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Cold Spring Harbor scientists devise novel, low-cost method of sifting genome’s high-value regions

Technique Opens New Horizons For Scientists Seeking Disease-Related Genes

Cold Spring Harbor, NY — Scientists at Cold Spring Harbor Laboratory (CSHL) have developed a new means of extracting and interpreting data from the human genome that is more powerful and more economical than methods currently employed. The new technology, called selective resequencing, promises to be a boon to many kinds of research, including efforts to comb vast stretches of the genome for mutant genes implicated in major diseases such as cancer and schizophrenia.

A team led by CSHL’s Gregory Hannon, Ph.D. a molecular and cell biologist, and W. Richard McCombie, Ph.D., a molecular biologist who heads the Laboratory’s gene sequencing center, sought an efficient way of separating what’s most valuable in the genome from less important stretches of genomic “code.” In all, there are over 3 billion “letters” of code in the human genome, only 2 percent of which actually instructs cells to produce proteins, the workhorses of all life processes.

CSHL’s new method is innovative because it enables genome scientists to save significant time and labor by capturing and then sequencing, or “spelling out,” genomic code culled from relatively small, focused areas—as opposed to sequencing the entire genome and only afterward honing in on areas of interest.

“In practical terms, this means that a new world of discovery is opening to scientists interested in studying the genomes of large groups of people on a comparative basis—which is a prime basis for our insights about gene mutations that cause disease,” said Dr. Hannon.

Dr. McCombie added: “By enabling scientists to target a small fraction of the genome, our method makes it possible for people with interesting ideas, to do significant work, on a modest budget. This will afford researchers the opportunity to include enough samples to conduct truly meaningful genome-wide comparative studies.”

The CSHL team’s innovation is demonstrated in a paper appearing in the November 4, 2007 online edition of Nature Genetics. A set of seven flexible, high-density microarrays, or gene-chips, were used to extract from a DNA sample only those stretches of genomic sequence that code for the manufacture of proteins. These segments, called exons, following their capture on the arrays were enriched and then sent to a state-of-the-art sequencing machine. The technique is called selective resequencing because it compares the newly obtained targeted sequences—in this case, of exons—with those of a “reference” version of the whole genome produced by the Human Genome Project.

The work was performed in cooperation with NimbleGen Systems, Inc., a genomics company based in Madison, Wisconsin.

Written by: Public Affairs | | 516-367-8455


The authors of “Genome-wide in situ exon capture for selective resequencing” include: Emily Hodges, Zhenyu Xuan, Vivekanand Balija, Melissa Kramer, Michael N. Molla, Steven W. Smith, Christina M. Middle, Matthew J. Rodesch, Thomas J. Albert, Gregory J. Hannon, and W. Richard McCombie. An advance version of the paper is available

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About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. The Meetings & Courses Program annually hosts more than 12,000 scientists. The Laboratory’s education arm also includes an academic publishing house, a graduate school and the DNA Learning Center with programs for middle and high school students and teachers. For more information, visit