As a consequence of the collaborative efforts of several large international groups, including the Cooperative Human Linkage Center (CHLC), the goal of obtaining a 2 - 5 centiMorgan (cM) human genetic map has been obtained. The realization of this goal, however, does not signify that the human genetic map is complete. To the contrary, this map represents only an important step in the generation of a collection of genetic reagents that will facilitate the larger goals of the Human Genome Project. The FY93-FY98 strategic goals of the Human Genome Project recognized that to achieve the larger goals of the program investment in areas in addition to sequencing was required. These goals restated that improvement of genetic mapping technology continues to be important. Key areas described as important included the development of: ) genotyping methods that are amenable to automated analysis and are much more cost- effective and easier to use than currently available resources, 2) new types of genetic markers, and 3) new analytical tools that will maximize the utility of the genetic map, especially for application to the dissection of complex traits. It is the overall goal of this proposal to facilitate the continued development and use of the human genetic map. Within this proposal the objectives of the previous application will be continued and expanded. Effort will be made to continually update the genetic map with genotype data from the CEPH reference panel as well as with genotype data generated on alternative family resources. Genetic map data will be integrated with physical mapping data to obtain """"""""proxy"""""""" locus positions for polymorphic markers. Current efforts to extend analytic methods for using genetic maps to identify genetic components of complex traits will also be continued. Simulation studies will be performed to assess optimal marker characteristics and spacing for complex trait analysis. Analytic tools that integrate non-parametric linkage and disequilibrium analysis will be explored. New efforts will focus on development of analytic tools that will facilitate the identification of sequence variation which will have the potential of utility as new genetic markers. These methods will identify """"""""candidate"""""""" polymorphisms from publicly available sequence data. Develop algorithms to identify STR and bi-allelic polymorphisms from cDNA-UTRs, ESTs, and genomic DNA sequence.
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