Studies look into how DNA crossovers can drive healthy or abnormal sperm, egg cell division

In the famous words of movie character Forrest Gump, “Life is like a box of chocolates; you never know what you’re gonna get.”

The same principle applies to human genetics. When the body forms sperm or egg cells in a special type of cell division called meiosis, our DNA mixes and matches in seemingly infinite and unpredictable combinations.

Later, when just two of the great variety of sperm and egg cells meet, they produce children who are different from their parents. Meiosis would go terribly wrong without crossovers: the swapping of DNA segments between closely aligned pairs of chromosomes, one inherited from each parent. Faulty crossover formation can leave cells with too many or too few chromosomes, known as aneuploidy. Since aneuploidy in turn can lead to infertility, miscarriages and conditions such as Down syndrome, learning how crossovers are regulated is key to understanding human reproduction and improving reproductive health.

In a study published in the journal Nature, researchers from Harvard Medical School conducted simultaneous analyses of crossovers and aneuploidy on all chromosomes in more than 30,000 human sperm cells used a new genome-wide sequencing tool. The findings help answer a longstanding question about why and how crossover rates vary across sperm cells and across people.

A second study, from another Harvard-based research team, looked at meiosis in developing worm egg cells, and helps explain why crossovers occur more often in some locations along chromosomes than in others. The team found that crossovers are likelier to go wrong at the centers or extreme ends of chromosomes, suggesting that egg cells minimize crossovers in those areas while allowing them in more reliable locations.

This study, from the lab of Monica Colaiácovo, professor of genetics at Harvard Medical School, were published in Current Biology. “It’s terrific to see how findings in male and female meiosis and in different species can complement and inform each other,” said Colaiácovo.

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