BCM HUMAN GENOME PROGRAM CENTER

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The X chromosome of man comprises approximately 5% of the genome or 150 Mb. As of HGM 10, there were 44 cloned genes, 175 mapped genes and disease loci, and 212 polymorphic DNA markers (the largest number of any human chromosome). Intense investigation of the X chromosome relates primarily to the high frequency of genetic diseases manifested by hemizygous males and its role in sex development. Additional features which make the X chromosome a high priority for genome analysis include: 1) its high degree of homology across mammalian species (Ohno's law), 2) its regulated inactivation and reactivation in mammalian females (Lyon hypothesis), 3) its partial homology with the Y chromosome and the unique features of recombination between distal Xp and Yp, and 4) the presence of the HPRT gene, which makes the X chromosome amenable to a variety of somatic cell genetic strategies for mapping using forward or back selection at this locus. Choice of the x chromosome for complete mapping and sequencing is logical one for a molecular genetics program based in a medical school (Baylor College of Medicine) where significant strengths exist in medical genetics and molecular genetic basis of human disease. The college has made a strong commitment to the proposed Human Genome Program Center by dedicating over 5000 sq. ft. of additional space to its cores and research projects. To complement the existing nucleus of human molecular genetics research activity, we are adding to our Center basic research expertise in yeast genetics for vector development, mouse mapping for comparative studies, and a substantial computational expertise from Baylor and Rice University to address problems of data assembly and analysis. The two primary goals of the Center for the first five years of funding are: 1) Development of a YAC vector contig map of the entire X-chromosome within 2- 5 years and 2) development of sequencing technology capable of up to 5 megabases of contig sequencing annually.