris, D. W. and McCombie, W. R. and Corvin, A. (2014) De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. Molecular Psychiatry, 19(6) pp. 652-658.
Thomson, P. A. and Parla, J. S. and McRae, A. F. and Kramer, M. and Ramakrishnan, K. and Yao, J. and Soares, D. C. and McCarthy, S. and Morris, S. W. and Cardone, L. and Cass, S. and Ghiban, E. and Hennah, W. and Evans, K. L. and Rebolini, D. and Millar, J. K. and Harris, S. E. and Starr, J. M. and MacIntyre, D. J. and McIntosh, A. M. and Watson, J. D. and Deary, I. J. and Visscher, P. M. and Blackwood, D. H. and McCombie, W. R. and Porteous, D. J. (2014) 708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: Analysis for association with psychiatric disorder and cognitive traits. Molecular Psychiatry, 19(6) pp. 668-675.
Streppel, M. M. and Lata, S. and Delabastide, M. and Montgomery, E. A. and Wang, J. S. and Canto, M. I. and Macgregor-Das, A. M. and Pai, S. and Morsink, F. H. and Offerhaus, G. J. and Antoniou, E. and Maitra, A. and McCombie, W. R. (2014) Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett's esophagus. Oncogene, 33(3) pp. 347-57.
Navin, N. E. and Kendall, J. T. and Troge, J. E. and Andrews, P. and Rodgers, L. and McIndoo, J. and Cook, K. and Stepansky, A. and Levy, D. and Esposito, D. and Muthuswamy, L. and Krasnitz, A. and McCombie, W. R. and Hicks, J. B. and Wigler, M. H. (2011) Tumour evolution inferred by single-cell sequencing. Nature, 472(7341) pp. 90-94.
Hodges, E. and Xuan, Z. Y. and Balija, V. and Kramer, M. R. and Molla, M. N. and Smith, S. W. and Middle, C. M. and Rodesch, M. J. and Albert, T. J. and Hannon, G. J. and McCombie, W. R. (2007) Genome-wide in situ exon capture for selective resequencing. Nature Genetics, 39(12) pp. 1522-7.
Research sees overlap in altered genes found in schizophrenia, autism and intellectual disability
April 28, 2014
Bread wheat’s large and complex genome is revealed
New York Plant Genomics Consortium maps evolutionary relationships, gene functions for 150 species
CSHL is part of international team that sequences the ‘chocolate’ genome
Schizophrenia, bipolar disorder and major depression have significant genetic components in their causation. We carry out both family studies in case control studies to better identify likely genetic variants contributing to these disorders. We also seek to determine the likely neurological function of the genes we identify.