May 5, 2003 HANOVER, NH – Dartmouth researchers have determined that the fruit fly Drosophila can be used for further study about why more mistakes occur during cell division as eggs become older. In humans, such errors can give rise to Down syndrome, a genetic disorder where people have one extra chromosome.
Sharon Bickel, assistant professor of biological sciences at Dartmouth, and her colleagues reported in the March 18 issue of Current Biology that fruit flies are an excellent model organism to study how age affects meiosis, the specialized cell division that gives rise to the egg and the sperm. In humans, the incidence of births of children with Down syndrome increases with the age of the mother, according to the National Down Syndrome Society.
"Age-related meiotic defects are hard to study in humans, because it's difficult to examine how this process deteriorates in females over a span of twenty years," said Bickel. "So we wanted to find out if we could utilize Drosophila as a model system to measure a similar phenomenon. Because flies are easy to grow in the lab, it's possible to look at thousands of flies and determine how frequently mistakes during meiosis are occurring."
Bickel's team specifically measured Drosophila meiotic nondisjunction, the term used to describe faulty cell division that can result in eggs that contain too many or too few chromosomes. During female meiosis in humans, nondisjunction can give rise to eggs with an extra copy of chromosome 21 and this accounts for 95 percent of all Down syndrome cases, according to the National Down Syndrome Society.
To determine whether or not meiotic errors increased in older eggs of fruit flies, the researchers devised a strategy with Drosophila to mimic the aging process that human eggs normally undergo. In humans, each female is born with all the eggs that will develop during her lifetime. As a woman ages, so do her eggs. Drosophila females, however, constantly produce and lay newly formed eggs.
"We normally feed our fruit flies yeast, and that stimulates egg development," said Bickel. "However, in these experiments, we gave them yeast for a day, to allow their eggs to mature, but then we took them off the yeast and put them on sugar for four days. Although they had a food source that kept them healthy, egg-laying was inhibited and this caused the eggs to "age" within the body of the female."
To assess whether errors occurred during the meiotic cell divisions of the egg, the researchers used genetic markers that affect the fly's body color and shape of the eye.
"After the egg is fertilized and grows into an adult, we can use these markers to tell whether or not meiotic nondisjunction happened in the egg," said Bickel. "With the strain of flies that we used, we saw a dramatic increase in nondisjunction of aged versus non-aged eggs."
Bickel explained that, in humans, there may be a back-up system that functions in young eggs to prevent these meiotic mistakes. However, one theory is that in older eggs, some component of the system has deteriorated with time and no longer works properly.
"This is a very initial finding," says Bickel. "We've simply discovered that fruit flies, under these conditions, can mimic what happens in humans. There's a whole set of experiments we can do now to start to find out what exactly is going wrong. It really opens up the field."
The other authors on the paper are Charlotte A. Jeffreys, laboratory technician in the department of Biological Sciences, and Peter S. Burrage, a 2000 Dartmouth graduate who is now an MD/Ph.D. student at Dartmouth. This study was initiated with funds from the Hitchcock Foundation and continued with grants from the March of Dimes and the National Institutes of Health.
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