This 5-year project focuses on the mouse and chimpanzee Y chromosomes in the context of the NHGRI's goals to sequence the genomes of both animals. During the last decade, genomic studies have revealed that the male-specific region of the Y chromosome (the """"""""MSY"""""""") in humans is richer in genes and more important biologically and medically than most investigators would have predicted. These genomics studies recently culminated in a finished and annotated sequence of the human MSY. This sequence allowed researchers to identify and characterize recurrent MSY deletions, which have emerged as the most common of the known causes of infertility in men. It is likely that the Y chromosomes of two of NHGRI's high-priority sequencing targets -mouse and chimpanzee - will also prove to be of great biomedical interest and importance. However, as was the case with the human MSY, special efforts (beyond what is needed for most of the genome) will be required if the mouse and chimpanzee MSYs are to be sequenced. This is because of difficulties posed by 1) lengthy, near-perfect """"""""ampliconic"""""""" repeats on which many MSY genes are located in mammals, and 2) the present absence of maps, shot-gun sequence, or other infrastructure for study of the mouse MSY. Here it is proposed that the mouse and chimpanzee MSYs be sequenced using an approach that couples mapping and sequencing in a single analytical process that is amenable to iterative refinement. (This """"""""iterative mapping and sequencing"""""""" strategy was developed in the course of sequencing the human MSY.) Further, it is proposed that the genes of the mouse and chimpanzee MSYs be identified, and that similarities and differences among the human, mouse, and chimpanzee MSYs be analyzed and interpreted. These interspecies comparisons will provide a foundation for exploring the roles of the human Y chromosome in health and disease.
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