High-resolution transcript map of the region spanning D12S1629 and D12S312at chromosome 12q13: Triple A syndrome-linked region

For those searching For human disease-causing genes, information on the pos ition of genes with respect to genetic markers is essential. The physical m ap composed of ESTs and genetic markers provides the positional information of these markers as well as the starting point of gene identification in t he form of genomic clones containing exons. To Facilitate the effort of ide ntification of genes in the region spanning D12S1629 and D12S312, we constr ucted a high-resolution transcript map with PAC/BAC/cosmid clones. The stra tegy for the construction of such a map involved utilization of STSs for th e screening of the large insert bacterial chromosome libraries and a chromo some 12-specific cosmid library by hybridization. The contig was constructe d based on the STS contents of the clones. The resulting high-resolution tr anscript map of the region between P273P14/SP6 and D12S312 spans 4.4 cM fro m 66.8 to 71.2 cM of the Genethon genetic map and represents similar to2.4 Mb. It was composed of 81 BAG, 45 PAC, and 91 cosmid clones with a minimal tiling path consisting of 16 BAC and 4 PAC clones. These clones are being u sed to sequence this part of chromosome 12. We determined the order of 135 STSs including 74 genes and ESTs in the map. Among these, 115 STSs were una mbiguously ordered, resulting in one ordered marker per 21 kb. The order of keratin type Il locus genes was determined. This map would greatly enhance the positional cloning effort of the responsible genes for those diseases that are linked to this region, including male germ cell tumor as well as p almoplantar keratoderma, Bothnian-type, and triple A syndrome. This transcr ipt map was localized at human chromosome 12q13.