The parent project for this FIRCA application is an R01 grant to determine whether five candidate human chromosomal regions confer major susceptibility to SLE. The candidate regions were identified by mouse homologues, and will be studied by linkage and association methods in 300 multiplex families ascertained through UCLA clinics, which was intended to be an ethnically heterogeneous mix, since one of the hypotheses is that SLE-predisposing genes will be conserved across ethnic groups. This group has reported evidence for linkage of SLE to markers on chromosome 1q41-q42, and nonparametric allele sharing methods among affected sib pairs seemed to suggest that the greatest proportion of allele sharing occurred in the Asian subset, which included 10 sib pairs of southern Han Chinese descent. Wishing to extend upon this finding in an ethnically homogeneous subset, Dr. Tsao proposes a collaboration with investigators in the Department of Rheumatology at Ren Ji Hospital in Shanghai, China. The goals of the FIRCA grant are to identify and enroll 100 Chinese SLE-affected sibpair families, to genotype blood samples or buccal swabs with markers densely located in the candidate region, and to analyze the data using nonparametric linkage and association methods.
