An approach to identify new genes in autoimmune diseases: lessons from rheumatoid arthritis.

: We have searched the human genome for genes that predispose to rheumatoid arthritis using fluorescence-based microsatellite marker analysis and affected sib-pair linkage studies. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DX1232, have been assigned, which we call RA1, RA2 and RA3 for rheumatoid arthritis disease loci. We are now assigning the death receptor 3 as a candidate gene for RA1, and the truncated form of Dbl proto-oncogene, which does not contain the 23rd and 24th exons, as disease gene for RA3. Microsatellite marker analyses seem to be promising and new genes are now being identified by reference to sequence tag sites.