#36
DETERMINATION OF HLA HAPLOTYPES IN THE INTERPRETATION OF HLA TYPING.
Pedro Cano M.D. 1 and Marcelo Fernandez-Vina Ph.D. 1. 1 Laboratory Medicine, M.D. Anderson Cancer Center, Houston, TX, USA .
HLA typing should not be interpreted as the independent allele assignment in different genetic loci. Linkage disequilibrium is strong enough to consider HLA-B-C as one block and HLA-DRB1-DRB3/4/5-DQB1 as another block. Allele assignment for these blocks should be carried out as a single step. A weaker linkage disequilibrium exists between the other loci and these blocks. Knowledge of the extent and nature of these associations between genes and gene blocks is essential in the interpretation of HLA typing results. The meaning of an HLA phenotype is conveyed by the inference of two haplotypes from the phenotype and the description of these haplotypes in terms of their position in the distribution of all haplotypes in a given reference population. The distinction must be made between 
haplotypes in full linkage disequilibrium and haplotypes resulting from random recombination. Only if a rare allele is encountered in a haplotype in full linkage disequilibrium there is hope of finding a match. Many described alleles have not been documented sufficiently to be considered in the interpretation of genetic typing reaction patterns. Their inclusion can also lead to unfortunate decisions in the design of typing reagents. Contrary to what might be believed, the polymorphic universe of HLA genes is rather limited. After typing more than 22,000 samples, 203 B-C blocks, 151 DRB1-DRB3/4/5-DQB1 blocks; and 56 A, 111 B, 36 Cw, 59 DRB1, 22 DRB3/4/5, 22 DQB1, and 20 DPB1 alleles were identified. Knowledge of the boundaries of the HLA polymorphic universe is essential in the interpretation of HLA typing. Haplotype frequencies, rather than allele frequencies, are also the key to determine reliable genetic distances between populations.