Transcript MHC 2

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
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Complement
Tumor necrosis factor
Heat shock proteins
Hydroxylases
(generally) genes related to inflammation