HLA-A33

HLA-A33 (A33) is a human leukocyte antigen serotype within HLA-A serotype group. The serotype is determined by the antibody recognition of α33 subset of HLA-A α-chains. For A33, the alpha "A" chain are encoded by the HLA-A*33 allele group and the β-chain are encoded by B2M locus.[1] A33 and A*33 are almost synonymous in meaning. A33 is a split antigen of the broad antigen serotype A19. A33 is a sister serotype of A29, A30, A31, A32, and A74.

Further information: History and naming of human leukocyte antigens
HLA-A33
(MHC Class I, A cell surface antigen)
HLA-A33
About
Proteintransmembrane receptor/ligand
Structureαβ heterodimer
SubunitsHLA-A*33--, β2-microglobulin
Subtypes
Subtype
allele
Available structures
A33 *3301
A33.3 *3303
{{{cNick3}}} *33{{{cAllele3}}}
{{{cNick4}}} *33{{{cAllele4}}}
Alleles link-out to IMGT/HLA database at EBI

A33 is more common in Subsaharan Africa.

Serotype
A33 recognition of some HLA A*33 gene products[2]
A*33 A33 A19 Sample
allele%% size (N)
*3301873687
*3303950807

A33 has a poor serotyping rate.

A33 frequencies
HLA A*3301 frequencies
freq
ref.Population(%)
[3]Pakistan Karachi Parsi12.2
[4]Portugal North7.6
[5]Tunisia6.1
[6]Morocco Nador Metalsa5.5
[4]Mongolia Buriat4.6
[7]Guinea Bissau4.6
[8]Jordan Amman3.5
[7]Cape Verde NW Islands3.2
[4]Portugal Centre3.0
[9]Iran Baloch2.8
[10]Pakistan Baloch2.4
[4]France South East2.3
[4]Sudanese1.8
[4]Japan Okinawa Ryukyuan1.8
[11]Mali Bandiagara1.8
[12]Bulgaria1.8
[10]Pakistan Kalash1.7
[11]Uganda Kampala1.5
[13]Georgia Svaneti1.3
[11]Kenya Luo1.3
[14]Oman1.3
[11]Zambia Lusaka1.2
[15]China Guangdong Meizhou1.0
[4]Romanian1.0
[4]Croatia1.0
[16]China Qinghai Hui0.9
[4]Czech Republic[17]0.9
[4]Kenya0.7
[18]Ireland Northern0.7
[14]Singapore Chinese0.6
[19]Cameroon Bamileke0.6
[20]India North Delhi0.5
[4]Georgia Tibilisi0.5
[4]Belgium0.5
[19]Cameroon Beti0.3
[11]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) but the only Arabian people which show both antigens are the United Arab Emirates.

A*3303 distribution
HLA A*3303 frequencies
freq
ref.Population(%)
[19]Cameroon Baka25.0
[19]Cameroon Sawa23.1
[4]India West Bhils18.0
[10]Pakistan Burusho17.9
[21]South Korea (3)16.3
[4]India West Parsis14.0
[4]Singapore Thai13.3
[4]India Mumbai Marathas13.0
[22]Japan12.8
[10]Pakistan Baloch12.7
[4]China South Han11.5
[4]Singapore Riau Malay10.9
[14]Singapore Chinese10.1
[4]Hong Kong Chinese10.0
[23] Chaoshan9.8
[11]Mali Bandiagara9.4
[16]China Inner Mongolia9.3
[4]Singapore Chinese Han9.3
[4]Singapore Javan9.0
[24]India North Hindus8.7
[7]Guinea Bissau8.5
[4]Taiwan Minnan8.3
[4]Taiwan Hakka8.2
[25]Senegal Mandenka8.1
[10]Pakistan Brahui8.0
[10]Pakistan Sindhi7.6
[4]Russia Tuvan7.1
[10]Pakistan Pathan7.1
[4]South Africa Natal Tamil7.0
[3]Pakistan Karachi Parsi6.7
[26]India Tamil Nadu Nadar6.6
[4]Israel Jews6.4
[4]India Andhra Pradesh Golla6.3
[27]China North Han6.2
[28]China Beijing Tianjian6.2
[20]India New Delhi6.1
[10]Pakistan Kalash5.8
[9]Iran Baloch5.6
[16]China Qinghai Hui5.5
[4]China Guangzhou5.4
[19]Cameroon Bamileke4.5
[29]China Yunnan Nu4.4
[4]China Guangxi Maonan4.2
[15]China Guangdong Meizhou4.0
[7]Cape Verde SW Islands4.0
[4]Taiwan Pazeh3.6
[4]Uganda Kampala3.1
[4]China Beijing3.0
[4]India Khandesh Pawra3.0
[19]Cameroon Yaounde2.8
[4]Sudanese2.5
[4]Zimbabwe Harare Shona2.4
[7]Cape Verde NW Islands2.4
[19]Cameroon Beti2.3
[14]Oman2.1
[30]China Tibet1.6
[4]Croatia1.3
[4]Romanian1.2
[29]China Yunnan Lisu1.1
[4]Arab Druse1.0
[4]Georgia Tibilisi1.0
[4]Belgium1.0
[11]Kenya Luo0.9
[31]Lakota Sioux0.5
[4]Australian Indig. Cape York0.5
[5]Tunisia0.5
[14]South African Natal Zulu0.5
[4]Kenya0.3
[18]Ireland Northern0.3
[11]Kenya Nandi0.2

Certain alleles confound population histories. At the top of that list is A*3303. This allele appears to jump, figuratively, out of West Africa into South Asia. The point of origin is Africa, most likely central or western Africa given the low levels in East Africa (although much of East Africa is undersampled). In certain tested populations of the Middle East the leve of A*3303 is either very low, or non-existent. Within East Africa Sudan appears to be the highest at around 2%. The frequency of A*3303 begins to rise in eastern Arabia (Oman, UAE) and then markedly rise in the Brahui and Balochi of Pakistan. One haplotype stands out, the A33-B58-DR3-DQ2 haplotype which is found in West Africa, in Sudan, and Pakistan, scattered along West Indias coast, the Turkic republics and appears to have recently introgressed into Korea (post-Yayoi period of Japan) and China. So recent arrival into Asia that the level of HLA DR3-DQ2 in Korea of 2.9%. Korea is the major recent source of Japanese genes, by the Yayoi period that lasted from 3000 to 1600 years ago approximately 3/4ths of Japanese genetic makeup is attributed to this migration. And yet there is trace DR3-DQ2 in Japanese, none in the Ainu nor many other indigeonous Siberian groups.

A33 Haplotypes

A33-Cw8-B14-DR1-DQ5
HLA A*33-B14 frequencies
freq
ref.Population(%)
[3]Parsis (Pakistan)4.4
[32]Sardinian3.0
India West Coast Parsis3.3 [33]
[32]Portuguese2.7
[32]Armenian2.5
[32]Indian2.0
[32]Polish2.0
Ashkenazi Jews1.8
[32]French1.8
[32]Panish1.7
[32]Albanian1.5
[32]German1.5
[32]Tuscan1.3
[32]Greek1.1
[32]Marathans1.1
[32]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 like 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*3301 : C*0802 : B*1402 : DRB1*0102 : DQA1*0102 : DQB1*0501

A33-B44
HLA A*33-B44 frequencies[32]
freq
ref.Population(%)
Iyers9.6
Korea8.0
Japan6.1
Thais4.7
[3]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, its a good reason why serotyping alone should not be relied upon. The first haplotype is A33-Cw14-B44-DR13-DQ6.4[34]

A*3303 : C*1403 : B*4403 : DRB1*1302 : DQA1*0102 : DQB1*0604 : DPB1*0401

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*3303 : C*0701 : B*4403 : DRB1*0701 : DQA1*0201? : DQB1*0202

The second haplotype, like A33-B58 is found in Korea but not in Japan.[21] This haplotype carries 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 resolution multigene haplotype studies.

A33-Cw3-B58-DR3-DQ2
HLA A*33-B58 frequencies
freq
ref.Population(%)
[32]Chinese (Thailand)12.6
[10]Baloch (Pakistan)11.1
[23]Chaoshan (China)8.1
[32]Chinese (Singapore)5.5
[10]Burusho (Pakistan)4.6
[32]Hui4.0
[32]Mongolian3.7
[10]Kalash (Pakistan)3.6
[32]Korea3.5
[32]Yaku3.2
[10]Panthan (Pakistan)3.0
[32]Tribals (India)3.0
Baloch (SE Iran)2.9
[10]Brahui (Pakistan)2.9
[32]Southern Han2.8
[32]Thais2.5
[32]Vietnamese2.3
[32]Inner Mongolian2.2
[32]Miao2.1
[32]West African2.1
[32]South African1.9
[35]Oman1.6
[10]Sindhi (Pakistan)1.5
[32]Manchu1.2
[36]Sudan1.2
Cameroon Yaounde[37]1.1

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

A*3303 : C*0302 : B*5801 : DRB1*0301 : DQA1*0501 : DQB1*0201

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 dissiquilbrium with on haplotype in particular, the specific genetic makeup is:

A*3303 : C*0701 : B*5801 : DRB1*1302 : DQA1*0102 : DQB1*0609

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.

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  33. bears the C*0502 instead of the C*0802 otherwise seen with this haplotype
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  37. bears the A*3303:B*5802

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