DMMC Course POPULATION GENETICS & SNP ANALYSIS

Durkan Lecture Theatre, Institute of Molecular Medicine, TCD, St James's Hospital

1610-1700 Wednesday 28 June 2006.

Applications of human population genomics: Mapping complex disease genes
Prof Mark Shriver (Associate Professor of Biological Anthropology, Pennsylvania State University, USA)

Human genetic variation is increasingly being recognized as an important source of both statistical power and potential confounding in complex disease studies. There are several aspects of genetic variation that help us to understand how these two factors might adversely and/or beneficially affect study designs. The first is the question of which are the important "axes of ancestry" across which there is genetic variation within the population (or more often in large epidemiological studies, metapopulation) to be studied. For many contemporary ethnically defined "populations" there is variability in individual ancestry levels brought about through the process of genetic admixture – the intermixture between previously isolated populations and geographic heterogeneity. Such variation in individual admixture can be used in a number of ways to study the genetics of complex diseases (Halder and Shriver, 2003). These include testing for ancestry/phenotype correlations and analyses to determine the ultimate causes of such associations. Second, it is important adopt a new paradigm of the human genomic evolution – the population genomic model. An important observation in this model is that the genome does not have a single evolutionary history. Evolution has not affected all genomic regions to the same extent (Shriver et al., 2004) and this fact also has important implications on how we structure complex studies particularly in relation to population stratification. The practical application of admixture gene mapping and phenotype investigation highlight the general utility of an understanding of the evolutionary histories of human populations with reference to the extent to which particular genomic regions have evolved.

References

Halder, I. & Shriver, M.D. (2003). Measuring and using admixture to study the genetics of complex diseases. Hum Genomics. 1, 52-62. PubMed Entry

Shriver, M.D., et al. (2004). The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs. Hum Genomics. 1, 274-286. PubMed Entry