RELATIONSHIP BETWEEN PROTEIN COMPLOTYPES AND DNA VARIANT HAPLOTYPES -COMPLOTYPE-RFLP CONSTELLATIONS (CRC)

From the study of 52 families and 15 homozygous typing cells, 234 MHC complement haplotypes were characterized for features in the DNA of th e complotype region: C2/Sst I (2.75, 2.70, 2.65, and 2.40 kb), BF/Taq I (6.6 and 4.5 kb), C4 5'/Bgl II (15 and 4.5 kb), C4 5'/Taq I (7.0, 6. 4, 6.0 and 5.4 kb) and C4 3'/Xba I/BamH I (11 and 4+7 kb) restriction fragment length polymorphisms (RFLP's), by the presence or absence of C4A, C4B, CYP21A and CYP21B genes and by duplications. Nineteen (of ov er 1000 theoretically possible) complotype-RFLP constellations (CRC's) were found. The 9 CRC's with two C4 and CYP21 genes were designated A through I. CRC's Bdup and Ddup were like B and D but had duplicated C 4B-CYP21B genes. The remaining CRC's had deletions of C4 and/or CYP21 genes and were designated Bdel, Cdel and the like. Individual compleme nt alleles and complotypes were not randomly distributed among the CRC 's. Some complotypes, such as SCO1, SC02 and F1C30, were restricted to only 1 CRC; others, such as SC31, FC31, and SC30, were found in sever al CRC's. Some of the CRC's contained a single complotype, others cont ained several. Remarkably, there are about 30 CRC-specified complotype s with frequencies of .01 or higher and 14 of .02 or higher. A number of evolutionary origins of complement alleles and complotypes are sugg ested by the relationships among CRC's. Approximate normal frequencies of the undeleted CRC's were A = .27, B = .19, Bdup = .02, C = .17, D = .07, Ddup = .02, E = .06, F = .05, and G = .02. Thus, CRC's without deletions accounted for 88% of normal complotyyes. Since the frequency of Bdel, with a deletion of C4A, was .12, 10 CRC's accounted for all observed normal caucasian MHC haplotypes. (C) American Society for His tocompatibility and Immunogenetics, 1997. Published by Elsevier Scienc e Inc.