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Volume 23 / No. 1 / 2012
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Flies and Humans: Looking into Genetic Variation in Populations

Andrew G. Clark, Molecular Biology and Genetics Clark
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How do differences in DNA sequences in a population produce variability in complex traits? We hope to learn basic principles of this correspondence in flies and apply those to understand variation in disease risk in people.

From Flies to Humans

As an undergraduate I had the great fortune to be working in the lab where Margaret Kidwell was doing her early work that led to the discovery of the P element, the first transposable element used to manipulate the fly genome. I started out in the laboratory working with fruit flies, Drosophila melanogaster, because it was easy to set up populations that tested population genetic models. Drosophila also happens to be a terrific model organism for understanding many basic mechanisms in genetics and cell biology.

Years later, when I established my own research lab to study the population genetics of Drosophila, my group became interested in the problem of modeling fat storage in flies. We wanted to be able to predict—given information about the genetic composition of flies with diverse genetic backgrounds—which lines of flies would store more lipid. This work attracted the attention of researchers in human cardiovascular disease, since they were trying to model the genetic basis for differences in cholesterol deposition in blood vessels. So I got involved in this collaboration starting in 1996, and it has continued to this day.

Working with medical collaborators about 10 years ago, we sequenced a specific set of genes in the reverse cholesterol transport pathway of several people. These analyses really opened researchers’ eyes to the abundance and complexity of genetic variation in human genes. Among a sample of 71 normal people, there were 88 DNA sequence differences in just one gene!

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