Which DNA changes contribute to meaningful differences between individuals such as disease state or disease risk, and which are of little consequence?

Identifying disease mutations and functional variants
A major focus of research at the HGU and IGMM is the identification of loci and ultimately specific polymorphisms that contribute to disease risk. Current genotyping based association studies depend on just a few alleles being responsible for most of the population risk contributed by a locus. In such studies it is widely believed that comparative genomics can help with the identification of functional variation and the detection of selection add power to those analyses by removing the confounding influence of mutation rate variation. However, it is becoming increasingly apparent that much of the genetic risk for the most common human diseases such as heart disease, diabetes, cancer and mental illness lies not in common variants of individually small effect, but in rarer variants of greater effect.

We are adapting commonly used statistical frameworks from the field molecular evolution to identify genes harbouring these rare variants based on case-control and case-only sequencing projects. With some modifications we are also adapting these approaches to study the selection pressures acting during the development and progression of cancer