The purpose of this project is to develop methodology for analyzing molecular population genetics data. Work this year has progressed in two areas: (1) Work has continued on estimating the recombination fraction between a marker and a disease gene from disease/marker association data. The effects on estimates of the recombination fraction of mutation at either the marker or disease locus were investigated. Results indicate that mutation is not an important force for typical mutation rates, unless the recombination fraction between the marker and disease locus is very small, or the disease allele is very rare in the general population. A model was developed to estimate the recombination fraction between a marker and disease gene using marker data from an admixed population such as the African American population. Preliminary results suggest that with this approach it is feasible to localize a disease gene. (2) Work is ongoing studying the behavior of variation at neutral loci linked to loci at which deleterious variation is maintained by a mutation-selection balance. An analytic expression for the expected nucleotide diversity was obtained in a region with deleterious mutation and recombination. With currently available estimates of the deleterious mutation rate and of selection coefficients, the results successfully predicted levels of variation for the entire third chromosome of Drosophila melanogaster except near the tips. To fit the low observed levels of variation at the tips required much smaller selection coefficients.
