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Fruit Flies, Mice and How Their Genetic Codes Can Help You

The Research Triangle is ground zero for new genomics research and resources that hold the promise to speed new discoveries in everything from pest control to personalized medicine.

In the past two weeks, NC State geneticists Trudy Mackay and David Threadgill, working with collaborators from across the globe, have published landmark scientific papers and made available new resources that will make it easier for researchers to tease out the links between an organism’s genetic blueprint and its behavior or traits. These blueprints for behavior in fruit flies and mice will in turn make it easier for researchers to develop new cures and treatments for a wide range of human diseases.

These new resources are akin to reference libraries that are freely available to researchers studying everything from cancer to cholesterol levels to aggression. These reference libraries aren’t actual books, but instead are special fruit flies and mice, along with their genetic sequence data.

Lord of the Flies

Mackay’s work on fruit flies, published two weeks ago in the granddaddy of science journals, Nature, described one of the new reference libraries – the Drosophila melanogaster Reference Panel, or DGRP. Mackay, William Neal Reynolds and Distinguished University Professor of Genetics and a member of the National Academy of Sciences, says that the DGRP contains 192 lines of fruit flies that differ enormously in their genetic variation but are identical within each line, along with their genetic sequence data.

Dr. Trudy Mackay

“Until now, we had the information necessary to understand what makes a fruit fly different from, say, a mosquito,” Mackay says. “Now we understand the genetic differences responsible for individual variation, or why one strain of flies lives longer or is more aggressive than another strain.”

What can a fruit fly – no one’s idea of a heavyweight – tell you about human aggression? Imagine studying flies that are bred to be really aggressive. Aggression is a quantitative, or complex, trait, so lots of genes are involved in governing the aggressive behavior. Mackay and Dr. Robert Anholt, William Neal Reynolds Distinguished Professor of Biology at NC State, have discovered that hyper-aggressive flies have smaller brain portions than normal flies, and that some hyper-aggressive flies could not be calmed by mood-altering drugs like lithium.

These findings may help researchers predict which genes are involved in human aggression as well as how those genes interact in different populations – think of hormonal teenage boys or Alzheimer’s patients who suddenly become more aggressive, for instance.

The Nature paper showed that, in general, many genes were associated with three quantitative traits studied in fruit flies – resistance to starvation stress, chill coma recovery time and startle response – and that the effects of these genes were quite large.

Mighty Mice

It’s taken more than a decade to come to fruition, but the new resource – a reference library of mice and their genetic information called the Collaborative Cross (CC) – developed by Threadgill and his collaborators could pave the way to faster human health discoveries and transform the ways people battle and prevent disease.

Dr. David Threadgill

In 15 scientific papers published last week in the journals Genetics and G3:Genes/Genomes/Genetics, researchers from NC State, the University of North Carolina at Chapel Hill, The Jackson Laboratory and other universities and labs across the globe highlight the new resource – one that is, again, freely available to researchers anywhere in the world – and describe how the mice are already leading to advances in human biology.

The secret to these special CC mice? They have much more genetic variation than normal lab mice, and thus more closely mirror the genetic complexity found in humans.

“If you can’t mimic the genetic variation in people, you can’t necessarily use mouse findings to understand more about human disease,” says Threadgill, professor and department head of genetics at NC State who originally proposed the idea for the CC project a decade ago and who serves as one of the project leaders. He is also a member of the UNC’s Lineberger Comprehensive Cancer Center.

In one of the 15 papers, Threadgill and corresponding author Dr. Francis S. Collins, director of the National Institutes of Health, use the CC mice to identify key genes involved in red and white blood cell counts and red blood cell volume. These hematological parameters are important indicators of health and disease.

So when fruit flies weave their way around your kitchen fruit basket and mice scamper across your kitchen floor, think about the contributions their kin are making to science before you attack them with a swatter or a broom.

These critters may one day save your life.

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