The human sex chromosomes are thought to have evolved from a common ancestral homologous chromosome pair, and, therefore, share many regions of homology. The long- term objectives of Dr. Yen's research are to study the sequence organization of the human X and Y chromosomes, to compare regions of homology, and to isolate genes and elucidate their function. Her previous studies have focused on the homologous regions of Xp22.3 and Yq11.2. She has constructed physical maps of these regions, isolated and characterized genes, and studied aberrant chromosomes with disruptions in these regions in patients with clinical manifestation. For the next grant period, Dr. Yen will continue her efforts on the cloning and mapping of the human sex chromosomes. However, her studies will be directed to deletion interval 6 of the Y chromosome. This region is clinically important because genes in this region have been implicated in spermatogenesis. Many infertile males with microdeletions in this interval have been identified. A long-range restriction map of this region will be constructed, and the existing YAC contig will be converted into cosmid contigs. A binning strategy will be employed to facilitate the construction of the cosmid contigs. In addition, YAC deletion panels will be generated to assist the mapping of complex repetitive sequences, which are abundant in this region. New genes will be isolated and characterized, and their expression patterns and evolutionary conservation will be studied. Low copy Y-specific repetitive sequences in this region will be isolated and characterized, and their copy numbers and locations will be determined. Finally, deletion breakpoints of microdeletions in infertile males will be mapped and isolated, and the presence of repetitive sequences will be investigated. The results will provide a detailed physical map of this region, and may also give explanations of the causes of the high deletion frequency observed. In addition, characterization of genes isolated from this region will potentially add to the understanding of the process of spermatogenesis, and improve the management of the clinical problem of male infertility.
Showing the most recent 10 out of 22 publications
