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Transcript
MHC diversity arises from: • Polygenicity • Polymorphism • Co-dominance • Linkage disequilibrium Polygenicity: n [ISV] (1941) : possessing any of a group of nonallelic genes that collectively control the inheritance of a quantitative character or modify the expression of a quantitative character Polymorphism: n [ISV] (1839) : the quality or state of being able to assume different forms: as a : existence of a species in several forms And by extension: existence of a gene in several forms Co-dominance: • Full expression in the heterozygous state Linkage disequilibrium: • When the observed frequencies of haplotypes in a population does not agree with haplotype frequencies predicted by multiplying together the frequency of individual genetic markers in each haplotype. http://hal.weihenstephan.de/genglos/asp/genreq.asp ?nr=519 MHC haplotypes are in disequilibrium: Two explanations are offered: 1. There has not been enough “evolutionary” time to achieve equilibrium 2. Some allelic sequences in the haplotype are adaptive (i.e., they are suited to displaying frequently occurring “foreign” peptides.) Haplotype: • Think “Polygenicity,” “polymorphism,” “co-dominance,” and “linkage disequilibrium”…. Haplotype: • Think “Polygenicity,” “polymorphism,” “co-dominance,” and “linkage disequilibrium”…. Genetic organization in the mouse is similar… continue to think about polygenicity, polymorphism, co-dominance, and linkage disequilibrium And, the result is: So… that’s the genetics… what does the synthesis of the protein look like? “Classical” and “non-classical” MHC’s “Classical” are expressed continuously. “Non-classical” are expressed in specific tissues and/or at specific times. Linkage disequilibrium (again) Some haplotypes correlate with increased incidence of disease. RR = Such association is measured by a “relative risk” factor (RR). Question: to what does “Ag+” refer?) (Ag+/Ag-) disease _____________________ (Ag+/Ag-) control MHC- III • • • • • Complement Tumor necrosis factor Heat shock proteins Hydroxylases (generally) genes related to inflammation
