Conservation Versus Polymorphism of the MHC in Relation to Transplantation, Immune Responses and Autoimmune Disease
The MHC comprises three megabases and includes both HLA and central polymorphic non HLA genes which are relevant to the immune response. Alleles at all MHC genes occur together in specific combinations or haplotypes inherited within families. The vast majority of these nuclear haplotypes are either conserved ancestral haplotypes (AHs) or recombinants between them. In our population approximately twenty such AHs occur with frequency of greater than 1% (some as frequent as 13%) and at least 70% of the population have at least 500 kilobases of one or more of these AHs. Many MHC alleles are specific for one AH whilst other alleles apparently shared between AHs can be split. It appears that within the MHC there are at least three conserved regions containing at least two or more contiguous loci which exhibit extensive polymorphism. Recombination between these regions can be identified but is rare within them. However, these frozen regions seem to be non randomly associated, perhaps through a cascade of protein peptide interaction.
KeywordsArthritis Recombination Electrophoresis Integrin Cytosine
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