This segment will first introduce the issues and problems involved in genome analysis by comparing information ascertained about genomes across species. The discussion will then focus on state-of-the-art technologies for mapping and sequencing genomes, e.g., cytogenetic analyses, physical mapping, genetic linkage analyses of simple and complex disorders and DNA sequencing. Finally, we will apply these techniques to examine genetic variation and close with a discussion of emerging technologies designed to analyze gene functions across whole genomes. This section will lead into the following segments that employ strategies for functional analyses using protein homology and classical genetic approaches.

As of September 12, 2001, there were 3.98 billion nucleotides of non-redundant DNA sequence in GenBank, much of which codes for proteins. These sequences come from many organisms that have diverged from each other to varying extents. Alignments among related protein sequences has become a major tool for inference of protein structure, function, and evolution. We will cover the major methods for generating sequence alignments, practical use of web-based tools for identifying and analyzing sequences, the relationships between 3-dimensional protein structure and sequence divergence, and the meaning and interpretation of evolutionary trees in defining protein families and super-families.

Classical genetic analysis is a powerful approach to dissect complex biological processes. Selective removal or alteration of specific proteins allows inferences about processes too complex to study effectively with biochemical or molecular approaches and can provide definitive functional assignments. We will employ genetic analysis to identify and order genes in a pathway, determine the tissue and temporal requirement for gene function, and distinguish among competing hypotheses to explain biological phenomena. As an example, we will discuss the yeast pheromone response, infering gene function by examining perturbations in STERILE mutants that lack the ability to mate. Methods include complementation tests, single and double mutant phenotype analyses to construct a functional pathway, use of activating mutations, suppressor screens, and gene disruptions.

Students with strong genetic backgrounds should register for GEN551 and obtain additional information from Jim Thomas (jht@genetics.washington.edu) or Celeste Berg (berg@genetics.washington.edu). Students with more diverse educational backgrounds, i.e., computer science, physics, chemistry or engineering, should register for MBT510 and obtain additional information from Debbie Nickerson (debnick@u.washington.edu).