HLA-A33 explained

A33 frequencies

HLA A*3301 frequencies
freq
ref. Population (%)
[1] Pakistan Karachi Parsi12.2
[2] Portugal North7.6
[3] Tunisia6.1
[4] Morocco Nador Metalsa5.5
Mongolia Buriat4.6
[5] Guinea Bissau4.6
[6] Jordan Amman3.5
Cape Verde NW Islands3.2
Portugal Centre3.0
[7] Iran Baloch2.8
[8] Pakistan Baloch2.4
France South East2.3
Sudanese1.8
Japan Okinawa Ryukyuan1.8
[9] Mali Bandiagara1.8
[10] Bulgaria1.8
Pakistan Kalash1.7
Uganda Kampala1.5
[11] Georgia Svaneti1.3
Kenya Luo1.3
[12] Oman1.3
Zambia Lusaka1.2
[13] China Guangdong Meizhou1.0
Romanian1.0
Croatia1.0
[14] China Qinghai Hui0.9
Czech Republic[15] 0.9
Kenya 0.7
[16] Ireland Northern0.7
Singapore Chinese0.6
[17] Cameroon Bamileke0.6
[18] India North Delhi0.5
Georgia Tbilisi0.5
Belgium0.5
Cameroon Beti0.3
Kenya Nandi0.2

A33 shows two different distributions that can be discriminated by subtyping capability of SSP-PCR.

A*3301 distribution

The first distribution appears to have a Western distribution that introgresses into Europe as a result of the post-Neolithic periods. It is commonly found in linkage disequilibration within the A*3301-Cw*0802-B*1402 haplotype which can be extended to DRB1 and DQB1 in certain instances (see below). The source of its general expansion appears to be the Middle East or the Levant, as it is found in the Palestinian population. B14 splits into B64 (B*1401) and B65 (B*1402).

A*3303 distribution

HLA A*3303 frequencies
freq
ref. Population (%)
Cameroon Baka25.0
Cameroon Sawa23.1
India West Bhils18.0
Pakistan Burusho17.9
[19] South Korea (3)16.3
India West Parsis14.0
Singapore Thai13.3
India Mumbai Marathas13.0
[20] Japan12.8
Pakistan Baloch12.7
China South Han11.5
Singapore Riau Malay10.9
Singapore Chinese10.1
Hong Kong Chinese10.0
[21] Chaoshan 9.8
Mali Bandiagara9.4
China Inner Mongolia9.3
Singapore Chinese Han9.3
Singapore Javan9.0
[22] India North Hindus8.7
Guinea Bissau8.5
Taiwan Minnan8.3
Taiwan Hakka8.2
[23] Senegal Mandenka8.1
Pakistan Brahui8.0
Pakistan Sindhi7.6
Russia Tuvan7.1
Pakistan Pathan7.1
South Africa Natal Tamil7.0
Pakistan Karachi Parsi6.7
[24] India Tamil Nadu Nadar6.6
Israel Jews6.4
India Andhra Pradesh Golla6.3
[25] China North Han6.2
[26] China Beijing Tianjian6.2
India New Delhi6.1
Pakistan Kalash5.8
Iran Baloch5.6
China Qinghai Hui5.5
China Guangzhou5.4
Cameroon Bamileke4.5
[27] China Yunnan Nu4.4
China Guangxi Maonan4.2
China Guangdong Meizhou4.0
Cape Verde SW Islands4.0
Taiwan Pazeh3.6
Uganda Kampala3.1
China Beijing3.0
India Khandesh Pawra3.0
Cameroon Yaounde2.8
Sudanese2.5
Zimbabwe Harare Shona2.4
Cape Verde NW Islands2.4
Cameroon Beti2.3
Oman2.1
[28] China Tibet1.6
Croatia1.3
Romanian1.2
China Yunnan Lisu1.1
Arab Druse1.0
Georgia Tbilisi1.0
Belgium1.0
Kenya Luo0.9
[29] Lakota Sioux0.5
Australian Indig. Cape York0.5
Tunisia0.5
South African Natal Zulu0.5
Kenya 0.3
Ireland Northern0.3
Kenya Nandi0.2
The distribution of A*3303 varies across populations. It has been found at relatively low frequencies in samples of East Asian populations (Korean, 16.49; Javanese, 15.61%; Vietnamese, 11.5%).[30] These frequencies increase in studies of populations from Western India, such as Maharashtra.[31]

A33 haplotypes

A33-Cw8-B14-DR1-DQ5

HLA A*33-B14 frequencies
freq
ref. Population (%)
Parsis (Pakistan)4.4
[32] Sardinian3.0
India West Coast Parsis 3.3[33]
Portuguese2.7
Armenian2.5
Indian2.0
Polish2.0
Ashkenazi Jews1.8
French1.8
Spanish1.7
Albanian1.5
German1.5
Tuscan1.3
Greek1.1
Marathans1.1
Italian1.0

When dealing with haplotypes, if one assumes that linkage disequilibrium is random, then one can estimate the time of equilibration based on the size of the haplotype, the A-B-DR haplotype is over 2 million nucleotides in length. Given this length it is unlikely it spread during the Neolithic period. A more likely guess as to when it spread was the early historic period, with the spread of the Phoenician and Mycenaean culture throughout the mediterranean. Its presence in India, particularly northern India, indicates possible spread of this haplotype within the Black Sea region prior to the migration of Indo-Aryan culture across the Indus River. The specific nomenclature for this type is:

A : C : B : DRB1 : DQA1 : DQB1

A33-B44

HLA A*33-B44 frequencies
freq
ref. Population (%)
Iyers9.6
Korea8.0
Japan6.1
Thais4.7
Parsis (Pakistan)4.4
Bharghavas4.0
Java3.7
Tribals (India)3.0
Chinese (Thailand)2.8
Vietnamese2.7

This haplotype appears to precede A33-B58 in Asia, bringing with it the DR7-DQ2 haplotype.There are two versions of the haplotype, possibly of different origins. It's a good reason why serotyping alone should not be relied upon. The first haplotype is A33-Cw14-B44-DR13-DQ6.4[34]

A : C : B : DRB1 : DQA1 : DQB1 : DPB1

This haplotype is found in Japan and Korea, and it is the most common 5 locus HLA type in Korea, high at 4.2%, 25 times higher than in China. In Japan it is 4.8% and can be extended to DPB1 at 3.6%. While clearly not showing the level of disequilibrium of the Super B8 haplotype, the level of disequilibrium is high, indicating an expansive migration into these regions at some time in the recent past, most likely in the period preceding the Yayoi period of Japan.

A : C : B : DRB1 : DQA1 : DQB1

The second haplotype, like A33-B58 is found in Korea but not in Japan.[19] This haplotypecarries the other common DQ2 haplotype, DQ2.2. The Cw*0701 is found in the A*33-B58 haplotype and is like the result of a recombination between A33-Cw7 and a different B44-DR7 haplotype.These haplotypes indicate that interpreting population relationships by allele or even by low resolution haplotype information is error-prone and suggests the need for high resolutionmultigene haplotype studies.

A33-Cw3-B58-DR3-DQ2

HLA A*33-B58 frequencies
freq
ref. Population (%)
Chinese (Thailand)12.6
Baloch (Pakistan)11.1
Chaoshan (China)8.1
Chinese (Singapore)5.5
Burusho (Pakistan)4.6
Hui4.0
Mongolian3.7
Kalash (Pakistan)3.6
Korea3.5
Yaku3.2
Panthan (Pakistan)3.0
Tribals (India)3.0
Baloch (SE Iran)2.9
Brahui (Pakistan)2.9
Southern Han2.8
Thais2.5
Vietnamese2.3
Inner Mongolian2.2
Miao2.1
West African 2.1
South African1.9
[35] Oman1.6
Sindhi (Pakistan)1.5
Manchu1.2
[36] Sudan1.2
Cameroon Yaounde[37] 1.1
Within eastern Asia A*3303 is in linkage disequilibrium with on haplotype in particular, the specific genetic makeup is:

A : C : B : DRB1 : DQA1 : DQB1

It is interesting that the Cw allele in the Pakistani population is the same as the allele in the east Asian population C*0302. 8.3 of 11.1% of the A33-B58 in the Baloch Pakistani can is linked to DR3 and presumably DQ2.5 (There are few exceptions outside of Africa). This extends a haplotype the forms a semicircle around the Indian subcontinent indicating a substantive and relatively recent genetic relationship. The Parsis of Pakistan lack A33-B58, as with groups to the far west of Pakistan. The A33-B58-DR3-DQ2 haplotype appears to have originated in whole from West Africa, with current possibilities for Sudan or Northern Ethiopia as points of exit from Africa and a migration by the Indian Ocean to the western side of the Indus River.

A33-Cw7-B58-DR13-DQ6

Within eastern Asia A*3303 is in linkage disequilibrium with on haplotype in particular, the specific genetic makeup is:

A : C : B : DRB1 : DQA1 : DQB1

This haplotype is composed of genes most frequent in parts of western Africa. This includes the A*3303, B*5801, DRB1*1302, and DQB1*0609. The DRB1*0609 haplotype in nodal in east/central Africa in the Ugandan, Rwanda, Congo, Cameroon whereas the allele is at low frequencies in Western Europe, and its distribution is also consistent with a migration from east Africa direct to the Lower Indus River.

Notes and References

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  2. Middleton D, Menchaca L, Rood H, Komerofsky R . New allele frequency database. Tissue Antigens . 61 . 5 . 403–7 . 2003 . 12753660 . 10.1034/j.1399-0039.2003.00062.x . free .
  3. Ayed K, Ayed-Jendoubi S, Sfar I, Labonne MP, Gebuhrer L . HLA class-I and HLA class-II phenotypic, gene and haplotypic frequencies in Tunisians by using molecular typing data . Tissue Antigens . 64 . 4 . 520–32 . 2004 . 15361135 . 10.1111/j.1399-0039.2004.00313.x.
  4. Piancatelli D, Canossi A, Aureli A, etal . Human leukocyte antigen-A, -B, and -Cw polymorphism in a Berber population from North Morocco using sequence-based typing . Tissue Antigens . 63 . 2 . 158–72 . 2004 . 14705987 . 10.1111/j.1399-0039.2004.00161.x .
  5. Spínola H, Bruges-Armas J, Middleton D, Brehm A . HLA polymorphisms in Cabo Verde and Guiné-Bissau inferred from sequence-based typing . Hum. Immunol. . 66 . 10 . 1082–92 . 2005 . 16386651 . 10.1016/j.humimm.2005.09.001.
  6. Sánchez-Velasco P, Karadsheh NS, García-Martín A, Ruíz de Alegría C, Leyva-Cobián F . Molecular analysis of HLA allelic frequencies and haplotypes in Jordanians and comparison with other related populations . Hum. Immunol. . 62 . 9 . 901–9 . 2001 . 11543892 . 10.1016/S0198-8859(01)00289-0 .
  7. Farjadian S, Naruse T, Kawata H, Ghaderi A, Bahram S, Inoko H . Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan . Tissue Antigens . 64 . 5 . 581–7 . 2004 . 15496201 . 10.1111/j.1399-0039.2004.00302.x.
  8. Mohyuddin A, Ayub Q, Qamar R, Khaliq S, Mansoor A, Mehdi SQ . HLA polymorphisms in ethnic groups from Pakistan . Transplant. Proc. . 31 . 8 . 3350–1 . 1999 . 10616502 . 10.1016/S0041-1345(99)00821-0 .
  9. Cao K, Moormann AM, Lyke KE, etal . Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci . Tissue Antigens . 63 . 4 . 293–325 . 2004 . 15009803 . 10.1111/j.0001-2815.2004.00192.x .
  10. Ivanova M, Rozemuller E, Tyufekchiev N, Michailova A, Tilanus M, Naumova E . HLA polymorphism in Bulgarians defined by high-resolution typing methods in comparison with other populations . Tissue Antigens . 60 . 6 . 496–504 . 2002 . 12542743 . 10.1034/j.1399-0039.2002.600605.x .
  11. Sánchez-Velasco P, Leyva-Cobián F . The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations . Tissue Antigens . 58 . 4 . 223–33 . 2001 . 11782273 . 10.1034/j.1399-0039.2001.580402.x .
  12. Middleton D, Williams F, Meenagh A, etal . Analysis of the distribution of HLA-A alleles in populations from five continents . Hum. Immunol. . 61 . 10 . 1048–52 . 2000 . 11082518 . 10.1016/S0198-8859(00)00178-6 .
  13. Chen S, Li W, Hu Q, Liu Z, Xu Y, Xu A . Polymorphism of HLA class I genes in Meizhou Han population of Guangdong, China . International Journal of Immunogenetics . 34 . 2 . 131–6 . 2007 . 17373939 . 10.1111/j.1744-313X.2007.00669.x. 25192660 .
  14. Hong W, Chen S, Shao H, Fu Y, Hu Z, Xu A . HLA class I polymorphism in Mongolian and Hui ethnic groups from Northern China . Hum. Immunol. . 68 . 5 . 439–48 . 2007 . 17462512 . 10.1016/j.humimm.2007.01.020.
  15. Bendukidze N, Ivasková E, Zahlavová L, etal . Identification of HLA alleles with low or no cell surface expression in the Czech population . Folia Biol. (Praha) . 49 . 6 . 227–9 . 2003 . 14748437 .
  16. Williams F, Meenagh A, Maxwell AP, Middleton D . Allele resolution of HLA-A using oligonucleotide probes in a two-stage typing strategy . Tissue Antigens . 54 . 1 . 59–68 . 1999 . 10458324 . 10.1034/j.1399-0039.1999.540107.x .
  17. Torimiro JN, Carr JK, Wolfe ND, etal . HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A*2612-B*4407 haplotype . Tissue Antigens . 67 . 1 . 30–7 . 2006 . 16451198 . 10.1111/j.1399-0039.2005.00527.x.
  18. Rani R, Marcos C, Lazaro AM, Zhang Y, Stastny P . Molecular diversity of HLA-A, -B and -C alleles in a North Indian population as determined by PCR-SSOP . International Journal of Immunogenetics . 34 . 3 . 201–8 . 2007 . 17504510 . 10.1111/j.1744-313X.2007.00677.x. 24547295 .
  19. Lee KW, Oh DH, Lee C, Yang SY . Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population . Tissue Antigens . 65 . 5 . 437–47 . 2005 . 15853898 . 10.1111/j.1399-0039.2005.00386.x.
  20. Tokunaga K, Ishikawa Y, Ogawa A, etal . Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes . Immunogenetics . 46 . 3 . 199–205 . 1997 . 9211745 . 10.1007/s002510050262 . 22302364 .
  21. Hu SP, Luan JA, Li B, etal . 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 . 2007 . 16883565 . 10.1002/ajpa.20460.
  22. Rajalingam R, Krausa P, Shilling HG, etal . Distinctive KIR and HLA diversity in a panel of north Indian Hindus . Immunogenetics . 53 . 12 . 1009–19 . 2002 . 11904677 . 10.1007/s00251-001-0425-5. 20035835 .
  23. Sanchez-Mazas A, Steiner QG, Grundschober C, Tiercy JM . The molecular determination of HLA-Cw alleles in the Mandenka (West Africa) reveals a close genetic relationship between Africans and Europeans . Tissue Antigens . 56 . 4 . 303–12 . 2000 . 11098930 . 10.1034/j.1399-0039.2000.560402.x .
  24. Shankarkumar U, Sridharan B, Pitchappan RM . HLA diversity among Nadars, a primitive Dravidian caste of South India . Tissue Antigens . 62 . 6 . 542–7 . 2003 . 14617038 . 10.1046/j.1399-0039.2003.00118.x .
  25. Hong W, Fu Y, Chen S, Wang F, Ren X, Xu A . Distributions of HLA class I alleles and haplotypes in Northern Han Chinese . Tissue Antigens . 66 . 4 . 297–304 . 2005 . 16185325 . 10.1111/j.1399-0039.2005.00474.x.
  26. Yang G, Deng YJ, Hu SN, etal . HLA-A, -B, and -DRB1 polymorphism defined by sequence-based typing of the Han population in Northern China . Tissue Antigens . 67 . 2 . 146–52 . 2006 . 16441486 . 10.1111/j.1399-0039.2006.00529.x.
  27. Chen S, Hu Q, Xie Y, etal . Origin of Tibeto-Burman speakers: evidence from HLA allele distribution in Lisu and Nu inhabiting Yunnan of China . Hum. Immunol. . 68 . 6 . 550–9 . 2007 . 17509456 . 10.1016/j.humimm.2007.02.006.
  28. Chen S, Hong W, Shao H, etal . Allelic distribution of HLA class I genes in the Tibetan ethnic population of China . International Journal of Immunogenetics . 33 . 6 . 439–45 . 2006 . 17117954 . 10.1111/j.1744-313X.2006.00637.x. 34168713 .
  29. Leffell MS, Fallin MD, Hildebrand WH, Cavett JW, Iglehart BA, Zachary AA . HLA alleles and haplotypes among the Lakota Sioux: report of the ASHI minority workshops, part III . Hum. Immunol. . 65 . 1 . 78–89 . 2004 . 14700599 . 10.1016/j.humimm.2003.10.001 .
  30. Zhou . D.-X. . Huang . X.-C. . Wang . X.-F. . Zhang . J. . Wang . H. . Tian . Z. . May 2012 . Association study of human leucocyte antigen-A gene with idiopathic male infertility in Han population of China: Association of HLA-A gene and male infertility . Andrologia . en . 44 . 213–218 . 10.1111/j.1439-0272.2011.01166.x. free .
  31. Shankarkumar . Umapathy . Ghosh . Kanjaksha . Mohanty . Dipika . September 2002 . Defining the allelic variants of HLA A19 in the western Indian population . Human Immunology . en . 63 . 9 . 779–782 . 10.1016/S0198-8859(02)00424-X.
  32. Book: Sasazuki, Takehiko . Tsuji, Kimiyoshi . Aizawa, Miki . HLA 1991: proceedings of the eleventh International Histocompatibility Workshop and Conference, held in Yokohama, Japan, 6-13 November, 1991 . Oxford University Press . Oxford [Oxfordshire] . 1992 . 0-19-262390-7 .
  33. bears the C*0502 instead of the C*0802 otherwise seen with this haplotype
  34. Saito S, Ota S, Yamada E, Inoko H, Ota M . Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population . Tissue Antigens . 56 . 6 . 522–9 . 2000 . 11169242 . 10.1034/j.1399-0039.2000.560606.x . free .
  35. Williams F, Meenagh A, Darke C, etal . Analysis of the distribution of HLA-B alleles in populations from five continents . Hum. Immunol. . 62 . 6 . 645–50 . 2001 . 11390040 . 10.1016/S0198-8859(01)00247-6 .
  36. Ward FE, Jensen JB, Abdul Hadi NH, Stewart A, Vande Waa JV, Bayoumi RA . HLA genotypes and variant alleles in Sudanese families of Arab-Negroid tribal origin . Hum. Immunol. . 24 . 4 . 239–51 . 1989 . 2708086 . 10.1016/0198-8859(89)90018-9 .
  37. bears the A*3303:B*5802

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