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Researchers uncover surprising degree of large-scale variation in the human genome

A new study by Michael Wigler's group at Cold Spring Harbor Laboratory has revealed surprising differences in the DNA of normal cells from different people.

The study, which appears this week in the journal Science, used a powerful new DNA profiling technique, originally developed by Wigler's group, called ROMA (representational oligonucleotide microarray analysis). The technique was initially developed to detect the genetic differences between normal cells and cancer cells. This application of ROMA has revealed several chromosomal amplifications (excess copies of DNA segments) and deletions (missing DNA segments) associated with a variety of human cancers in individual patients (see http://www.cshl.edu/public/releases/revealing.html ).

However, in the course of that work, the researchers were greatly surprised to have detected several large-scale, previously unidentified differences in human DNA when they carried out "normal to normal" control comparisons of DNA from different individuals.

In the new study, Wigler's group created an extensive profile of such genetic variation in normal human DNA. The researchers sampled blood and multiple tissues from 20 individuals from a variety of geographic backgrounds. Differences in the chromosomal DNA purified from these samples were detected by ROMA.

The researchers detected 76 large-scale "copy number polymorphisms" or CNPs. Among the 70 genes associated with the newly-identified CNPs were those involved in Cohen syndrome and neurological development, and others implicated in leukemia and drug resistant forms of breast cancer. In addition, some CNPs identified genes with known influence on 'normal' human phenotypes including oneneuropeptide-Y4 receptorthat is directly involved in the regulation of food intake and body weight.

According to the study, a relationship between CNPs a
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Contact: Peter Sherwood
sherwood@cshl.edu
516-367-6947
Cold Spring Harbor Laboratory
22-Jul-2004


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