Identification of the gene loci that predispose to rheumatoid arthritis

We have searched the human genome for genes that predispose to rheumatoid a rthritis (RA) using fluorescence-based microsatellite marker analysis and a ffected sib-pair linkage study, A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic m icrosatellite marker loci. Markers were amplified by the PCR using fluoresc ence-tagged primers and sized based on the difference of CA repeats on DNA, Linkage analysis was made using maximum lod score (MLS), The MLS for D1S21 4 and D8S556 was 3.27 and 3.33, while the MLS for the HLA-DRB1 region was < 3.0. According to detailed analysis by single-point analysis using MAPMAKER /SIBS, the MLS for D1S253 and D1S214 was 3.77 and 3.58. The MLS by multi-po int analysis was 6.13 for D1S253. The MLS for D8S556 by single-point analys is was 4.20. The MLS for DXS1232 was 2.35 by single-point analysis, whereas the MLS for the region 2 cM right to DXS1232 and the region between DXS122 7 and DXS1200 was 3.03 and 2.93 by multi-point analysis. Three principal ch romosome regions of linkage, D1S253/214, D8S556 and DXS1232, have been iden tified which we call RA1, RA2 and RA3 for RA disease loci.