HLA-A33

A33 frequencies

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 A3301-Cw0802-B1402 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 (B1401) and B65 (B*1402).

A*3303 distribution

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%). These frequencies increase in studies of populations from Western India, such as Maharashtra.

A33 haplotypes

A33-Cw8-B14-DR1-DQ5

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

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

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. This haplotype carries the other common DQ2 haplotype, DQ2.2. The Cw0701 is found in the A33-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

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 A3303, B5801, DRB11302, and DQB10609. 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.

References

References

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33. bears the C0502 instead of the C0802 otherwise seen with this haplotype
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36. (1989). "HLA genotypes and variant alleles in Sudanese families of Arab-Negroid tribal origin". Hum. Immunol..
37. bears the A3303:B'''5802'''