the-aps.org>meetings>eb

Comparative Genomics: Linking Noncoding DNA to Biology and Disease
Sponsored by APS Physiological Genomics Group

The large fraction of the human genome that does not code for proteins harbors DNA sequences that are critical for the proper temporal, spatial and quantitative expression of genes, mediate genomic architecture and organization, and are thought to represent an important substrate for the molecular evolution that shaped our genome. Thus, sequence variations in these noncoding DNA elements are likely to impact a broad range of biological processes and be responsible for phenotypical differences among humans, including the predisposition to diseases. The in silico identification of these discrete noncoding DNA sequences buried in the human genome, the experimental characterization of their functional properties, and their roles in disease processes were greatly facilitated by our ability to compare genomes from various species, and will be the main focus of this symposium. Topics include the presentation of bioinformatics tools designed to identify functional noncoding DNA elements in the human genome, both from the premise that several of these elements are shared with other species and have been conserved throughout evolution and also that other elements are likely to be unique to primates and/or humans. Experimental designs to empirically test noncoding elements for biological functions will be presented, focusing on the applications and pitfalls of each strategy and animal models used. Particular attention will be given to the identification and functional characterization of rapidly evolving noncoding DNA, likely to be involved in the key speciation events that lead to the evolution of humans. Finally, using a compilation of the strategies presented in the symposium, the genetic determinants of Hirschsprung’s disease will be discussed and the discovery of sequence variations in noncoding DNA leading to this disease will be illustrated.