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.
An essay from the President: Biology for the planet
May 16, 2019
CSHL plant scientists are looking for solutions to the biggest questions in agriculture as environments are reshaped by climate change.
Genomes, justice, and the journey here
September 15, 2018
CSHL Professor W. Richard McCombie discusses genomic privacy and sequencing technology in this episode of Base Pairs.
Massive genome havoc in breast cancer is revealed
July 12, 2018
Researchers have made a highly detailed map of 20,000 structural variations in a cancer cell’s genome
Portrait of a Neuroscience Powerhouse
April 27, 2018
A relatively small neuroscience group at CSHL is having an outsized impact on a dynamic and highly competitive field
New study casts sharpest light yet on genetic mysteries of autism
October 29, 2014
Our picture of how genetic errors contribute to autism has just gotten sharper.
Putting together the genome with first-year student Maria Nattestad
May 21, 2014
Student Maria Nattestad looks to develop a fast and accurate way of putting short DNA sequences back together into the long, linear sequences.
Research sees overlap in altered genes found in schizophrenia, autism and intellectual disability
April 28, 2014
New evidence supports theory that some cases of schizophrenia and autism have malfunctions in some of the same genes are contributing to pathology.
Bread wheat’s large and complex genome is revealed
November 27, 2012
Analysis of the genome of one of world’s ‘big three’ food crops provides clues to better breeding, higher yield.
Knowing thy genome: The science and ethics of personal genome sequencing
July 10, 2012
W. Richard McCombie talks about the ethics of getting one's genome sequenced, and what consequences it may have.
‘Most comprehensive’ genetic analysis of maize plant will help raise yields, expand its range
June 1, 2012
An international research team involving 17 institutions has published the most comprehensive analysis to date of the maize genome.
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