Joomyeong Kim[2], Mark Shannon, Linda Ashworth[1], Elbert Branscomb[1], and Lisa Stubbs
Biology Division, Oak Ridge National Laboratory, P.O. Box 2009, Oak Ridge, TN 37831-8080
Several lines of evidence now suggest that the human genome carries hundreds of zinc-finger (ZNF)-containing genes and that many of these genes are arranged in clusters. Curiously, a disproportionate number of these genes map to human chromosome 19, and detailed physical mapping performed at Lawrence Livermore National Laboratory's Human Genome Center has further demonstrated that ZNF genes are primarily located in six major clusters dispersed throughout the length of the chromosome. As part of an extensive man-mouse comparative mapping study of human chromosome 19 conducted by investigators at the Oak Ridge and Lawrence Livermore National Laboratories we have targeted for in-depth study a region spanning approximately 2.5Mb near the telomere of H19q and occupying most of subband 19q13.4. Since previous studies have indicated that genes bordering this region are conserved in proximal mouse chromosome 7 (Mmu7), we predicted that the large array of ZNF genes known to be present in 19q13.4 would be similarly conserved in the syntenically homologous region of Mmu7.
As a preliminary step for characterization of this region, we have assigned several known ZNF cDNA sequences to the 19q13.4 physical map. Two genes, ZNF134 and ZNF132, have been localized to centrally located contigs (577/1514 and 32, respectively) using probes under high stringency conditions. However, under low stringency conditions, these two probes detected overlapping sets of contigs, which include several neighboring 19q13.4 contigs, suggesting that the two genes are members of a large clustered family. Physical mapping of several ZNF-positive contigs from this central region suggests that each carries 5 or more related genes and that the entire region is likely to contain 50 or more. We have also used these gene probes to map related sequences in the mouse using the interspecific backcross system. As expected, each probe detected several loci, which mapped together in the related region of Mmu7. These data suggest that the mouse genome contains a ZNF134-related gene cluster in a region that is syntenically homologous to human chromosome 19q13.4. These largely unexplored regions provide a rich resource for studying the structure, function, and evolution of the many clustered gene families located throughout the human and mouse genomes.
This work was supported by USDOE under contract DE-AC05840R21400 with Lockheed-Martin Energy Systems, Inc., and contract W-7405-ENG-48 with the Lawrence Livermore National Laboratory.
[1] Human Genome Center, Lawrence Livermore National Laboratory
[2] Corresponding author