Systemic lupus erythematosus has a complex and incompletely understood pathogenesis, important components of which appear to be dependent upon the genetic constitution of the patient. The lambda(S) measure of genetic potential for lupus to be accessible to modern genetic approaches may be as much as 30 in European-Americans, suggesting that there is ample opportunity to find the genes that cause lupus with existing technologies. We are now genotyping 93 pedigrees at 308 loci and are preparing to genotype another 71 pedigrees (total of 1009 subjects). Power to find linkage is directly related to the size of the collection of pedigrees. The first major aim of this project of the SCOR will be to integrate the genetic studies of lupus underway in Minneapolis (where ABI markers are being used) and Oklahoma City (where Weber set #8 markers are being used). We proposed to genotype the 1009 subjects from 164 pedigrees in the Oklahoma collection with those ABI markers from region's with possible genetic effects (estimated to be over 20). We will help evaluate a number of candidate genes by other members of the SCOR, particularly project #3. In addition, we plan to contribute further toward the goal of identifying the genes involved by developing a resource of simplex pedigrees suited for analysis by transmission and disequilibrium. This collection will also be integrated with the collections being assembled by other members of the SCOR. This work is likely to help identify the genetic origins of lupus and provide a new foundation from which to understand and treat this enigmatic disorder.
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