Complotypes and extended haplotypes in laboratory medicine.
The region on the short arm of the sixth human chromosome encoding class I and class II histocompatibility antigens involved in immune recognition also encodes a group of molecules unrelated to HLA termed class III which includes C2, C4, and factor B. The four genes encoding the complement proteins occupy about 120 kb of genomic DNA between HLA-B and HLA-DR and are closer to HLA-DR. The four genes are inherited as a single unit, without observed crossover, called a complotype, designated by its BF, C2, C4A, and C4B alleles. There are about fifteen complotypes with frequencies of 0.01 or higher on normal caucasian chromosomes. Analysis of linkage disequilibrium between HLA-B, HLA-DR alleles, and complotypes reveals that about 30% of normal caucasian chromosomes consist of fixed sets called extended or fixed haplotypes. There are over a dozen such extended haplotypes defined by their HLA-B, DR and complotype alleles. They appear to contribute most of the previously described linkage disequilibrium between HLA-A/HLA-B and HLA-B/HLA-DR allelic pairs as well as most of the known HLA marker-disease associations. It is postulated that extended haplotypes consist of fixed DNA over at least the 10(6) base pairs of the HLA-B-DR interval, and independent examples in apparently unrelated individuals are thus identical or nearly identical over this interval. A practical consequence of this concept is the possible prediction of successful tissue transplantation donor-recipient pairs.
Alper
C A
CA
Center for Blood Research, Dana-Farber Cancer Institute, Boston, Mass.
Awdeh
Z L
ZL
Yunis
E J
EJ
D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D019411:Clinical Laboratory Techniques; D003165:Complement System Proteins / Q000235:genetics*; D005796:Genes; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex
D003165:Complement System Proteins