Disease relevance of HCG9

• Two subgenomic regions within the major histocompatibility complex, the alpha and beta blocks, contain members of the multicopy gene families HLA class I, human endogenous retroviral sequence (HERV-16; previously known as P5 and PERB3), hemochromatosis candidate genes (HCG) (II, IV, VIII, IX), 3.8-1, and MIC (PERB11) [1].
• Each bead contains or contained sequences representing Class I, PERB11 (MHC Class I chain related (MIC) and human endogenous retrovirus (HERV) 16 [2].
• The Human Leukocyte Antigen Class I Region Is Associated with EBV-Positive Hodgkin's Lymphoma: HLA-A and HLA Complex Group 9 Are Putative Candidate Genes [3].
• These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis [4].
• Susceptibility to autoimmune diseases, such as IDDM, has been associated functionally with two members of a newly described multigene family called PERB11 [5].

High impact information on HCG9

• The human major histocompatibility complex (MHC) is characterized by polymorphic multicopy gene families, such as HLA and MIC (PERB11); duplications; insertions and deletions (indels); and uneven rates of recombination [6].
• On the 62.1 haplotype, the alpha block consists of at least 10 duplicated segments that predominantly contain pseudogenes and gene fragments of the HLA class I and MIC (PERB11) gene families [1].
• These include sequences belonging to the P5, BAT1, and PERB11 gene families as well as HLA class I gene sequences [7].
• Phylogenetic analysis of PERB11 alpha-domain sequences demonstrates relationships with HLA-B cross-reactive serogroups [8].
• Coevolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication [9].

Biological context of HCG9

• After Southern blot analysis, the corresponding cDNA clone was found to belong to a new multigene family whose members are dispersed throughout the HLA class I region and are closely associated with members of another recently described multigene family designated PERB11 [10].
• Shared Alu elements and other retroelements allowed the duplicated segments to be classified into five distinct groups (A to E) that could be further distilled down to an ancient preduplication segment containing a HLA and PERB11 gene, an endogenous retrovirus (HERV-16), and distinctive retroelements [9].
• The associated SNPs are located nearby two putative candidate genes: HLA-A and HLA complex group 9 [3].
• From direct comparison of amino acid sequences, it is concluded that PERB11 is a distinct molecule more closely related to nonmammalian than known mammalian MHC class I molecules [11].
• Furthermore, not all of the potential glycosylation sites suggested by the PERB11 sequences appear viable [12].

Anatomical context of HCG9

• The partial cDNA sequence of PERB11 was obtained from poly-A RNA derived from skeletal muscle [11].

Associations of HCG9 with chemical compounds

• Duplication of segments within the MHC has led to numerous multicopy families such as class I, class II, C4 and MIC (PERB11) [13].

Other interactions of HCG9

• A new non-HLA multigene family associated with the PERB11 family within the MHC class I region [10].
• Southern analysis of genomic DNA and overlapping YAC clones, covering the region from BAT1 to HLA-F, indicated that there are at least five copies of PERB11, four of which are located within this region of the MHC [11].
• There are at least five copies of MIC (PERB11) in humans, but MICA (PERB11.1) appears to have been deleted from the chimpanzee [13].
• PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers [4].
• The putative amino acid sequence of PERB11 shares approximately 30% identity to MHC class I molecules from various species, including reptiles, chickens, and frogs, as well as to other MHC class I-like molecules, such as the IgG FcR of the mouse and rat and the human Zn-alpha 2-glycoprotein [11].

Analytical, diagnostic and therapeutic context of HCG9

• Genomic sequence analysis of PERB11 from five MHC ancestral haplotypes (AH) indicated that the gene is polymorphic at both DNA and protein level [11].

References