ABSTRACT P.I. Anna Di Rienzo SBR- 9317266 Simple sequence repeats (SSR's or microsatellites) are a group of repetitive DNA sequences that show very high levels of variation in length. They are found in a broad range of eukaryotes, particularly mammals. They they have become particularly important in human genetics because 1) the instability of some SSRs is the root cause of some diseases, including some forms of cancer, fragile X mental retardation syndrome, and Huntington's disease, 2) they have become the tool of choice to construct linkage maps of the entire genome, and 3) the appear to be a very powerful tool for studies of genomic diversity in humans, and for reconstructing human population histories. This study, by an extremely well-trained younger scientist, will survey SSRs and their variability extensively in carefully chosen human populations. She and her group will analyze at least 100 SSRs in order to characterize how the mutation process occurs - if in single steps, or multiple steps. They will estimate the proportion of multi-step and single-step mutation events for each locus. In addition, they will reconstruct the population histories of the six populations to be examined by sequencing the most variable region of mtDNA in the same samples, so that this can be compared with the pattern of differences in SSRs. This reconstruction will determine the most realistic population scenarios for simulation of the mutation process models, and will allow the dissection of the mutational events leading to the observed population variation. *** Panthrojfried9317266.abs ` b ! ! ! D d d ( Times New Roman Symbol & Arial ` ` ` > " h T % T % T = Jonathan Friedlaender Jonathan Friedlaender
