Most cells in the human body have two copies of each chromosome. But during the formation of reproductive cells (eggs and sperm), the copies are separated into two different cells. When that happens, a small amount of genetic material is exchanged between pairs of chromosomes. A collaboration among Memorial Sloan-Kettering molecular biologist Scott Keeney, developmental biologist Maria Jasin, and research fellow Liisa Kauppi has pinpointed sites on chromosomes where such exchanges occur before the pairs separate. The study appeared in the August 14 issue of the Proceedings of the National Academy of Sciences. [PubMed Abstract]

Chromosome separation errors, which arise more often in older eggs, can lead to disorders such as Down syndrome. To gain a better understanding of such errors, scientists must study the sites where chromosome pairs connect and exchange genetic information, a process known as recombination. The areas along the chromosomes where these connections occur are so-called hotspots for recombination.

"It's clear that connections have to happen in the right places," Dr. Keeney explained. "But we don't understand how those hotspots are determined. Is it something about the DNA sequence inside the hotspot, is it a protein that binds there, or is it sequences flanking that spot?"

To uncover these characteristics, researchers first need to pinpoint hotspots. In the new work, the scientists located two hotspots in mice. "You can't go in and manipulate the human system to understand hotspots," said Dr. Keeney. "So what you need is a model system like the mouse, where the chromosome structure is very similar."

The group looked at sections of chromosomes where they knew recombination had occurred many generations ago in lab mice. Because DNA mutates with passing generations, it was not clear whether these areas would still be hotspots, but they found that two out of the four sites studied were. This method can now be used to chart other hotspots and will allow more detailed studies of a key mechanism of chromosome biology.