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Media Contacts:
Dr. Trudy MacKay, 919/515-5810 or [email protected]
Tim Lucas, News Services, 919/515-3470 or [email protected]
Feb. 11, 1998
Study Yields New Clues on Genetics of Lifespan, Other Complex Traits
EMBARGOED FOR RELEASE AT 3 P.M., MONDAY, FEB. 16
Most people think there's little they could learn from a fruit fly.
But Dr. Trudy Mackay knows better. In her research laboratory at North Carolina State University, Mackay studies the genetic basis of complex traits in fruit flies, with the aim of applying that knowledge to better understanding human genetics.
Her findings -- including evidence that both gender and environment can affect gene expression -- are giving medical researchers new insight into the genetic mechanisms responsible for complex traits such as longevity, high blood pressure and heart disease in humans.
Complex traits are caused by the interaction of several genes. Unraveling the gene combinations that affect the expression of these traits has long been a challenge for researchers.
Mackay will present an overview of her work, "The Genetic Basis of Quantitative Variation: Lessons From Drosophila," at 3 p.m. Monday, Feb. 16, at the 1998 annual meeting of the American Association for the Advancement of Science (AAAS) in Philadelphia, the year's most prestigious scientific conference. She is one of five NC State scientists invited to present their recent research findings at the AAAS convention.
One of Mackay's most intriguing discoveries is that gene expression for longevity in fruit flies is sex-specific. "We found, quite unexpectedly, that the quantitative trait loci affecting lifespan are different for males than for females," she says. "It's the same gene, but it is expressed differently in each sex."
The finding, which is consistent with research conducted on the expression of complex traits in other species, has serious implications for medical research, she believes, because it suggests that scientists need to pay more attention to the size and sexual makeup of their experimental populations, and how results from studies involving both sexes are interpreted.
"Through numerous studies, we know there are parallels between the genetics of complex traits in fruit flies and in humans; so much so that if we find something to be true in fruit flies, it also is likely true in humans," Mackay says. "Scientists increasingly tend to use smaller experimental populations to keep costs and paperwork in line. But given what we've found about the sex-specific differences in gene expression of complex traits, the opposite strategy may be called for. Researchers may actually have to double the size of their experimental population to get accurate results for both sexes," she says.
Lumping data from male and female subjects together indisciminantly also is a bad idea, she believes, because it may obscure results that are important for one sex but not the other. "If a study does not find a significant result, it may be because the researchers failed to take the sex-specific differences in the genes involved into consideration."
In related studies, Mackay and her associates also have shown that gene expression of complex traits is affected by environment. "We divided a population of fruit flies into four equal groups and subjected each group to a different environment. The genes affecting each group's longevity were totally different. We were seeing action in completely different regions of the chromosomes."
Mackay's research on the genetic basis of complex traits has been published in many of the world's most prestigious peer-reviewed journals, including Science and the Proceedings of the National Academy of Sciences. At NC State, she holds the William Neal Reynolds Professorship in genetics.
In addition to its relevance to human research, her work also has broad implications in agricultural research, especially livestock and crop breeding.
"Milk production, disease resistance and yield are all complex traits," she says. "To successfully breed these traits into a line, scientists need to better understand the underlying mechanisms that regulate them."
-- lucas --
Editor's Note: An abstract from Dr. Mackay's AAAS presentation follows.
"The Genetic Basis of Quantitative Variation: Lessons from Drosophila" Dr. Trudy F.C. Mackay North Carolina State University presented at the 1998 annual meeting of the American Association for the Advancement of Science
ABSTRACT: Recent analyses of the genetic basis of quantitative variation for Drosophila bristle number have shown that many of the loci responsible for variation in bristle number are candidate genes that affect bristle development. Most of the standing variation in bristle number may be caused by alleles at a few of these loci with large homozygous effects, and that segregate at intermediate frequencies. Segregating alleles have appreciable sex-specific and environment-specific effects, and interact epistatically. These properties may contribute to the maintenance of variation for quantitative traits. Molecular polymorphisms associated with phenotypic variation in bristle number are in non-coding regions of the candidate loci, suggesting that variation in regulation of gene expression causes quantitative differences in phenotypes.
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