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Genetic Variation: We're More Different than We Thought

reviously thought.

Not only were the changes common, they also were large. "We'd find missing pieces of DNA, some a million or so nucleotides long," Scherer said. "We used to think that if you had big changes like this, then they must be involved in disease. But we are showing that we can all have these changes."

The group found nearly 16 percent of known disease-related genes in the CNVs, including genes involved in rare genetic disorders such as DiGeorge, Angelman, Williams-Beuren, and Prader-Willi syndromes, as well as those linked with schizophrenia, cataracts, spinal muscular atrophy, and atherosclerosis.

In related research published November 23, 2006, in an advance online publication in Nature Genetics, Scherer and colleagues also compared the two human genome maps—one assembled by Celera Genomics, Inc., and one from the public Human Genome Project. They found thousands of differences.

"Other people have [compared the two human genome sequences]," Scherer said, "but they found so many differences that they mostly attributed the results to error. They couldn't believe the alterations they found might be variants between the sources of DNA being analyzed."

A lot of the differences are indeed real, and they raise a red flag, he said.

Personalized genome sequencing—for individualized diagnosis, treatment, and prevention of disease—is not far off, Scherer pointed out. "The idea [behind comparing the human genome sequences] was to come up with a good understanding of what we're going to get when we do [personalized sequencing]," he explained. "This paper helps us think about how complex it will be."

In a "News and Views" article in the same issue of Nature, HHMI professor Huntington F. Willard writes, "the stage is set for global studies to explore anew…the clinical significance of human variation." Willard is director of the Institute for Genome and Science Policy at Duke Universit
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