DELETION ANALYSIS OF THE SHORT ARM OF CHROMOSOME 5

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A complete physical map of the short arm of chromosome 5 (5p) will be constructed. This region is amenable for study because one of the most common deletion syndromes, the cri du chat syndrome, is the result of a deletion in this region. Viable terminal deletions, interstitial deletions, and translocations have been identified in cri du chat patients which have been localized throughout the short arm. Through the isolation of 50 somatic cell hybrids containing these deleted chromosomes, it has been possible to localize several hundred DNA fragments from a chromosome 5 specific library to over 30 distinct regions of 5p. This volume of physical mapping data will speed the continued mapping of this chromosome arm through the use of cosmid and YAC cloning until large contig maps are generated and linked together. This will be accomplished through a combination of somatic cell genetics, pulsed-field gel electrophoresis, and cosmid and YAC walking. The construction of a physical map of 5p is of importance for the following reasons: 1) One of the most common segmental aneusomies, cri du chat syndrome, is associated with loss of chromosomal material in this region. Further localization of the critical region (5pl5.2) for this syndrome and identification of potential genes will be enhanced by this cloning effort. 2) A large chromosomal region (5pl4) has been identified which when deleted, does not result in any mental or developmental deficiencies. The genetic make-up of this region will be of interest. 3) The localization of over 60 chromosomal breakpoints within 5p makes this chromosomal region a rich resource for experiments focused on understanding more clearly the events that lead to chromosomal breakage and repair. Over 15 breakpoints have been localized to 5pl5.1 alone.