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.
Genomes, justice, and the journey here
September 15, 2018
Base Pairs podcast Mail-order genetic testing—more accurately known as genotyping—has become a growing trend. Simply spit into a tube, and companies claim they can tell you about where your family comes from, what conditions and illnesses you might be predisposed to, and what your family tree looks like. One of the more surprising uses of...
Massive genome havoc in breast cancer is revealed
July 12, 2018
Cold Spring Harbor, NY — In cancer cells, genetic errors wreak havoc. Misspelled genes, as well as structural variations—larger-scale rearrangements of DNA that can encompass large chunks of chromosomes—disturb carefully balanced mechanisms that have evolved to regulate cell growth. Genes that are normally silent are massively activated and mutant proteins are formed. These and other...
Portrait of a Neuroscience Powerhouse
April 27, 2018
At noon every Tuesday from September through June, scenes from a revolution in neuroscience are playing out at Cold Spring Harbor Laboratory. Week after week, over 100 scientists cram themselves into a ground-floor meeting room in the Beckman Laboratory. It’s standing-room only as everyone in the Neuroscience Program settles in to hear details of the...
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. Cold Spring Harbor, NY — Our picture of how genetic errors contribute to autism has just gotten sharper. The latest series of clarifications in what, in its totality, is a very complex puzzle, emerges from new research published in Nature today by...
Putting together the genome with first-year student Maria Nattestad
May 21, 2014
In 1990, the effort to sequence the human genome began, led, in part, by Cold Spring Harbor Laboratory’s then-director Jim Watson. Scientists anticipated the project would reveal about 100,000 genes occupying the 3.3 billion bases of DNA. The human genome sequence would help us understand and treat thousands of diseases with genetic contributions. Sequencing cost between $2 and...
Research sees overlap in altered genes found in schizophrenia, autism and intellectual disability
April 28, 2014
Dublin, Ireland and Cold Spring Harbor, NY — In research published today in Molecular Psychiatry, a multinational team of scientists presents new evidence supporting the theory that in at least some cases of schizophrenia, autism and intellectual disability (ID), malfunctions in some of the same genes are contributing to pathology. The team, the product of...
Bread wheat’s large and complex genome is revealed
November 27, 2012
Cold Spring Harbor, NY — Bread wheat (Triticum aestivum) is one of the “big three” globally important crops, accounting for 20% of the calories consumed by people. Fully 35% of the world’s 7 billion people depend on this staple crop for survival. Now an international team of scientists, including a group from Cold Spring Harbor...
Knowing thy genome: The science and ethics of personal genome sequencing
July 10, 2012
LabDish blog Until not too long ago, asking “Who am I?” of oneself often meant undertaking a voyage of self-discovery either through travel to a faraway land or through time-limited visits to a therapist’s couch. We now live in an era that offers a third, possibly cheaper armchair option. For less than the price of...
‘Most comprehensive’ genetic analysis of maize plant will help raise yields, expand its range
June 1, 2012
Cold Spring Harbor, NY and Washington, DC — An international research team involving 17 institutions including Cold Spring Harbor Laboratory has published the most comprehensive analysis to date of the maize genome. It is an achievement that substantially increases scientists’ understanding of differences across related but different species of the plant, which most North Americans call corn,...
CSHL is part of international team that sequences genomes of the “Heinz” tomato & its wild ancestor
May 25, 2012
Wild tomato genome, sequenced at CSHL, provides basis for understanding how the domesticated variety evolved and adapted to new environments—knowledge that can help improve worldwide tomato production Cold Spring Harbor, NY — A team of scientists from Cold Spring Harbor Laboratory (CSHL) and their colleagues in the Tomato Genomics Consortium (TGC) have succeeded in a...
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
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