Genome variation, populations and human evolution

Much of the genetic differences that can be observed between any two individuals are the result of historic events (like migration, population admixture) and chance (random segregation of alleles in large pedigrees). Buried within this large amount of non-functional variation the presence of different alleles at certain (yet unknown) loci contributes to the phenotypic differences between humans. The ultimate goal of human genetics is to identify these variants that affect specific phenotypes, such as susceptibility to common, heritable disease.

The common theme in this research line is the notion that a functional genetic variant, even with a very minor effect not easily detectable with classical genetic analyses, must have been preferentially transmitted through a large number of generations (i.e. has been subject of some kind of selection). As a result functional variants should exhibit different patterns of (dis-)similarity between populations and/or (closely related) species compared to random variation.

We address this issue both in a comparative genomic approach and studies of human population diversity. 
1-We search for genes that affect “human specific” traits by detecting positive selection in the evolutionary linage leading to our species compared to other mammalian lineages. Candidate genes obtained from this approach are tested for genetic association with a variety of human behavioral traits, such as cognitive ability, in collaboration with the Department of Biological Psychiatry.

2-Complex traits are likely to be affected by complex interactions of various genes. We search for such interactions by identifying combinations of loci that are extensively diverged between either human populations or mouse inbred lines. Relevant candidate genes/pathways are followed up in (functional) studies both in the available patient cohorts and in mice in collaboration with other participant groups of the CNCR.