W.-L. Kuo, C. Collins, J. Cochran, K. Greulich, D. Kowbel, J. Marstaller, K. Myambo, D. Pinkel, L. Riedell, Yu-Ping Shi, M. Wang, H.-U. Weier, P. Yue, M. Zorn, and J. Gray.
LBL/UCSF Resource for Molecular Cytogenetics, Dept. Laboratory Medicine, University of California, San Francisco, CA 94143-0808 and Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
The LBL/UCSF Resource for Molecular Cytogenetics has been created to develop probes and associated technologies to facilitate the cytogenetic analyses. One goal of this Resource is to develop reference probes at ~5 Mb intervals spanning the human genome. These probes are mapped using fluorescence in situ hybridization (FISH), contain important genes or genetically mapped sequence tagged sites (STSs) to integrate genetic and physical maps and are sufficiently large to perform well as FISH probes in clinical material.
Human genomic libraries cloned into P1, PAC and BAC vectors are the major sources of these probes because clones from these libraries have insert sizes ranging from 75-300 kb making them well suited as molecular cytogenetic probes. Moreover, a very low frequency of chimerism and cross hybridization, less than 1 %, has been observed upon mapping these clones.
To date, approximately one thousand probes have been developed or acquired by the Resource. These include probes selected for 579 specific genes or genetically mapped loci, 17 chromosome-specific centromeric probes, 31 whole chromosome paints and 202 anonymous probes. Molecular cytogenetic probes have been developed for genes known to be important. These include E-cadherin, RARA, p53, PML, HBE, TCRA, SRC, GADD45, BTK1, c-myc, sis, gli, NFKB2, NTRK1, Bcl-x, E2F-1, ERBB2, VHL, MTS-1 and genes at 20q13.2. Clones have also been selected that localize to genetic intervals implicated in Cri-du-Chat, Angelman/Prader-Willi, Langer-Giedion, Miller-Dicker, and Di George syndromes. We expect to complete development of probes to genes or genetically mapped loci spaced at ~ 5 Mb intervals of the human genome by next year.
Mouse chromosome-specific P1 clones have been developed to facilitate chromosome identification. To date, we have mapped 44 probes covering 34 loci. These probes were selected in collaboration with Dr. Eric Lander at the Whitehead Institute and Genome System to genetically mapped loci proximal to the chromosome centromere and at the telomere of each chromosome.
Information about probes developed by the Resource and their availability can now be surveyed on the Internet Web server at URL http://rmc-www.lbl.gov/.
*Supported by a grant from the Director, Office of Energy Research, Office of Health and Environmental Research, Department of Energy, under contract DE-AC-03-76SF00098 and Vysis, Inc.
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