TITLE PAGE Comparative analyses of human single- and multi-locus tandem repeats

Using the compiled human genome sequence, we systematically catalogued all tandem repeats with periods between 20 and 2000 bp and defined two subsets whose consensus sequences were found at either single (slTRs) or multiple loci (mlTRs). Parameters compiled for these subsets provide insights into mechanisms underlying the creation and evolution of tandem repeats. Both subsets of tandem repeats are non-randomly distributed in the genome, being found at higher frequency at many but not all chromosome ends and internal clusters of mlTRs were also observed. Despite the integral role of recombination in the biology of tandem repeats, recombination hotspots co-localized only with shorter microsatellites and not the longer repeats examined here. An increased frequency of slTRs was observed near imprinted genes, consistent with a functional role, while both slTRs and mlTRs were found more frequently near genes implicated in triplet expansion diseases, suggesting a general instability of these regions. Using our collated parameters, we identified 2230 slTRs as candidates for highly informative molecular markers. Ames et al. Human tandemly-repeated sequences 4