Immunogenetics

IMMUNOGENETICS

Criteria for defining immune defense genes : an overriding difficulty defining immune genes is that vertebrate gene products appear to have multiple uses. Incidentally, it has been proposed that the small size of the human genome is a constraint imposed by an efficient adaptive immune system^ref !

sequence related to known defense gene : there are sequences realated to immune system genes that have no known role in defense, including many superfamily molecules^ref. Some mouse class I-related genes may have interesting non-immune functions^ref1,
ref2
expressed specifically in immune tissues : not all sequences have such convenient expression patterns
expression induced by immuno-modulators such as interferons : such a list contains many plausible candidates as well as some molecules with more general roles such as cell-cell interaction^ref
part of a pathway, such as signal transduction or transcription regulation, that results in expression of defense molecules, such as NFkB : these pathways often encompass molecules with wide applicability
interact directly with pathogens or their products : e.g. TLR, lectin superfamily
result in immunodeficiency when disrupted : about 80 human genes have been analyzed^ref and many more mouse loci.

Some features of defense genes that may reflext their defense role :

polygeny : many examples including MHC, Ig, KIR, FcR
polymorphism : MHC, KIR, NOD, TLR
clustering : 2 types of clusters :

duplicated genes in cis
genes from different gene families such as MHC

linkage disequilibrium : MHC, KIR, FcR

allele conversion
gene conversion

generation of repertoires : somatic rearrangement in the adaptive immune system (Ig/TcR). Stochastic gene expression (KIR)
rapid evolution : the best example is NK receptors, which are very different in arrangement in related species. Anyway examples of sets of genes that are not necessarily defense related but appear to be evolving rapidly are Morpheus, and the mouse urinary proteins (MUPs)
co-evolution : e.g. antigen-processing and -presenting genes in the MHC
association with disease : not always easy to confirm, even in mouse knockouts, because of functional duplication
networking : applies generally, but crucial for defense, in inflammation for example

African-American women are significantly more likely to carry allelic variants known to up-regulate proinflammatory cytokines; odds ratios increased with allele dose. Odds ratios for African Americans versus Whites in genotypes up-regulating proinflammatory IL-1 (IL1A-4845G/G, IL1A-889T/T, IL1B-3957C/C, and IL1B-511A/A) ranged from 2.1 to 4.9. The proinflammatory cytokine IL-6 IL6-174 G/G genotype is 36.5 times (95% confidence interval (CI): 8.8, 151.9) more common among African Americans. Genotypes known to down-regulate the antiinflammatory IL-10 (IL10-819 T/T and IL10-1082 A/A) are elevated 3.5-fold (95% CI: 1.8, 6.6) and 2.8-fold (95% CI: 1.6, 4.9) in African Americans. Cytokine genotypes found to be more common in African-American women are consistently those that up-regulate inflammation^ref. Many diseases causing premature mortality among African Americans are mediated by the immune system.

Web resources :

Immuno Polymorphism Database (IPD) : KIR, MHC, human platelet antigens (HPA) and European Searchable Tumour cell Line Database (ESTDAB)
American Society for Histocompatibility and Immunogenetics (ASHI)
British Society for Histocompatibility and Immunogenetics (BSHI)
European Federation for Immunogenetics (EFI)
Immunogenetics @ University of Illinois at Urbana-Champaign

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