The G allele of rs11086998 changes the amino acid sequence of CD40 at position 227 from proline to alanine and is enriched in persons from Mexico and South America. (A) Amino acid sequence of the CD40 intracellular domain. The position of proline 227 (red asterisk) and the location of the downstream TRAF binding sites (blue boxes) are noted. (B) SNP rs11086998 was genotyped in the Human Genome Diversity Panel (HGDP) representing 7 geographic regions worldwide. Samples typed were from people from equatorial Africa (n = 150), Central Asia (n = 67), the Middle East (n = 345), East Asia (n = 226), Melanesia (n = 39), Europe (n = 119), and Mexico and South America (n = 108). (C) Results from the Central and South American samples: Pima (n = 25), Mayan (n = 24), Colombian (n = 13), Karitiana Brazilian (n = 24), and Surui Brazilian (n = 21). (D) Thirteen markers across CD40 were genotyped in Central and South American (n = 108), European (n = 119), Central Asian (n = 43), and East Asian (n = 59) donors to the HGDP. The predicted ancestral haplotype is shown in blue, with haplotype-tagging SNPs shown in red; the P227A SNP is shown in yellow, with adjacent haplotype-tagging SNPs shown in purple. Haplotypes were analyzed by Haploview.⁵⁰