This application is in response to an RFA with the goal of creating a high density map of restriction fragment length polymorphisms (RFLPs) of .the human genome. We have recently localized the genes for Alport syndrome to Xp and Neurofibromatosis to the pericentric region of chromosome 17. As part of these studies, we have isolated and characterized probes from these chromosomes. In this application, we propose to continue isolating probes on X and 17 until there are 200 markers for the X and 100 for chromosome 17 yielding an initial map with an average distance between markers of approximately 1 centiMorgan. The maps will be based on linkage relationships determined in the CEPH reference families. We have established collaborations with four different laboratories which are isolating and/or characterizing a wide variety of physical breakpoints on chromosome 17. We will use a set of previously characterized X-chromosome rearrangements and novel X-chromosome- fragment containing hybrids available to us from Hunt Willard to physically localize X-linked polymorphic probes. We will apply a series of models which we have developed which integrate cytological, physical, and genetic data, which will estimate chiasma distributions and chiasma interference, improve the ordering of multiple loci, and account for sex differences in recombination. Gaps in the map which are found with these methods will be filled by finding new polymorphism for probes known to be in the appropriate region.
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