INVITED AND SPECIAL SESSIONS
Wednesday, October 26
8:00 PM-10:00 PM
Concurrent Invited Sessions I (12-18)
SESSION 16 - Polymorphic and Disease-Related Large-Scale Genomic Rearrangements: Evolution, Population Substructures, Genomic Architecture and Diagnostics
Hall E
Co-Moderators: David L. Nelson, Baylor College of Medicine, Houston, TX; and Swaroop Aradhya, Stanford University, CA
The human genome contains numerous locally duplicated regions (segmental duplications) that are often found to be susceptible to rearrangement. Some of these events have been found associated with genetic disorders. The frequency of diseases arising from segmental duplications has been estimated to be 1 in 1,000 births. Some duplicated sequences also exhibit a striking capacity to undergo rearrangement in both germline and somatic tissues. The majority of segmental duplications have not been associated with genetic disorders; however, an increasing number are now known to be polymorphic in the human population. Microarray analyses have demonstrated polymorphic variation in the content of segmental duplication. There is substantial variety in the lengths and composition of duplications, with unique features among groups. A common finding, however, is that most expansions of these repeats occurred in the higher primate lineage. They have been stably propagated due to inherent properties of the genome. For example, gene conversion and recombination have maintained a high degree of sequence similarity within several duplications. As a result, it has proven difficult to establish diagnostic methods when these regions are associated with disease. Segmental duplications in pericentromeric or subtelomeric regions have characteristic qualities relevant to the formation of cytogenetic abnormalities. However, novel cytogenetic and microarray methods have now been developed to detect disease-related rearrangements at a variety of regions. While the Human Genome Project allowed substantial progress in understanding the nature of segmental duplication in humans, numerous questions still remain concerning the evolution, propagation, and stability of these sequences. Further investigation of these large-scale rearrangement-prone sequences is important with respect to human disease, polymorphism, population, and evolutionary studies, and diagnostics.
8:00 PM Evolution of segmental duplications in the human genome and related diseases. Evan Eichler, University of Washington, Seattle.
8:30 PM Germline and somatic genomic rearrangements and human disease. James R. Lupski, Baylor College of Medicine, Houston, TX.
9:00 PM Pericentromeric and subtelomeric repeat sequences and cytogenetic abnormalities. David H. Ledbetter, Emory University, Atlanta, GA.
9:30 PM Studies of human genetic variation and disease by high-resolution analysis of gene copy number. Jonathan Sebat, Cold Spring Harbor Laboratories, NY.
