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Cataloging the Structural Variations in Human Genetics

n dollar question is what is the genetic basis of diseases like diabetes, hypertension, and high cholesterol levels? says Eichler. We know there is a genetic factor, but what is the role of single base pair changes versus structural changes?

The project Eichler and his colleagues describe in their paper will help answer this question. Using DNA from 62 people who were studied as part of the International HapMap Project, they are creating bacterial libraries of DNA segments for each person. The ends of the segments are then sequenced to uncover evidence of structural variation. Whenever such evidence is found, the entire DNA segment is sequenced to catalog all of the genetic differences between the segment and the reference sequence.

The result, says Eichler, will be a tool that geneticists can use to associate structural variation with particular diseases. It might be that if I have an extra copy of gene A, my threshold for disease X may be higher or lower. Geneticists will then be able to test, or genotype, large numbers of individuals who have a particular disease to look for structural variants that they have in common. If a given variant is contributing to a disease, it will occur at a higher frequency in people with the disease.

Knowing about structural variation in the human genome will also allow geneticists to analyze single-base-pair changes more effectively, according to Aravinda Chakravarti, a geneticist at The Johns Hopkins University School of Medicine who was not a coauthor of the paper. We have to look at structural variants from a different perspective, because they are adding or subtracting something from the genome, Chakravarti says. By understanding the patterns of both structural variants and single-base-pair changes in the population, we'll learn a lot. To use both kinds of information in tandem, Eichler and his colleagues plan to incorporate the structural information they gather into existing datab
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