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| Author: Aaron Hall |
Emilio Garcia summarized the state of the LLNL high-resolution chromosome 19 physical map and discussed its value for gene hunting and detailed analyses of genome organization.
Physical Map
The cosmid-based physical map now consists of 32 islands, 3 in the q arm and 29 in the p arm, with average gap sizes of 90 and 70 kb, respectively. A unique map feature is its metric backbone, in which distance between ordered contigs was estimated using FISH; gap distances are known. The contigs are being converted to an EcoR I map (now covering 42 Mb, or 83% of the chromosome) that provides the minimum tiling path for reducing redundant sequencing.
Now spanning 90% of chromosome 19 euchromatin, the comprehensive map has been enriched with the addition of over 170 genes, 176 cDNAs, 315 STSs, 135 polymorphic markers, over 400 YACs, and 45 Mb of EcoR I restriction mapping.
Applications
In a collaborative project with researchers in France and South Africa, LLNL supplied cosmid clones every 200 kb across a chromosomal region identified in population studies as associated with a cardiac conduction disease (progressive familial heart block). These cosmids will enable researchers to search for polymorphic markers across the region. The LLNL map also provides some potential candidate genes to be tested.
Garcia pointed out that the map can serve as a bridge from cytogenetic knowledge to molecular analysis. For example, researchers have been analyzing a translocation (chromosomal exchange) between chromosomes 6 and 19 that is associated with a hereditary renal dysplasia. Searching large numbers of cosmid clones across a chromosomal region led to a particular translocation being localized fairly quickly to a specific cosmid. The translocation region in the cosmid was sequenced and found to have high homology to the USF2 (upstream stimulatory factor 2) gene. USF2 is a ubiquitously expressed factor implicated in the expression of several tissue-specific or developmentally regulated genes. |
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