POLYMORPHISM OF TAP GENES IN GRAVES' DISEASE

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The overall objectives are to detect genetic polymorphisms at the DNA level in African-American unrelated volunteer controls, in patients with Graves' Disease and their family members: to expand scientific knowledge regarding Graves' disease and the distribution of genes within the major histocompatibility complex in this ethnic group; and to motivate minority graduate and undergraduate students to pursue biomedical research careers. The specific aims are to determine polymorphism in TAP1 and TAP2 genes within African-American volunteer controls and within Graves' disease patients; to sequence alleles of TAP1 and TAP2 associated with Graves' disease patients; to train students in basic and sophisticated molecular genetic techniques by using hands-on laboratory equipment, by participating in workshops and seminars, and by presenting research results at scientific local and national meetings. The hypothesis is that genetic polymorphisms that are unique to this ethnic group are present in the TAP region genes. HLA associations with Graves' disease have been reported for both Class I and Class II antigens. This study will add to the pool of knowledge on whether it is Class 1 and define the boundaries of the region within the major histocompatibility complex that determines susceptibility to Graves' Disease. There are new alleles to be detected. Transporters associated with antigen processing (TAP) genes are polymorphic and function to transport antigenic peptides to be loaded in HLA class I molecules. TAP1 and TAP2 are involved in restricted antigen processing. Class I antigens may be important in the development of class II associated disease. methods to be used are basic and sophisticated molecular genetic techniques of molecular biology; i.e., PCR based single strand conformational polymorphism (SSCP) method. PCR products will be subjected to SSCP analysis to correlate SSCP patterns with allelic sequence variation. Serological test will be done to determine if there are antibodies to microsomal antigen and to thyroglobulin. Much information will be obtained to greatly add to the pool of knowledge about TAP polymorphism, specifically in African-American volunteer controls and in patients with Graves' disease