Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families

Systemic lupus erythematosus (SLE) is the prototype of human autoimmune dis eases. Its genetic component has been suggested by familial aggregation (la mbda s=20) and twin studies. We have screened the human genome to localize genetic intervals that may contain lupus susceptibility loci in a sample of 188 lupus patients belonging to 80 lupus families with two or more affecte d relatives per family using the ABI Prism linkage mapping set which includ es; 350 polymorphic markers with an average spacing of 12 cM, Non-parametri c multipoint linkage analysis suggests evidence for predisposing loci on ch romosomes I and 18. However, no single locus with overwhelming evidence for linkage was found, suggesting that there are no 'major' susceptibility gen es segregating in families with SLE, and that the genetic etiology is more likely to result from the action of several genes of moderate effect. Furth ermore, the support for a gene in the 1q44 region as well as in the 1p36 re gion is clearly found only in the Mexican American families with SLE but no t in families of Caucasian ethnicity, suggesting that consideration of each ethnic group separately is crucial.