For Non-Scientists

The Donnelly research group is primarily interested in studying human genetic variation and its role in human disease. One measure of genetic variation is the number of differences you expect to see when you compare the genomes of two individuals. In humans, this number is approximately 1 difference, or polymorphism, in every 1,000 bases. This may seem like a small number, but when you consider that the human genome contains approximately 3 billion basepairs, this means that two randomly selected individuals will have approximately 6 million differences across the genome! Although the majority of these differences have no effect, some contribute significantly to the observable variation within the human population. For example, your hair and eye colour are determined by the combination of differences you carry at a set of specific positions in the genome.

Genetic variation not only contributes to simple observable characteristics like hair and eye colour. It also plays a role in disease susceptibility. In the most extreme cases, a single genetic difference or variant may guarantee a person contracts a disease. Examples of this type of disease, called a Mendelian disorder, include cystic fibrosis and sickle-cell anemia. Genetic researchers have made significant progress in identifying the differences causing Mendelian disorders. Unfortunately, the majority of human diseases are not so simple. In many cases, the likelihood an individual will get a particular disease may be affected by genetic differences at possibly thousands of positions across the genome.

For diseases in which many variants are contributing, the effect of each difference is often quite small. When studying a particular disease, we must sift out the variants which contribute to susceptibility from the much larger set of differences which do not and this is a difficult task. Our research group develops sensitive statistical techniques for just this purpose. The goal of this work is to further our understanding of both the underlying mechanisms of disease and more accurate measures of an individual's susceptibility.