MHC/HLA: Polymorphisms and population diversity

1
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

2
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

3
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)

4
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?)