OVERLAPPING GENOMIC SEQUENCES - A TREASURE TROVE OF SINGLE-NUCLEOTIDEPOLYMORPHISMS

dAn efficient strategy to develop a dense set of single-nucleotide pol ymorphism [SNP] markers is to take advantage of the human genome seque ncing effort currently under way. Our approach is based oil the fact t hat bacterial artificial chromosomes (BACs) and PI-based artificial ch romosomes (PACs) used ill long-range sequencing projects come from dip loid libraries. If the overlapping clones sequenced are from different lineages, one is comparing the sequences from 2 homologous chromosome s in the overlapping region. We have analyzed in detail every SNP iden tified while sequencing three sets of overlapping clones found on chro mosome 5p15.2, 7q21-7q22, and 13q12-13q13. In the 200.6 kb of DNA sequ ence analyzed in these overlaps, 153 SNPs were identified. Computer an alysis for repetitive elements and suitability for STS development yie lded 44 STSs containing 68 SNPs for further study. All 68 SNPs were co nfirmed to be present in at least one of the three (Caucasian, African -American, Hispanic) populations studied. Furthermore, 42 of the SNPs tested (62%) were informative in at least one population, 32 (47%) wer e informative in two or more populations, and 23 (34%) were informativ e in all three populations. These results clearly indicate that develo ping SNP markers from overlapping genomic sequence is highly efficient and cost effective, requiring only the two simple steps of developing STSs around the known SNPs and characterizing them in the appropriate populations.