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| Author: Aaron Hall |
Research groups led by Beverly Emanuel at the Children's Hospital of Philadelphia (CHOP), the University of Pennsylvania, and the Fox Chase Cancer Center and by Tom Hudson and Eric Lander at Whitehead Institute-Massachusetts Institute of Technology published a detailed physical map of human chromosome 22 in the January 11 issue of Human Molecular Genetics. The map, which provides about 70% coverage of the chromosome in 15 YAC contigs, is the product of an ongoing collaboration between two genome science and technology centers (GESTECs) supported by the NIH National Center for Human Genome Research (NCHGR). Similar low-resolution comprehensive maps have been published for chromosomes Y and 21 (see HGN 4(4), 1-4 (November 1992).
Emanuel said, "Our map provides information of immediate use to anyone who is looking for genes and disease-causing rearrangements on this chromosome." The new map also provides a framework for constructing higher-resolution physical maps for eventual sequencing of the chromosome.
The 587 YAC clones were assembled into contigs by STS-content mapping and ordered along the chromosome using cytogenetic breakpoint, meiotic, and pulsed-field gel maps. Most YACs were identified from the CEPH-Genethon original and mega-YAC libraries (average insert sizes, 470 and 900 kb, respectively); additional YACs were isolated from the Washington University YAC library and from a chromosome 22-specific YAC library generated at the Philadelphia GESTEC from GM10888, a chromosome 22-only hybrid cell line.
Callum Bell (CHOP), the paper's lead author, pointed out that contig construction was complicated by deletions and permutations caused by chromosomal regions that are unstable when cloned into YACs. To overcome this problem, researchers assembled contigs using a computer algorithm developed by David Searls (University of Pennsylvania Medical School) to show a series of possible marker orders. This approach helped to minimize gaps in the map and reveal possible ambiguities in assigning marker order.
YAC contigs provide extensive coverage of the chromosome long arm, with the highest marker density in the 22q11.2-22q13.1 region. The distal end of the long arm appears to be resistant to YAC cloning; for this region, the group is exploring use of other cloning vehicles such as BACs, P1 phage clones, PACs, and cosmids. Other efforts to achieve complete coverage of the long arm include generating additional STSs for further screening of large genomic clones and the use of Alu-PCR hybridization methods.
The third-smallest human chromosome at about 50 million bp, chromosome 22 is thought to contain as many as 2000 genes and pseudogenes. More than 100 have been mapped, including genes for cancers such as Ewing's sarcoma, Burkitt's lymphoma, meningiomas, acoustic neuromas, and acute lymphoblastic leukemia. Recent reports suggest that the chromosome may contain a tumor-suppressor gene involved in breast cancer and schizophrenia. Also linked to chromosome 22 are Cat Eye syndrome, DiGeorge syndrome, isolated congenital heart defects, velocardiofacial syndrome, and neurofibromatosis 2. |
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