HLA-A2

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major histocompatibility complex (human), class I, A2
Alleles A*0201 </br> A*0202 </br> A*0203 </br> A*0205 </br> A*0206 </br> A*0207 </br> A*0211
Structure (See HLA-A)
Identifiers
*0201 *0202 *0203 *0205 *0206 *0207 *0211
Symbol(s) HLA-A2
EBI-HLA A*0201
EBI-HLA A*0202
EBI-HLA A*0203
EBI-HLA A*0205
EBI-HLA A*0206
EBI-HLA A*0207
EBI-HLA A*0211
Shared data
Locus chr.6 6p21.31

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Overview

HLA-A2 (A2) is an HLA-A serotype. The serotype identifies the more common HLA-A*0201, *0202, *0203, *0206, and *0207 gene products. A*02 is globally common, but A*0201 is at high frequencies in Northern Asia and North America. A2 is the most diverse serotye, showing diversity in Eastern Africa and Southwest Asia. While the frequency of A*0201 in Northern Asia is high, its diversity is limited to A*0201 the less common asian variants A*0203, A*0206.

Serotype

A2 serotype recognition of Some HLA A*02 allele-group gene products[1]
A*02 A2 Sample
allele  %  % size (N)
*0201 98 6315
*0202 81 859
*0203 64 472
*0204 78 28
*0205 81 462
*0206 68 636
*0207 80 135
*0211 74 228

The serotyping for the most abundant A*02 alleles is good. For A*0203, A*0206, A*0207 serotyping is borderline useful. There is a separate serotyping for A203 and A210. There are over 125 alleles identified (mostly by sequence homology) as being A2, of those 8 are nulls, and a large majority have unknown serotypes.

Disease Associations

By serotype

A2 Associated with spontaneous abortion in A2+/A[other] phenotypic children[2]

By haplotype

A*02:Cw*16 is associated with increased higher viral load in HIV[3]

A2-B Haplotypes

A2-B7 (Node in Netherlands) A2-B5

  • A2-B51
  • A2-B52

A2-B8
A2-B13
A2-B14

  • A2-B64
  • A2-B65

A2-B15

  • A2-B62
  • A2-B63
  • A2-B70,71,75,76
  • A2-B46 (Node in Southern China, may be most abundant haplotype)

A2-B16

A2-B18
A2-B27
A2-B35
A2-B37 A2-B39 (Node in North American Amerinds)
A2-B40

  • A2-B60
  • A2-B61

A2-Cw5-B44

HLA A2-B44 haplotype frequencies
freq Rank in
ref. Population (%) Pop.
[4] Cornish 11.4 1 1
[5] Ireland 9.2 2
[6] Northern Ireland 8.0 1 2
[4] Sweden 7.2 2
[7] Swiss 6.9 2
[4] Polish 6.2 1
[4] Spanish 5.9 1
[4] Ukraine 5.9 1
[8] Dutch Netherlands 5.9 3
[4] Dane 4.8 1
[4] Czech 4.7 3
[4] Basque 4.7 3
[4] Greek 4.5 3
[4] Yugoslavian 4.4
[4] Hungarian 3.5
[4] British 2.6 4
[1] Romania 2.5
[4] Austria 2.4
1Cw*0501 (Eur.)

A2-Cw5-B44 is the multi-serotype designation for the haplotype HLA-A*0201:C*0501:B*4402, the class I portion, of an ancetral haplotype (A2-B44-DR4-DQ8). The full haplotype is (for relative distances see Human leukocyte antigens:

A*0201 : C*0501 : B*4402 : DRB1*0401 : DQA1*0301 : DQB1*0302

Another haplotype that is more common in Central Europe is the (A2-B44-DR7-DQ2)

A*0201 : C*0501 : B*4402 : DRB1*0701 : DQA1*0201 : DQB1*0202

Over northwestern Europe A2-B44 shows a single common ancestor which contributed the Cw5 allele to the haplotype. The haplotype appears to have been introduced early in european prehistoric period, frequencies of the haplotype generally correlate with A1-Cw7-B8 and A2-B7. The haplotype is considerably more equilibrated relative to A1-B8 and a possible reason is gene flow from iberia or the east with related haplotypes after initial migrations.

A2-Cw11(1)-B46

HLA A2-B46 haplotype frequencies
freq Rank in
ref. Population (%) Pop.
[4] Buyi 16.6 1 1
[4] Miao 13.6 1
[4] Singapore</br>(chinese) 11.4 2
[9] Chaoshan 10.1 1
[4] Southern Han 7.8 2
[4] VietNam 7.8 1
[4] Thai 7.2 1
[4] Thai Chinese 4.0
[4] Japanese 3.3 4
[4] Li 3.0
[4] Korea 2.8
[4] Uygar 2.7
[4] Manchu 2.6
[4] Inner Mong. 1.9
[4] Northern Han 1.8
1 highest freq. A-B hap in Asia.

This haplotype is rather unique in several regards, first and most importantly the B46 serotype is not from Africa, this distinquishes it from every other known B serotype. It is the result of a recombination event between B62(B*1501) and an HLA-C allele within Asia. This event happened recently as there is only one major allele and minor alleles are at trace frequencies. There has been some recombination between this haplotype, A24 and A11 bearing alleles, probably in a local (or tribal population). B46 is found whereever asian wet-rice farming peoples have traveled and is found at low frequencies in non-farming indigeonous groups. The one exception is the Ninhvet of Siberia and the Eastern Tlinglet of Alaska. This B46 contribution appears to have been recent. Because of the numbers of people represented by the sample groups, and its relative high frequency in those group A2-B46 is one of the most frequent, if not the most frequent A-B haplotype in the world, even though it is absent from the indigeonous populations of most peoples in the world.

The most common haplotype, and probably the ancestral haplotype given its distribution from the Ninhivet to Indonesia is:

A*0207 : C*0102 : B*4601 : DRB1*0901 : DQA1*0302 : DQB1*0303

A different haplotype that is more common in Korea and Japan is

A*0207 : C*0102 : B*4601 : DRB1*0803 : DQA1*0103 : DQB1*0601

B46, or a closely linked allele may have been under positive selection in rice farmers of asia.

References

  1. derived from IMGT/HLA
  2. Komlos L, Klein T, Korostishevsky M (2007). "HLA-A2 class I antigens in couples with recurrent spontaneous abortions". Int. J. Immunogenet. 34 (4): 241–6. PMID 17627758. doi:10.1111/j.1744-313X.2007.00682.x. 
  3. Tang J, Tang S, Lobashevsky E, Myracle A, Fideli U, Aldrovandi G, Allen S, Musonda R, Kaslow R (2002). "Favorable and unfavorable HLA class I alleles and haplotypes in Zambians predominantly infected with clade C human immunodeficiency virus type 1.". J Virol. 76 (16): 8276–84. PMID 12134033. 
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 4.23 4.24 4.25 4.26 Sasazuki, Takehiko; Tsuji, Kimiyoshi; Aizawa, Miki (1992). HLA 1991: proceedings of the eleventh International Histocompatibility Workshop and Conference, held in Yokohama, Japan, 6-13 November, 1991. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-262390-7. 
  5. Finch T, Lawlor E, Borton M, Barnes C, McNamara S, O'Riordan J, McCann S, Darke C (1997). "Distribution of HLA-A, B and DR genes and haplotypes in the Irish population.". Exp Clin Immunogenet. 14 (4): 250–63. PMID 9523161. 
  6. Middleton D, Williams F, Hamill M, Meenagh A (2000). "Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy.". Hum Immunol. 61 (12): 1285–97. PMID 11163085. 
  7. Grundschober C, Sanchez-Mazas A, Excoffier L, Langaney A, Jeannet M, Tiercy J (1994). "HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities.". Eur J Immunogenet. 21 (3): 143–57. PMID 9098428. 
  8. Schipper R, Schreuder G, D'Amaro J, Oudshoorn M (1996). "HLA gene and haplotype frequencies in Dutch blood donors.". Tissue Antigens. 48 (5): 562–74. PMID 8988539. 
  9. Hu SP, Luan JA, Li B; et al. (2007). "Genetic link between Chaoshan and other Chinese Han populations: Evidence from HLA-A and HLA-B allele frequency distribution". Am. J. Phys. Anthropol. 132 (1): 140–50. PMID 16883565. doi:10.1002/ajpa.20460. 



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