DOE Human Genome Program Contractor-Grantee Workshop VIII
February 27-March 2, 2000  Santa Fe, NM

4. A Tale of Three Loci

Lee Rowen, Anup Madan, Shizhen Qin, and Lee Hood

Multimegabase Sequencing Center, University of Washington, Seattle, WA 98195 and Institute for Systems Biology, Seattle, WA

leerowen@u.washington.edu

One of the fascinating results of large-scale sequencing is the revelation of vastly different types of genomic landscapes. Based on our accumulation of finished sequence over long contiguous stretches of the genome, we plan to present data analyses pertaining to three of these landscapes:

A) The human and mouse beta T cell receptor loci, which exemplify the rapid evolution of a multigene family. Here, genes are embedded in long repeats which are added to or deleted from the genome via unequal cross-over. In this regard, human and mouse have undergone somewhat different evolutionary paths.

B) The human and mouse major histocompatibility complex class III regions, which exemplify high gene density (> 15% coding sequence). Here, the orthologous relationship between human and mouse is highly conserved. This landscape raises interesting questions about gene regulation and why it is that genes with apparently unrelated functions might be so closely spaced.

C) The human neurexin III gene on chromosome 14, which exemplifies a large-intron gene that spans over a megabase. Neurexins are noteworthy for their large number of alternative splice forms and their differential expression in neurons, depending supposedly on the alternative splices.

The notion of genomic landscapes provides a framework for thinking beyond individual genes to the organization of the genome as a whole and how this organization bears on different types of function for individual genes and gene families.