Exceptional Chromosome Regions II



Chromosome 19: Sequencing Status and Remaining Problem Regions

Anne Olsen
DOE Joint Genome Institute, Walnut Creek, CA, 94598

The map of chromosome 19 consists of seven contigs spanning a total of over 57 Mb. It covers >98% of the length of the p and q arms, as estimated by pronuclear FISH and restriction mapping. The five remaining map gaps (excluding the centromere) are estimated by FISH to be small (i.e. less than single BAC size), but we have been unable to close them by hybridization screening of cosmid and BAC libraries, BAC end sequence analysis, or analysis of FPC contigs. The most distal p-arm gap occurs within the SLI gene and is spanned by cDNAs but no genomic clones. Two of the gaps are adjacent to, or within, areas with concentrations of problem repeats that have presented challenges for sequencing and probe development.

Map coverage appears to extend relatively close to the centromere and telomere on each arm. Sequence from the most proximal p-arm and q-arm clones contains alpha satellite repeats, suggesting that the map extends close to the centromeric junction. The most distal p-arm cosmid is highly homologous to a telomeric YAC, yRM2001, and cosmids from this region exhibit FISH signals on multiple telomeres. Sequence from the most distal q-arm cosmid contains small blocks of (TTAGGG)n repeats, suggesting a subtelomeric location. The most distal q-arm cosmids also have FISH signals on multiple telomeres.

A total of 39 Mb of unique sequence, about two-thirds of the chromosome, is now finished. Most of the remainder of the chromosome is currently in finishing, but about 2 Mb, distributed in 7 locations, has been unfinishable due to problem repeats. Cosmids are being sequenced to supplement BAC coverage to assist in finishing these areas, but special sequencing strategies may be required for some repetitive regions. A summary of the current status of the map and finished sequence, indicating the location of problem repeat regions, is illustrated in the accompanying figure (drawn to scale, except gap sizes exaggerated for visibility).


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