Major Histocompatibility Complex Genomics and Human Disease
By J. Trowsdale, J. Knight. Annual review of genomics and human genetics (Print), 2013
685 citations recorded by the source corpus.
Over several decades, various forms of genomic analysis of the human major histocompatibility complex (MHC) have been extremely successful in picking up many disease associations. This is to be expected, as the MHC region is one of the most gene-dense and polymorphic stretches of human DNA. It also encodes proteins critical to immunity, including several controlling antigen processing and presentation. Single-nucleotide polymorphism genotyping and human leukocyte antigen (HLA) imputation now permit the screening of large sample sets, a technique further facilitated by high-throughput sequencing. These methods promise to yield more precise contributions of MHC variants to disease. However, interpretation of MHC-disease associations in terms of the functions of variants has been problematic. Most studies confirm the paramount importance of class I and class II molecules, which are key to resistance to infection. Infection is likely driving the extreme variation of these genes across the human population, but this has been difficult to demonstrate. In contrast, many associations with autoimmune conditions have been shown to be specific to certain class I and class II alleles. Interestingly, conditions other than infections and autoimmunity are also associated with the MHC, including some cancers and neuropathies. These associations could be indirect, owing, for example, to the infectious history of a particular individual and selective pressures operating at the population level.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/2c5bbd0df1c418d22e52a47eed82a246a3104717
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In Immunology
Citations in the corpus
- IPD-IMGT/HLA Database (2019, background): “The MHC is a region in the genome of all jawed vertebrates, and encodes core components of the immune system (27).”
- HLA variation and disease (2018, background): “Since then, the MHC has been established as the region of the genome that is associated with the greatest number of human diseases 2 .”