Comparative genomics is a powerful tool for uncovering patterns of mutations within genes targeted in human health concerns. To examine structure and function, we sequence targeted genes across multiple species to identify the pattern and rate of substitutions. This report summarizes our completion of projects, current ongoing research, and initiation of new advances with bioinformatic tools used to investigate gene function in reproduction.[unreadable] We use genetic analysis of the cat family to model evolution, structure and function of genes linked with human health. At the Laboratory of Genomic Diversity (LGD), we have shown that the cat is a very useful model for human genetics based on results from Dr. Menotti-Raymond's group in the development of a cat genome map. [unreadable] [unreadable] In 2004-2005, we have completed projects on patterns of genetic change in Y-chromosome genes. We published a large study (3604 bp) of sequence from four Y-linked genes sequenced from 36 species of cat. We have completed another manuscript focused on the critical male-determining gene sex determining region Y gene (SRY) essential to male fertility in both human and cat. This manuscript is currently submitted and in review. [unreadable] [unreadable] Our ongoing projects include investigating the theory that genes on the X and Y chromosome evolve in very different ways from those on autosomes. Our data is based on nearly 24 kb from 37 species of cat. We are comparing rates of genetic change between protein-coding and noncoding regions between the X-chromosome, Y-chromosome and autosomes. This will give us a broad depiction of genome evolution that can assist in the study of human disease.[unreadable] [unreadable] In a new initiative, we are using newly published whole genome sequence of dog and cat with advanced bioinformatic tools to determine gene content and order of the cat Y chromosome. The project is focused on the development and implementation of multiple bioinformatic methods to efficiently identify genes, map their position on the cat Y chromosome, and investigate their function. By comparing cat with dog, mouse and human, new insights onto the evolution, structure and function of genes in the Y chromosome are possible. In particular, genes within the non-recombining region (which encompasses the majority of the euchromatin on the Y) are of key interest and are thought to have vital male-specific functions. Using the latest information generated by the whole genome sequence of the cat, we used bioinformatic tools to compare these traces with humans to identify, sequence and analyze patterns of genetic change in candidate genes thought to cause male infertility. This approach has proven fast and efficient and will continue to be developed through collaborations with colleagues at NCI-Frederick. [unreadable]