This 3-year project focuses on the mouse and chimpanzee Y chromosomes and the chicken Z and W chromosomes, in the context of NHGRI's goals to sequence the genomes of these animals. We propose to (1) complete the mapping/sequencing of the mouse and chimpanzee Y chromosomes (each currently 50% sequenced) (2) complete the mapping/sequencing of the chicken Z chromosome (currently 30% sequenced) and (3) map/sequence 50% of the chicken W (currently 1% sequenced) as part of a 6-year goal to complete this chromosome. During the last 15 years, genomic studies have revealed that the human Y chromosome is biologically richer and medically more important than anyone would have predicted. These genomic studies recently culminated in a finished and annotated sequence of the human Y chromosome. To date, the human Y is the only sex-specific chromosome to have been sequenced from any species, vertebrate or invertebrate, plant or animal. Knowledge of its sequence allowed researchers to identify and characterize recurrent Y deletions, which have emerged as the most common of the known causes of infertility in men. We expect that the sex-specific chromosomes of three of NGHRI's high-priority sequencing targets - mouse (XX female/XY male), chimpanzee (XX/YY), and chicken (ZWfemale/ZZ male) - will also prove to beof great biomedical interest. The mouse and chimpanzee Ys will represent only the second and third Y chromosomes to be sequenced. We anticipate that the sequences of these Y chromosomes will offer new insight into the human Y's roles in health and disease and will provide essential infrastructure for elucidating mammalian and human germ cell development and spermatogenesis. The chicken Z and W chromosomes will be the first sequenced sex chromosomes from a species in which females, not males, bear the sex- specific chromosome. We anticipate that the sequences of the Z and W will inform our understanding of human biology by offering insights into vertebrate germ cell development, oogenesis, and sex determination.