Gene map of the extended human
MHC

Horton, Roger W.; Wilming, Laurens G.; Rand, Vikki; Lovering, Ruth C.; Bruford, Elspeth A.; Khodiyar, Varsha; Lush, Michael; Povey, Sue; Talbot, C. Conover; Wright, Mathew W.; Wain, Hester; Trowsdale, John; Ziegler, Andreas; Beck, Stephan

doi:10.1038/nrg1489

Cited by 993 publications

(820 citation statements)

References 92 publications

Supporting

Mentioning

772

Contrasting

Unclassified

Order By: Relevance

“…19 Some genes are duplicated, one copy of each being functional in the case of DP and DQ. Depending on the individual, 19 genes may be found in the 0.9 Mb of sequence spanned by the class II region including eight pseudogenes.…”

Section: Mhc Class II Genes and Their Expressionmentioning

confidence: 99%

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

et al. 2009

View full text Add to dashboard Cite

Major histocompatibility complex (MHC) class II molecules are central to adaptive immune responses and maintenance of selftolerance. Since the early 1970s, the MHC class II region at chromosome 6p21 has been shown to be associated with a remarkable number of autoimmune, inflammatory and infectious diseases. Given that a full explanation for most MHC class II disease associations has not been reached through analysis of structural variation alone, in this review we examine the role of genetic variation in modulating gene expression. We describe the intricate architecture of the MHC class II regulatory system, indicating how its unique characteristics may relate to observed associations with disease. There is evidence that haplotypespecific variation involving proximal promoter sequences can alter the level of gene expression, potentially modifying the emergence and expression of key phenotypic traits. Although much emphasis has been placed on cis-regulatory elements, we also examine the role of more distant enhancer elements together with the evidence of dynamic inter-and intra-chromosomal interactions and epigenetic processes. The role of genetic variation in such mechanisms may hold profound implications for susceptibility to common disease.

show abstract

Section: Mhc Class II Genes and Their Expressionmentioning

confidence: 99%

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

et al. 2009

View full text Add to dashboard Cite

show abstract

“…It contains highly polymorphic genes coding for molecules whose role is to present selfand nonself-derived peptide antigens to T cells. The MHC is thus essential in triggering the adaptative immune response [1]. There is a longstanding hypothesis that selection may have led to mating patterns that increase heterozygosity at MHC loci because of improved immune resistance conferred to the offspring conceived through such matings.…”

Section: Introductionmentioning

confidence: 99%

MHC‐dependent mate choice in humans: Why genomic patterns from the HapMap European American dataset support the hypothesis

Laurent

Chaix

2012

BioEssays

View full text Add to dashboard Cite

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC‐dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC‐dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC‐dependent mate choice in some human populations.

show abstract

“…The extended class I region harbors several T1D candidate genes involved in immunological processes, 16 including the PRSS16 gene, a cluster of seven butyrophilin (BTN) genes that are members of the immunoglobulin superfamily, 17 and zinc-finger protein genes encoding transcriptional regulators involved in cell growth and differentiation. 18 The PRSS16 gene is predominantly expressed in the cortical epithelial cells of the thymus, and has been suggested to play a role in the positive selection of T cells or in T-cell regulation.…”

Section: Introductionmentioning

confidence: 99%

Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex

et al. 2009

View full text Add to dashboard Cite

The high-risk human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 alleles cannot explain the entire type 1 diabetes (T1D) association observed within the extended major histocompatibility complex. We have earlier identified an association with D6S2223, located 2.3 Mb telomeric of HLA-A, on the DRB1*03-DQA1*0501-DQB1*0201 haplotype, and this study aimed to fine-map the associated region also on the DRB1*0401-DQA1*03-DQB1*0302 haplotype, characterized by less extensive linkage disequilibrium. To exclude associations secondary to DRB1-DQA1-DQB1 haplotypes, 205 families with at least one parent homozygous for these loci, were genotyped for 137 polymorphisms. We found novel associations on the DRB1*0401-DQA1*03-DQB1*0302 haplotypic background with eight single nucleotide polymorphisms (SNPs) located within or near the PRSS16 gene. In addition, association at the butyrophilin (BTN)-gene cluster, particularly the BTN3A2 gene, was observed by multilocus analyses. We replicated the associations with SNPs in the PRSS16 region and, albeit weaker, to the BTN3A2 region, in an independent material of 725 families obtained from the Type 1 Diabetes Genetics Consortium. It is important to note that these associations were independent of the HLA-DRB1-DQA1-DQB1 genes, as well as of associations observed at HLA-A, -B and -C. Taken together, our results identify PRSS16 and BTN3A2, two genes thought to play important roles in regulating the immune response, as potentially novel susceptibility genes for T1D.

show abstract

Gene map of the extended human MHC

Cited by 993 publications

References 92 publications

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

MHC‐dependent mate choice in humans: Why genomic patterns from the HapMap European American dataset support the hypothesis

Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex

Contact Info

Product

Resources

About