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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?)