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.
Parla, J. S. and Iossifov, I. and Grabill, I. and Spector, M. S. and Kramer, M. and McCombie, W. R. (2011) A comparative analysis of exome capture. Genome Biology 12(9) pp. R97.
Molaro, A. and Hodges, E. and Fang, F. and Song, Q. and McCombie, W. R. and Hannon, G. J. and Smith, A. D. (2011) Sperm Methylation Profiles Reveal Features of Epigenetic Inheritance and Evolution in Primates. Cell 146(6) pp. 1029-1041.
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.
Lander, E. S. and Linton, L. M. and Birren, B. and Nusbaum, C. and Zody, M. C. and Baldwin, J. and Devon, K. and Dewar, K. and Doyle, M. and Fitzhugh, W. and Funke, R. and Gage, D. and Harris, K. and Heaford, A. and Howland, J. and Kann, L. and Lehoczky, J. and Levine, R. and McEwan, P. and McKernan, K. and Meldrim, J. and Mesirov, J. P. and Miranda, C. and Morris, W. and Naylor, J. and Raymond, C. and Rosetti, M. and Santos, R. and Sheridan, A. and Sougnez, C. and Stange-Thomann, N. and Stojanovic, N. and Subramanian, A. and Wyman, D. and Rogers, J. and Sulston, J. and Ainscough, R. and Beck, S. and Bentley, D. and Burton, J. and Clee, C. and Carter, N. and Coulson, A. and Deadman, R. and Deloukas, P. and Dunham, A. and Dunham, I. and Durbin, R. and French, L. and Grafham, D. and Gregory, S. and Hubbard, T. and Humphray, S. and Hunt, A. and Jones, M. and Lloyd, C. and McMurray, A. and Matthews, L. and Mercer, S. and Milne, S. and Mullikin, J. C. and Mungall, A. and Plumb, R. and Ross, M. and Shownkeen, R. and Sims, S. and Waterston, R. H. and Wilson, R. K. and Hillier, L. W. and McPherson, J. D. and Marra, M. A. and Mardis, E. R. and Fulton, L. A. and Chinwalla, A. T. and Pepin, K. H. and Gish, W. R. and Chissoe, S. L. and Wendl, M. C. and Delehaunty, K. D. and Miner, T. L. and Delehaunty, A. and Kramer, J. B. and Cook, L. L. and Fulton, R. S. and Johnson, D. L. and Minx, P. J. and Clifton, S. W. and Hawkins, T. and Branscomb, E. and Predki, P. and Richardson, P. and Wenning, S. and Slezak, T. and Doggett, N. and Cheng, J. F. and Olsen, A. and Lucas, S. and Elkin, C. and Uberbacher, E. and Frazier, M. (2001) Initial sequencing and analysis of the human genome. Nature 409(6822) pp. 860-921.Additional materials of the author at
CSHL Institutional Repository
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