Commentary| Volume 72, ISSUE 8, P615-616, October 15, 2012

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The Genes in the Major Histocompatibility Complex as Risk Factors for Schizophrenia: De Omnibus Dubitandum

  • Thomas Lehner
    Address correspondence to Thomas Lehner, Ph.D., Director, Office of Genomic Research Coordination/National Institute of Mental Health/National Institutes of Health/Department of Health and Human Services, Bethesda, Maryland 20892
    National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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      The major histocompatibility complex (MHC) is an approximately 4 megabase region located on the short arm of chromosome 6 (6p21); it is also known as the human leukocyte antigen (HLA) superlocus. MHC encodes the classical and transplantation HLA genes and many other genes with essential roles for immune function and cellular processes including genes that are important for nervous system development and function. Although the MHC represents only a very small part (about .1%) of the human genome its properties can easily be described as extreme and intricate: most complex, most gene dense, most polymorphic, second largest contiguous sequence, containing the most disease associations, and most difficult to analyze. Overall, the MHC contains a minimum of 253 identified genes: 133 protein coding, 19 gene candidates, 22 noncoding, and 79 pseudogenes. MHC is historically divided into three regions, and HLA genes are distributed over the class I and class II regions, which in turn are separated by .7 MB of DNA of class III region genes, which have no known function in immunity. There are 19 HLA loci and 19 HLA class 2 loci that both include the classical HLA genes all interspersed in a complex highly polymorphic genomic sequence in which many loci are in almost complete linkage disequilibrium, and the region is full of interspersed repeats (
      • Shiina T.
      • Hosomichi K.
      • Inoko H.
      • Kulski J.K.
      The HLA genomic loci map: expression, interaction, diversity and disease.
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