MHC class I proteins form a functional receptor on most nucleated cells of the body. There are 3 major and 3 minor MHC class I genes in<unk> . Major MHC class I *<unk> -A *<unk> -B *<unk> -C Minor genes are<unk> -E,<unk> -F and<unk> -G. β2-microglobulin binds with major and minor gene subunits to produce a heterodimer. Illustration of an<unk> -DQ molecule (magenta and blue) with a bound ligand (yellow) floating on the plasma membrane of the cell. There are 3 major and 2 minor MHC class II proteins encoded by the<unk> . The genes of the class II combine to form heterodimeric (αβ) protein receptors that are typically expressed on the surface of<unk> -presenting cells. Major MHC class II proteins only occur on<unk> -presenting cells, B cells, and T cells. *<unk> -DP * α-chain encoded by<unk> -DPA1 locus * β-chain encoded by<unk> -DPB1 locus *<unk> -DQ * α-chain encoded by<unk> -DQA1 locus * β-chain encoded by<unk> -DQB1 locus *<unk> -DR * α-chain encoded by<unk> -DRA locus * 4 β-chains (only 3 possible per person), encoded by<unk> -DRB1, DRB3, DRB4, DRB5 loci The other MHC class II proteins, DM and DO, are used in the internal processing of<unk> s, loading the<unk> ic peptides generated from pathogens onto the<unk>  molecules of<unk> -presenting cell. Nomenclature Modern<unk>  alleles are typically noted with a variety of levels of detail. Most designations begin with<unk> - and the locus name, then * and some (even) number of digits specifying the allele. The first two digits specify a group of alleles, also known as supertypes. Older typing methodologies often could not completely distinguish alleles and so stopped at this level. The third through fourth digits specify a nonsynonymous allele. Digits five through six denote any synonymous mutations within the coding frame of the gene. The seventh and eighth digits distinguish mutations outside the coding region. Letters such as L, N, Q, or S may follow an allele's designation to specify an expression level or other non-genomic data known about it. Thus, a completely described allele may be up to 9 digits long, not including the<unk> -prefix and locus notation. Variability Codominant expression of<unk>  genes. MHC loci are some of the most genetically variable coding loci in mammals, and the<unk> <unk>  loci are no exceptions. Despite the fact that the<unk>  population went through a constriction several times during its history that was capable of fixing many loci, the<unk>  loci appear to have survived such a constriction with a great deal of variation. Of the 9 loci mentioned above, most retained a dozen or more allele-groups for each locus, far more preserved variation than the vast majority of<unk>  loci. This is consistent with a heterozygous or balancing selection coefficient for these loci. In addition, some<unk>  loci are among the fastest-evolving coding regions in the<unk>  genome. One mechanism of diversification has been noted in the study of Amazonian tribes of South America that appear to have undergone intense gene conversion between variable alleles and loci within each<unk>  gene class. Less frequently, longer-range productive recombinations through<unk>  genes have been noted producing chimeric genes. Six loci have over 100 alleles that have been detected in the<unk>  population. Of these, the most variable are<unk>  B and<unk>  DRB1. As of 2012, the number of alleles that have been determined are listed in the table below. To interpret this table, it is necessary to consider that an allele is a variant of the nucleotide (DNA) sequence at a locus, such that each allele differs from all other alleles in at least one (single nucleotide polymorphism, SNP) position. Most of these changes result in a change in the amino acid sequences that result in slight to major functional differences in the protein. There are issues that limit this variation. Certain alleles like DQA1*05:01 and DQA1*05:05 encode proteins with identically processed products. Other alleles like DQB1*0201 and DQB1*0202 produce proteins that are functionally similar. For class II (DR, DP and DQ), amino acid variants within the receptor's peptide-binding cleft tend to produce molecules with different binding capability. However, the gene frequencies of the most common alleles (>5%) of<unk> -A, -B, -C and<unk> -DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 from South America have been reported from the typing and sequencing carried out in genetic diversity studies and cases and controls. In addition, information on the allele frequencies of<unk> -I and<unk> -II genes for the European population has been compiled. In both cases the distribution of allele frequencies reveals a regional variation related with the history of the populations. Tables of variant alleles Number of variant alleles at class I loci according to the IMGT-HLA database, last updated October 2018: MHC class I locus # Major<unk> s<unk>  A 4,340<unk>  B 5,212<unk>  C 3,930 Minor<unk> s<unk>  E 27<unk>  F 31<unk>  G 61 Number of variant alleles at class II loci (DM, DO, DP, DQ, and DR): MHC class II<unk>  -A1 -B1 -B3 to -B51 Theor. possible locus # # # combinations DM- 7 13 91 DO- 12 13 156 DP- 67 1,014 16,036 DQ- 95 1,257 34,528 DR- 7 2,593 312 11,431 1DRB3, DRB4, DRB5 have variable presence in<unk> s Sequence feature variant type (SFVT) The large extent of variability in<unk>  genes poses significant challenges in investigating the role of<unk>  genetic variations in diseases. Disease association studies typically treat each<unk>  allele as a single complete unit, which does not illuminate the parts of the molecule associated with disease. Karp D. R. et al. describes a novel sequence feature variant type (SFVT) approach for<unk>  genetic analysis that categorizes<unk>  proteins into biologically relevant smaller sequence features (SFs), and their variant types (VTs). Sequence features are combinations of amino acid sites defined based on structural information (e.g., beta-sheet 1), functional information (e.g., peptide<unk> -binding), and polymorphism. These sequence features can be overlapping and continuous or discontinuous in the linear sequence. Variant types for each sequence feature are defined based upon all known polymorphisms in the<unk>  locus being described. SFVT categorization of<unk>  is applied in genetic association analysis so that the effects and roles of the epitopes shared by several<unk>  alleles can be identified. Sequence features and their variant types have been described for all classical<unk>  proteins; the international repository of<unk>  SFVTs will be maintained at IMGT/HLA database. A tool to convert<unk>  alleles into their component SFVTs can be found on the Immunology Database and Analysis Portal (ImmPort) website. Common, well-documented and rare alleles Although the number of individual<unk>  alleles that have been identified is large, approximately 40% of these alleles appear to be unique, having only been identified in single individuals. Roughly a third of alleles have been reported more than three times in unrelated individuals. Because of this variation in the rate at which of individual<unk>  alleles are detected, attempts have been made to categorize alleles at each expressed<unk>  locus in terms of their prevalence. The result is a catalog of common and well-documented (CWD)<unk>  alleles, and a catalogue of rare and very rare<unk>  alleles. Common<unk>  alleles are defined as having been observed with a frequency of at least 0.001 in reference populations of at least 1500 individuals. Well-documented<unk>  alleles were originally defined as having been reported at least three times in unrelated individuals, and are now defined as having been detected at least five times in unrelated individuals via the application of a sequence-based typing (SBT) method, or at least three times via a SBT method and in a specific haplotype in unrelated individuals. Rare alleles are defined as those that have been reported one to four times, and very rare alleles as those reported only once. Table of<unk>  alleles in each prevalence category While the current CWD and rare or very rare designations were developed using different datasets and different versions of the IMGT/HLA Database, the approximate fraction of alleles at each<unk>  locus in each category is shown below.<unk> Locus No. commonalleles % commonalleles No. well-documentedalleles % well-documentedalleles No. rarealleles % rarealleles No. very rarealleles % very rarealleles % allelescategorized A 68 3.4% 178 8.8% 145 21.5% 280 41.6% ~75% B 125 4.8% 242 9.3% 190 17.6% 468 43.5% ~75% C 44 2.8% 102 6.6% 77 21.4% 154 42.8% ~74% DRB1 79 6.8% 147 12.7% 133 22.7% 206 35.2% ~77% DRB3 5 8.6% 7 12.1% ~21% DRB4 6 40.0% 2 13.3% ~53% DRB5 5 25.0% 3 15.0% ~40% DQA1 15 31.9% 4 8.5% 9 26.5% 7 20.6% ~88% DQB1 22 12.5% 8 4.5% 26 28.9% 42 45.2% ~91% DPA1 6 17.6% 0 0.0% 4 14.8% 15 55.6% ~88% DPB1 40 28.8% 14 9.0% 29 22.7% 29 32.8% ~90% All Loci 415 5.3% 707 9.0% 613 20.6% 1214 40.8% ~76% Examining<unk>  types Serotype and allele names There are two parallel systems of nomenclature that are applied to<unk> . The first, and oldest, system is based on serological (antibody based)
Human leukocyte antigen
Hh blood group
Anton blood group antigen
Rh blood group system
Blood type
Lan blood group system
Isoantibodies
Human blood group systems