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Transcript
MHC/HLA: Polymorphisms and population diversity MHC - major histocompatibility complex (or HLA - human leukocyte antigens) are still a biological conundrum as to their function – originally known as the “transplantation antigens” These are highly polymorphic due to large number of alleles in population Haplotype genotype and phenotype Both haplotypes of gene are expressed - no allelic exclusion HLA typing allows one to follow HLAs in a pedigree, and then, by common sense analysis, to assign haplotypes (sets of adjacent linked genes) and to determine recombination High level of population polymorphism For example, the Class I antigens: – HLA-A - 57 alleles – HLA-B - 111 alleles – HLA-C - 34 alleles These genes are therefore good for linkage analysis! (highly likely to find heterozygosity and linkage-phase known individuals) MHC and disease Certain HLA antigens are associated with disease, primarily but not exclusively, autoimmune diseases Association can be due to linkage disequilibrium - e.g., hemochromatosis and HLA-A3 – why? unknown (HLA protein responsible for predisposition? or unidentified susceptibility genes in HL cluster?)
