HLA-B46

Last updated November 09, 2023




major histocompatibility complex (human), class I, B46
Alleles	B*4601
Structure (See HLA-B)
Symbol(s)	HLA-B
EBI-HLA	B*4601
Locus	chr.6 6p21.31

HLA-B46 (B46) is an HLA-B serotype. The serotype identifies the gene products of HLA-B*4601 allele.^[1] B*4601 resulted from a rare, interlocus, gene conversion between B62, probably B*1501, and a HLA-C allele.^[2] B*4601 is the most common HLA-B allele that does not have an origin within Africa, and estimated 400 million people in Eastern Asia carry a B46 allele. When found B*4601 segregates with only 2 HLA-Cw alleles, A limited number of HLA-A and HLA-DRB1 alleles suggesting that the allele recently expanded from a limited sized group within SE Asia. Extremely low frequencies outside of Eastern Asia are indicators of a recent expansion of B46 from a recently small population. The frequency distribution suggests the ancestral B46 population was in SE China, or, potentially Burma (Myanmar or Laos, untested). B46 in Asia correlates with wet-rice farming. The exceptions are notable, it has been found in the Nivkhi on north-eastern Sakalin Island, the Ainu, and the Nivkhi-related (genetically) Tlinglet population of Alaska at trace levels.

Serotype

B46 serotype recognition of Some HLA B*46 allele-group gene products^[3]
B*46	B46	Other	Sample
allele	%	%	size (N)
4601	59	29	1487

The serotyping is poor for B*4601 and it is preferable to use SSP-PCR. B*46:01 is one of the four B alleles that reacts with neither Bw4 nor Bw6. The others are B*18:06, B*55:03 and B*73:01.^[4]

B*4601 Allele Frequencies

**HLA B*4601 frequencies**
		freq
ref.	Population	(%)
^[5]	Buyei (China)	21.6
^[5]	Miao (China)	18.4
^[6]	Han (2) (Yunnan, China)	17.9
^[6]	Thai (in Singapore)	17.2
^[6]	Southern Chinese (in Taiwan)	17.2
^[6]	Chinese (in Hong Kong)	16.3
^[6]	Hakka (2)(Taiwan)	15.6
^[6]	Guangzhou (China)	15.5
^[6]	Northeastern Thailand	15.1
^[6]	Minnan (Avg 1 & 2) (Taiwan)	15.0
^[6]	Middle' Chinese (in Taiwan)	15.0
^[6]	Hakka (Taiwan)	13.6
^[6]	Wuhan (China)	13.5
^[6]	Maonan (Guangxi, China)	13.4
^[6]	Chinese (in Singapore)	13.4
^[5]	Vietnamese	13.2
^[6]	Southern Han (China)	11.5
^[6]	Shanghai (China)	11.2
^[6]	Meizhou Han (Guangdong, China)	10.0
^[6]	Shijiazhuang Tianjian Han (Beijing)	9.6
^[6]	Guangzhou Han (China)	9.4
^[6]	Thailand	9.2
^[6]	Nu (Yunnan, China)	9.0
^[6]	Northern Chinese (in Taiwan)	8.6
^[6]	Pazeh (Taiwan)	8.2
^[6]	Aichi (Japan)	7.6
^[6]	Lisu (Yunnan, China)	7.2
^[6]	Beijing (China)	6.8
^[6]	Naxi (Yunnan, China)	6.1
^[6]	Hui (Qinghai, China)	5.9
^[6]	Northern Han (China)	5.7
^[6]	Japan (3)	5.0
^[6]	Hyogo (Japan)	4.7
^[6]	South Korea (3)	4.4
^[6]	Man (Harbin City, China)	4.1
^[6]	Siraya (Taiwan)	3.9
^[6]	Central Japan	3.6
^[6]	Linqu County (Shandong, China)	3.3
^[6]	Timorese	2.6
^[6]	Inner Mongolia (China)	2.0
^[6]	Javanese (in Singapore)	2.0
^[6]	Oold (Mongolia)	1.9
^[6]	Nivkhi (Sakhalin I, Russia) sland	1.9
^[6]	Thao (Taiwan)	1.7
^[6]	Riau Malay (in Singapore)	1.5
^[6]	Tuva (2) (Russia)	1.4
^[6]	Tibetan (China)	1.3
^[6]	Khalkh (Ulaanbaatar, Mongolia)	1.2
^[6]	Ainu (Hokkaidō, Japan)	1.0
^[6]	Okinawa (in Hawaii, USA)	1.0
^[6]	Indigenous (Taiwan)	0.9
^[6]	Khalkha (Mongolia)	0.5
^[6]	Brahui (Pakistan)	0.5

A2-Cw11(1)-B46

This haplotype is unique in several regards, first and most importantly the B46 serotype is not from Africa, this distinguishes 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 wherever Asian wet-rice farming peoples have traveled and is found at low frequencies in non-farming indigenous 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 indigenous populations of most peoples in the world.

HLA A2-B46 haplotype frequencies
		freq		Rank in
ref.	Population	(%)		Pop.
^[5]	Buyi	16.6	¹	1
^[5]	Miao	13.6		1
^[5]	Singapore (Chinese)	11.4		2
^[7]	Chaoshan	10.1		1
^[5]	Southern Han	7.8		2
^[5]	VietNam	7.8		1
^[5]	Thai	7.2		1
^[5]	Thai Chinese	4.0
^[5]	Japanese	3.3		4
^[5]	Li	3.0
^[5]	Korea	2.8
^[5]	Uygar	2.7
^[5]	Manchu	2.6
^[5]	Inner Mong.	1.9
^[5]	Northern Han	1.8
¹ highest freq. A-B hap in Asia.

This haplotype is unique in several regards, first and most importantly the B46 serotype is not from Africa, this distinguishes it from every other major B serotype except B*48. 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 wherever Asian wet-rice farming peoples have traveled and is found at low frequencies in non-farming indigenous 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 indigenous 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.

Related Research Articles

The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

HLA DR3-DQ2 is double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype. Certain HLA DR and DQ genes have known involvement in autoimmune diseases. DR3-DQ2, a multigene haplotype, stands out in prominence because it is a factor in several prominent diseases, namely coeliac disease and juvenile diabetes. In coeliac disease, the DR3-DQ2 haplotype is associated with highest risk for disease in first degree relatives, highest risk is conferred by DQA1*0501:DQB1*0201 homozygotes and semihomozygotes of DQ2, and represents the overwhelming majority of risk. HLA DR3-DQ2 encodes DQ2.5cis isoform of HLA-DQ, this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. The DQ2.5 isoform, however, is many times more frequently associated with autoimmune disease, and as a result to contribution of DQ2.2 is often ignored.

<span class="mw-page-title-main">HLA-DQ2</span>

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β² subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">HLA-DQ4</span>

HLA-DQ4 (DQ4) is a serotype subgroup within HLA-DQ(DQ) serotypes. The serotype is determined by the antibody recognition of β⁴ subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ4 are encoded by the HLA-DQB1*04 allele group. This group currently contains 2 common alleles, DQB1*0401 and DQB1*0402. HLA-DQ4 and HLA-DQB1*04 are almost synonymous in meaning. DQ4 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ4.3 and DQ4.4, are also encoded by the DQA1*0303 and DQA1*0401 genes, respectively.

<span class="mw-page-title-main">HLA-DQ6</span>

HLA-DQ6 (DQ6) is a human leukocyte antigen serotype within HLA-DQ (DQ) serotype group. The serotype is determined by the antibody recognition of β⁶ subset of DQ β-chains. The β-chain of DQ isoforms are encoded by HLA-DQB1 locus and DQ6 are encoded by the HLA-DQB1*06 allele group. This group currently contains many common alleles, DQB1*0602 is the most common. HLA-DQ6 and DQB1*06 are almost synonymous in meaning. DQ6 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 α-chains. There are many haplotypes of DQ6.

<span class="mw-page-title-main">HLA-DQ7</span>

HLA-DQ7 (DQ7) is an HLA-DQ serotype that recognizes the common HLA DQB1*0301 and the less common HLA DQB1*0304 gene products. DQ7 is a form of 'split antigen' of the broad antigen group DQ3 which also contains DQ8 and DQ9.

<span class="mw-page-title-main">HLA-DQ1</span> Serotype that covers a broad range of HLA-DQ haplotypes.

HLA-DQ1 is a serotype that covers a broad range of HLA-DQ haplotypes. Historically it was identified as a DR-like alpha chain called DC1; later, it was among 3 types DQw1, DQw2 and DQw3. Of these three serotyping specificities only DQw1 recognized DQ alpha chain. The serotype is positive in individuals who bear the DQA1*01 alleles. The most frequently found within this group are: DQA1*0101, *0102, *0103, and *0104. In the illustration on the right, DQ1 serotyping antibodies recognizes the DQ α (magenta), where antibodies to DQA1* gene products bind variable regions close to the peptide binding pocket.

<span class="mw-page-title-main">HLA-DR17</span>

HLA-DR17 (DR17) is an HLA-DR serotype that recognizes the DRB1*0301 and *0304 gene products. DR17 is found at high frequency in Western Europe. DR17 is part of the broader antigen group HLA-DR3 and is very similar to the group HLA-DR18.

<span class="mw-page-title-main">HLA-DR16</span>

HLA-DR16(DR16) is a HLA-DR serotype that recognizes the DRB1*1601, *1602 and *1604 gene products. DR16 is found in the Mediterranean at modest frequencies. DR16 is part of the older HLA-DR2 serotype group which also contains the similar HLA-DR15 antigens.

<span class="mw-page-title-main">HLA-DR15</span>

HLA-DR15 (DR15) is a HLA-DR serotype that recognizes the DRB1*1501 to *1505 and *1507 gene products. DR15 is found at high levels from Ireland to Central Asia. DR15 is part of the older HLA-DR2 serotype group which also contains the similar HLA-DR16 antigens.

<span class="mw-page-title-main">HLA-DR7</span>

HLA-DR7 (DR7) is a HLA-DR serotype that recognizes the DRB1*0701 to *0705 gene products.

<span class="mw-page-title-main">HLA-DR3</span>

HLA-DR3 is composed of the HLA-DR17 and HLA-DR18 split 'antigens' serotypes. DR3 is a component gene-allele of the AH8.1 haplotype in Northern and Western Europeans. Genes between B8 and DR3 on this haplotype are frequently associated with autoimmune disease. Type 1 diabetes mellitus is associated with HLA-DR3 or HLA-DR4. Nearly half the US population has either DR3 or DR4, yet only a small percentage of these individuals will develop type 1 diabetes.

<span class="mw-page-title-main">HLA-A*02</span>

HLA-A*02 (A*02) is a human leukocyte antigen serotype within the HLA-A serotype group. The serotype is determined by the antibody recognition of the α2 domain of the HLA-A α-chain. For A*02, the α chain is encoded by the HLA-A*02 gene and the β chain is encoded by the B2M locus. In 2010 the World Health Organization Naming Committee for Factors of the HLA System revised the nomenclature for HLAs. Before this revision, HLA-A*02 was also referred to as HLA-A2, HLA-A02, and HLA-A*2.

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. 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.

HLA-Cw*16 (Cw*16) is an HLA-C allele-group. The serotype identifies the more common HLA-Cw*16 gene products. This allele group is most commonly found in West Africa, but A single Haplotype of Cw16 is found in Western Europe at unusually high frequencies. There is no useful serology for Cw*16.

HLA-B53 (B53) is an HLA-B serotype. The serotype identifies the more common HLA-B*53 gene products. The B53 sequence is identical to B35 but short sequence specifies a Bw4 rather than a Bw6 motif, indicating B53 is a recent product of gene conversion. This suggests an origin for HLA-B53 involving a gene conversion of HLA-B35 by an allele containing this Bw4 sequence.

<span class="mw-page-title-main">HLA-B7</span>

HLA-B7 (B7) is an HLA-B serotype. The serotype identifies the more common HLA-B*07 gene products. B7, previously HL-A7, was one of the first 'HL-A' antigens recognized, largely because of the frequency of B*0702 in Northern and Western Europe and the United States. B7 is found in two major haplotypes in Europe, where it reaches peak frequency in Ireland. One haplotype A3-B7-DR15-DQ1 can be found over a vast region and is in apparent selective disequilibrium. B7 is a risk factor for cervical cancer, sarcoidosis, and early-onset spondylarthropathies.

HLA-B55 (B55) is an HLA-B serotype. B55 is a split antigen from the B22 broad antigen, sister serotypes are B54 and B56. The serotype identifies the more common HLA-B*55 gene products.

<span class="mw-page-title-main">HLA-B45</span>

HLA-B45 (B45) is an HLA-B serotype. The serotype identifies the B*45 gene-allele protein products of HLA-B.

HLA B7-DR15-DQ6 is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles, common multigene haplotypes are generally the result of descent by common ancestry. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

References

↑ Marsh, S. G.; Albert, E. D.; Bodmer, W. F.; Bontrop, R. E.; Dupont, B.; Erlich, H. A.; Fernández-Viña, M.; Geraghty, D. E.; Holdsworth, R.; Hurley, C. K.; Lau, M.; Lee, K. W.; Mach, B.; Maiers, M.; Mayr, W. R.; Müller, C. R.; Parham, P.; Petersdorf, E. W.; Sasazuki, T.; Strominger, J. L.; Svejgaard, A.; Terasaki, P. I.; Tiercy, J. M.; Trowsdale, J. (2010). "Nomenclature for factors of the HLA system, 2010". Tissue Antigens. 75 (4): 291–455. doi:10.1111/j.1399-0039.2010.01466.x. PMC 2848993 . PMID 20356336.
↑ Hildebrand WH, Domena JD, Shen SY, et al. (1994). "HLA-B15: a widespread and diverse family of HLA-B alleles". Tissue Antigens. 43 (4): 209–18. doi:10.1111/j.1399-0039.1994.tb02327.x. PMID 7521976.
↑ Allele Query Form IMGT/HLA – European Bioinformatics Institute
↑ Voorter, CE; van der Vlies, S; Kik, M; van den Berg-Loonen, EM (October 2000). "Unexpected Bw4 and Bw6 reactivity patterns in new alleles". Tissue Antigens. 56 (4): 363–70. doi:10.1034/j.1399-0039.2000.560409.x. PMID 11098937.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 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 978-0-19-262390-4.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens. 61 (5): 403–7. doi: 10.1034/j.1399-0039.2003.00062.x . PMID 12753660.{{cite journal}}: External link in |title= (help)
↑ 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. doi:10.1002/ajpa.20460. PMID 16883565.

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[pmid15787720-1] Marsh, S. G.; Albert, E. D.; Bodmer, W. F.; Bontrop, R. E.; Dupont, B.; Erlich, H. A.; Fernández-Viña, M.; Geraghty, D. E.; Holdsworth, R.; Hurley, C. K.; Lau, M.; Lee, K. W.; Mach, B.; Maiers, M.; Mayr, W. R.; Müller, C. R.; Parham, P.; Petersdorf, E. W.; Sasazuki, T.; Strominger, J. L.; Svejgaard, A.; Terasaki, P. I.; Tiercy, J. M.; Trowsdale, J. (2010). "Nomenclature for factors of the HLA system, 2010". Tissue Antigens. 75 (4): 291–455. doi:10.1111/j.1399-0039.2010.01466.x. PMC 2848993 . PMID 20356336.

[pmid7521976-2] Hildebrand WH, Domena JD, Shen SY, et al. (1994). "HLA-B15: a widespread and diverse family of HLA-B alleles". Tissue Antigens. 43 (4): 209–18. doi:10.1111/j.1399-0039.1994.tb02327.x. PMID 7521976.

[3] Allele Query Form IMGT/HLA – European Bioinformatics Institute

[4] Voorter, CE; van der Vlies, S; Kik, M; van den Berg-Loonen, EM (October 2000). "Unexpected Bw4 and Bw6 reactivity patterns in new alleles". Tissue Antigens. 56 (4): 363–70. doi:10.1034/j.1399-0039.2000.560409.x. PMID 11098937.

[isbn0-19-262390-7-5] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 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 978-0-19-262390-4.

[pmid12753660-6] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens. 61 (5): 403–7. doi: 10.1034/j.1399-0039.2003.00062.x . PMID 12753660.{{cite journal}}: External link in |title= (help)

[pmid16883565-7] 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. doi:10.1002/ajpa.20460. PMID 16883565.

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