2. MHC diversity arises from: Polygenicity Polymorphism Co-dominance Linkage disequilibrium

3. Polygenicity: Polymorphism: 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 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

4. 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

5. 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.)

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

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

8. Genetic organization in the mouse is similar… continue to think about polygenicity, polymorphism, co-dominance, and linkage disequilibrium

9. And, the result is:

10. So… that’s the genetics… what does the synthesis of the protein look like?

11. “Classical” and “non-classical” MHC’s “Classical” are expressed continuously. “Non-classical” are expressed in specific tissues and/or at specific times.

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

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