Population genetics, molecular evolution, and phylogenetic reconstruction are a continuum of disciplines that provide different perspectives on some of the more interesting questions of human genetic disease, including cancer. Major advances in both the theory and the application of these disciplines are now possible with the exquisitely detailed understanding of human and other genomes that is emerging. Research objectives of this project primarily concern the development and application of demographic, genetic, and phylogenetic analyses. In particular, these modes of analysis are being used to underpin novel gene mapping strategies that range from the identification and localization of disease and disease susceptibility genes to studies mapping the critical functional and disease-related motifs within alleles of the human major histocompatibility complex. These projects are interrelated, and share the common goal of inferring historical patterns of association and the mechanisms that maintain or destroy them. Only then will it be possible to determine whether observed genic or allelic associations are truly functional (e.g., disease related) or simply a consequence of historic population genetic or evolutionary processes.
