THE LOCATION OF A DISEASE-ASSOCIATED POLYMORPHISM AND GENOMIC STRUCTURE OF THE HUMAN 52-KDA RO SSA LOCUS (SSA1)/

Sera from approximately 30% of patients with systemic lupus erythemato sus (SLE) contain high titers of autoantibodies that bind to the 52-kD a Ro/SSA protein. We previously detected polymorphisms in the 52-kDa R o/SSA gene (SSA1) with restriction enzymes, one of which is strongly a ssociated with the presence of SLE (P < 0.0005) in African Americans. A higher disease frequency and more severe forms of the disease are co mmonly noted among these female patients. To determine the location an d nature of this polymorphism, we obtained two clones that span 8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six exons were identified, and their nucleotide sequences plus adjacen t noncoding regions were determined. No differences were found between these exons and the coding region of one of the reported cDNAs. The d isease-associated polymorphic site suggested by a restriction enzyme m ap and confirmed by DNA amplification and nucleotide sequencing was pr esent upstream of exon 1. This polymorphism may be a genetic marker fo r a disease-related variation in the coding region for the protein or in the upstream regulatory region of this gene. Although this RFLP is present in Japanese, it is not associated with lupus in this race. (C) 1994 Academic Press, Inc.