MHC diversity arises from Polygenicity Polymorphism Codominance Linkage

Polygenicity: n [ISV] (1941) : possessing any of a group of nonallelic genes that

Co-dominance: • Full expression in the heterozygous state Linkage disequilibrium: • When the observed

MHC haplotypes are in disequilibrium: Two explanations are offered: 1. There has not been

Haplotype: • Think “Polygenicity, ” “polymorphism, ” “co-dominance, ” and “linkage disequilibrium”….

Genetic organization in the mouse is similar… continue to think about polygenicity, polymorphism, co-dominance,

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

Linkage disequilibrium Some haplotypes correlate with increased incidence of disease. Such association is measured

MHC- III • • • Complement Tumor necrosis factor Heat shock proteins Hydroxylases (generally)

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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”….

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 Some haplotypes correlate with increased incidence of disease. Such association is measured by a “relative risk” factor (RR). (again) RR = (Ag+/Ag-) disease ___________ (Ag+/Ag-) control Question: to what does “Ag+” refer? )

MHC- III • • • Complement Tumor necrosis factor Heat shock proteins Hydroxylases (generally) genes related to inflammation