Polymorphism in the HLA-I (HLA-A, B, and C) and HLA-II (HLA-DRB1, DQB1, DQA1, DPB1, and DPA1) loci is a hallmark of genetic risk for autoimmune diseases; for example, genetic variation in the HLA-II loci explains up to 30% of the genetic heritability in rheumatoid arthritis and type 1 diabetes4–8. The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.