We have developed a methodology for identification and fine mapping of chromosome-specific transcripts. Combining digestion of DNA with different restriction enzymes, ligation to 'bubble' linkers, and PCR amplification from Alu and 'bubble' primers, we have synthesized human chromosome 1- specific sequences from DNA of a somatic cell hybrid, A9Neo1. After hybridization to human fetal brain cDNA, we could efficiently capture chromosome 1-specific cDNAs. The cDNAs were sequenced and used as probes in hybridizations to high-density filters containing the arrayed CEPH Mega-YAC library and to the arrayed cDNA library from infant brain made by B. Soares, which has been extensively sequenced. By this approach we have been able to select chromosome 1-specific cDNAs, to map them to chromosome 1 YAC contigs, and to identify and map corresponding longer cDNAs and ESTs.
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