DMMC Course POPULATION GENETICS & SNP ANALYSIS

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

1700-1800 Wednesday 28 June 2006.

Plenary Lecture I - Evolution, linkage disequilibrium, and the quest for complex disease genes
Prof Lynn Jorde (Professor of Human Genetics, University of Utah, USA)

Following two decades of success in identifying genes responsible for Mendelian diseases, we now face the challenge of discovering genes that predispose to complex diseases. Linkage disequilibrium (LD) analysis has gained increasing popularity as a means of detecting genes that underlie predisposition to complex disease. In this presentation, we review the definition and basic applications of LD in disease-gene mapping. Study design issues include sample size, phenotype definition, and statistical techniques. Complex diseases, by definition, are likely to be characterized by extensive locus and allelic heterogeneity. Strategies for minimizing the effects of such heterogeneity (and thus maximizing the chances of identifying disease-causing mutations) include the use of endophenotypes, the identification of clinically defined subsets, and the use of isolated populations. Each of these strategies will be discussed and evaluated, and examples of recent success in isolating genes that underlie complex diseases (e.g., asthma, Crohn’s disease, age-related macular degeneration, type 2 diabetes) will be highlighted. In addition, the effects of evolutionary factors, such as genetic drift, natural selection, and gene flow, will be evaluated and discussed.