PMID- 23875801
OWN - NLM
STAT- MEDLINE
DCOM- 20131202
LR  - 20220310
IS  - 1545-293X (Electronic)
IS  - 1527-8204 (Print)
IS  - 1527-8204 (Linking)
VI  - 14
DP  - 2013
TI  - Major histocompatibility complex genomics and human disease.
PG  - 301-23
LID - 10.1146/annurev-genom-091212-153455 [doi]
AB  - 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.
FAU - Trowsdale, John
AU  - Trowsdale J
AD  - Department of Pathology and Cambridge Institute for Medical Research, University 
      of Cambridge, Cambridge CB2 1QP, United Kingdom; email: jt233@cam.ac.uk.
FAU - Knight, Julian C
AU  - Knight JC
LA  - eng
GR  - 281824/ERC_/European Research Council/International
GR  - 075491/Z/04/WT_/Wellcome Trust/United Kingdom
GR  - G1001708/MRC_/Medical Research Council/United Kingdom
GR  - 98082/MRC_/Medical Research Council/United Kingdom
GR  - 074318/WT_/Wellcome Trust/United Kingdom
GR  - 090532/WT_/Wellcome Trust/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 100140/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130715
PL  - United States
TA  - Annu Rev Genomics Hum Genet
JT  - Annual review of genomics and human genetics
JID - 100911346
SB  - IM
MH  - Animals
MH  - Biological Evolution
MH  - *Genetic Predisposition to Disease
MH  - Genomics
MH  - Humans
MH  - *Major Histocompatibility Complex
MH  - Polymorphism, Single Nucleotide
PMC - PMC4426292
MID - EMS63323
OID - NLM: EMS63323
EDAT- 2013/07/24 06:00
MHDA- 2013/12/16 06:00
PMCR- 2015/05/11
CRDT- 2013/07/24 06:00
PHST- 2013/07/24 06:00 [entrez]
PHST- 2013/07/24 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2015/05/11 00:00 [pmc-release]
AID - 10.1146/annurev-genom-091212-153455 [doi]
PST - ppublish
SO  - Annu Rev Genomics Hum Genet. 2013;14:301-23. doi: 
      10.1146/annurev-genom-091212-153455. Epub 2013 Jul 15.