Does increasing paternal age causes CNVs that are deleterious to develop in spermatogonia?

Standing on a spiral staircase inspired by the helical structure of DNA, Charles Lee (right) and John Iafrate discuss the surprising gaps they found in the human genome. The gaps may explain some of the differences in human nature, as well as to identify people who are prone to certain diseases, including cancer. (Staff photo Stephanie Mitchell/Harvard News Office)


Surprising variations discovered in human genomes
Unexpected DNA losses and gains found
By William J. Cromie
Harvard News Office

Contrary to expectations, a startling number of large variations have been found in the human genome. The genetic blueprints for humans were thought to be 99.9 percent similar, but researchers at Harvard Medical School and the University of Toronto in Canada have accidentally discovered large chunks of missing or added DNA in normal, healthy people.

"We were extraordinarily surprised to see that some people have so much more or less DNA," says Charles Lee, a geneticist and assistant professor at Harvard. "We're very excited about this. It could explain differences in human nature, and help us to identify people who are more prone to certain diseases."

Working at Brigham and Women's Hospital in Boston, Lee and his colleagues were comparing genomes of a group of unrelated people. The idea is to establish a template with which to compare the genomes of patients. Any differences found in patients might be related to specific diseases.

"We expected to see flat lines when we matched the genomes of healthy people, denoting a lack of difference at various regions throughout the human genome," Lee recalls. "But we kept seeing blips. At first, we thought this was simply static in our equipment. But the same blips kept showing up in different people."

About this time, Lee was invited to give a talk at the University of Toronto. In the talk, he didn't mention what he'd found because he was not sure what it meant. But the variations came up during a conversation with Stephen Scherer and his colleagues at The Hospital for Sick Children in Toronto. They admitted that they were seeing similar blips.

The two groups decided to collaborate by pooling the blip data they had on different sets of patients. "It turned out to be a very fruitful collaboration," Lee comments. "It is helping us to