HLA-A68

HLA-A68

SerotypeA_normal
locus = A
type = 68



image_
PDB2|2hla showing A*6801 (cyan) and Beta-2 microglobulin (rose). There is no bound peptide in this image.
allelegroup = 68
alleles = 1
common_alleles = 3
rare_alleles = 1
alias = A28
broad = 28 | sister1 = 69
allele1 = 01
nick1 = Aw68.1
images1 = PDB2|2hla, PDB2|1tmc, PDB2|1hsb
cAllele2 = 02
cNick2 = Aw68.2
cAllele3 = 03
cNick3 = -
rallele1 = 05
rnick1 = -
lead_comment =
mode = North America
types = 3
2ndType = 28
3rdType = 69
type1alle1freq = 27 | type2alle1freq = 63 | N1 = 2736
type1alle1freq = 19 | type2alle1freq = 72 | type3alle1freq = 1| N2 = 2327
type1alle1freq = 28 | type2alle1freq = 63 | N3 = 202
type1alle1freq = 29 | type2alle1freq = 53 | N4 = 59
serotype_comment = is poor, with low specific detection, high non-specific identification by A28

Disease Associations

By allele

A*68 is associated with higher viral load in HIVcite journal | author = Tang J, Tang S, Lobashevsky E, Myracle A, Fideli U, Aldrovandi G, Allen S, Musonda R, Kaslow R | title = Favorable and unfavorable HLA class I alleles and haplotypes in Zambians predominantly infected with clade C human immunodeficiency virus type 1. | journal = J Virol | volume = 76 | issue = 16 | pages = 8276–84 | year = 2002 | pmid = 12134033 | doi = 10.1128/JVI.76.16.8276-8284.2002] cite journal | author = Gostick E, Cole DK, Hutchinson SL, "et al" | title = Functional and biophysical characterization of an HLA-A*6801-restricted HIV-specific T cell receptor | journal = Eur. J. Immunol. | volume = 37 | issue = 2 | pages = 479–86 | year = 2007 | pmid = 17273992 | doi = 10.1002/eji.200636243] . A68 may be protectiveagainst symptomatic heart disease in Chaga's cardiomyopathy.cite journal | author = Cruz-Robles D, Reyes PA, Monteón-Padilla VM, Ortiz-Muñiz AR, Vargas-Alarcón G | title = MHC class I and class II genes in Mexican patients with Chagas disease | journal = Hum. Immunol. | volume = 65 | issue = 1 | pages = 60–5 | year = 2004 | pmid = 14700597 | doi = ]

Allele freqeuncies

AlleleFreq
Placement = right
Allele = A*6801
Freq1 = 25.0 | People1 = Brazil Terena
Freq2 = 19.7 | People2 = Mexico Sonora Seri
Freq3 = 15.5 | People3 = USA Alaska Yupik Natives
Freq4 = 13.7 | People4 = Mexico Mixtec Oaxaca
Freq5 = 12.0 | People5 = India Khandesh Pawra
Freq6 = 11.2 | People6 = Mexico Zaptotec Oaxaca
Freq7 = 9.4 | People7 = Burkina Faso Mossi
Freq8 = 9.1 | People8 = Mexico Chihuahua State Ta…
Freq9 = 9.0 | People9 = Ecuador Cayapa
Freq10 = 8.0 | People10 = South Africa Natal Tamil
Freq11 = 7.7 | People11 = Pakistan Sindhi
Freq12 = 7.5 | People12 = India Mumbai Marathas
Freq13 = 7.5 | People13 = Pakistan Kalash
Freq14 = 7.4 | People14 = India Tamil Nadu Nadar
Freq15 = 7.0 | People15 = Senegal Niokholo Mandenka
Freq16 = 6.7 | People16 = Georgia Tibilisi Kurds
Freq17 = 6.3 | People17 = Georgia Svaneti Svans
Freq18 = 6.1 | People18 = Mexico Mestizos
Freq19 = 6.0 | People19 = India West Bhils
Freq20 = 6.0 | People20 = Portugal Centre
Freq21 = 5.7 | People21 = Belguim
Freq22 = 5.6 | People22 = Mexico Mixe Oaxaca
Freq23 = 5.6 | People23 = Saudi Arabia Guraiat and …
Freq24 = 5.6 | People24 = USA North American Native…
Freq25 = 5.2 | People25 = USA South Texas Hispanics
Freq26 = 5.0 | People26 = Cameroon Pygmy Baka
Freq27 = 4.8 | People27 = Cape Verde Northwestern I…
Freq28 = 4.8 | People28 = Georgia Tibilisi Georgian…
Freq29 = 4.7 | People29 = Croatia
Freq30 = 4.5 | People30 = Finland
Freq31 = 4.4 | People31 = Scotland Orkney
Freq32 = 4.3 | People32 = Oman
Freq33 = 4.2 | People33 = Morocco 'berber' Nador Me…
Freq34 = 4.1 | People34 = Australia New South Wales
Freq35 = 4.0 | People35 = USA African America
Freq36 = 3.9 | People36 = China Inner Mongolia
Freq37 = 3.9 | People37 = Guadalajara Mestizos (2)
Freq38 = 3.8 | People38 = Cameroon Sawa
Freq39 = 3.6 | People39 = Mali Bandiagara
Freq40 = 3.5 | People40 = Tunisia
Freq41 = 3.4 | People41 = India Andhra Pradesh Goll…
Freq42 = 3.4 | People42 = Ireland South
Freq43 = 3.2 | People43 = Cameroon Beti
Freq44 = 3.2 | People44 = Pakistan Baloch
Freq45 = 3.1 | People45 = Burkina Faso Fulani
Freq46 = 3.0 | People46 = India West Coast Parsis
Freq47 = 3.0 | People47 = Israel Arab Druse
Freq48 = 3.0 | People48 = Japan Ainu Hokkaido
Freq49 = 3.0 | People49 = South Africian Natal Zulu
Freq50 = 3.0 | People50 = Sudanese
Freq51 = 3.0 | People51 = USA Caucasian
Freq52 = 2.9 | People52 = India North Hindus
Freq53 = 2.9 | People53 = Pakistan Brahui
Freq54 = 2.8 | People54 = Uganda Kampala
Freq55 = 2.7 | People55 = Iran Baloch
Freq56 = 2.7 | People56 = Ireland Northern
Freq57 = 2.6 | People57 = Romanian
Freq58 = 2.6 | People58 = USA Hispanic
Freq59 = 2.5 | People59 = Brazil
Freq60 = 2.4 | People60 = France South East
Freq61 = 2.3 | People61 = Guinea Bissau
Freq62 = 2.3 | People62 = Spain Catalonia Girona
Freq63 = 2.2 | People63 = China Beijing
Freq64 = 2.0 | People64 = France Corsica
Freq65 = 2.0 | People65 = Singapore Javanese Indone…
Freq66 = 2.0 | People66 = USA South Dakota Lakota S…
Freq67 = 1.8 | People67 = Bulgaria
Freq68 = 1.7 | People68 = Mongolia Buriat
Freq69 = 1.7 | People69 = USA Arizona Pima
Freq70 = 1.5 | People70 = Spain Eastern Andalusia
Freq71 = 1.4 | People71 = Kenya
Freq72 = 1.3 | People72 = Cameroon Bamileke
Freq73 = 1.3 | People73 = Zimbabwe Harare Shona
Freq74 = 1.1 | People74 = Russia Tuva (2)

A68 can be subdivided into 3 alleles, *6801, *6802, *6803. *6801 can also be subdivided into *680101 and *680102 (previously called *68011 and *68012).

A*6801

A*6801 is higher in certain Native American groups, South Asian peoples, African peoples, however *6801 is at low levels in most of SE Asia, particularly the indigeonous populations. This is also reflected by low levels along the West Pacific Rim including Japan. The hiatus of *6801 breaks in Northern Japan with the 3% frequency found in the Ainu, which continues to increase with Arctic peoples and falls of in Native Americans. Whereas in the Western Eurasia's northern regions, A*6801 falls off. In both Africa and the New World both A*680101 and A*680102 can be found.cite journal | author = Middleton D, Menchaca L, Rood H, Komerofsky R | title = New allele frequency database: http://www.allelefrequencies.net | journal = Tissue Antigens | volume = 61 | issue = 5 | pages = 403–7 | year = 2003 | pmid = 12753660 | doi = ] Although in the New World A*680102 is more prevalent.

A*6802

A*6802 has a global node within certain native peoples of South America, at 37%. A secondary node can be found in Africa. Like *6801 there is an hiatus of *6802 in SE Asia's indigeonous populations, indicating that this population is not a likely source within the native peoples of the New World. Levels are generally low (<1%) in Europe except along the Mediterranean coast. In Africa, higher levels can be found in Kenya and in Western Africa and the Cape Verde Islands. A note on purity, the notion that A*6802 is of indigeonous native American origin can be challenged based on possibility of introgression from Europeans and Africans. In the case of the Yucpa this is not teneble. The Yucpa have an HLA-DQ8 frequency of ~80%, the highest DQ allele frequency in the world, this tribe shows little evidence of European genetic introgression, in addition the closest DQ8 frequency in terms of Africa are the isolated !Kung of Namibia. There are two possible sources of A*6802: Africa direct and Africa via Asia. The associated B alleles (B*48, B*61) point toward and Asian origin or an African source of very ancient origin, since time would be required to recombine Asian typical B alleles with A68. In the Spanish, A28 levels are 3.1% of this ~0.5% is A*6901, A*6802 is about 2.0% which means the net level of A*6802 to A*6805 in the Spanish is ~0.5%. Of 11 NA groups surveyed 9 are above and 2 are below 0.5%. Of the two Spanish groups 1 (Andalusia - 1.5%) is above and the other (Catalon 0.0%) is below. In an admixture modelSpanish introgression does not explain A*6802 in the New World. The Asian model of migration shows no single people NE of Pakistan that has A*6802.

A*6803

A*6803 can be found in native peoples of the New World and in Central Asia, in Africa it appears to be limited to West and Central Africans. This distribution along with the information on 6801 and 6802 suggests a probable redistribution of *68 alleles from Africa after the initial migration from East Africa that colonized Southeast Asia. It also provides support for 2 waves of migration from Asia to the New World or, at minimum, an unknown mixing area of West Pacific Rim haplotypes and West African/Middle Eastern derived haplotypes in Eastern Asia before the first migration. At present the incursion of Western Eurasian peoples into East Asia follows evidence for reuse of transbiakal region after 18,300 years and correlates with the insipient Jomon period of Japan several thousands of years later. Certain alleles and haplotypes of HLA in South Americans target Japans estimated pre-Yayoi composition, but other peoples, for example in western Mexico are most similar to the Ainu and the peoples of the Amur basin.

A*6805

A*6805 is found in the Guatemalan and Central African Mbenzele at low levels.

A68 haplotypes

The genetic distance between Native Americans and Eurasians is too great for the persistence of shared haplotypes, particularly in light of the lower levels in most of Siberia. The link of haplotypes with Western Africa may be significant, and may indicate a rapid eastward migration and admixing within the late paleolithic period.

Indigeonous American haplotypes

A*680102-B35 haplotypes
* A*680102 Cw*0304 B*3506 (A68-Cw10-B35)
* A68-Cw4-B35 (Terena, Seri (Mexico))
** A*680102 Cw*0401 B83521 (A68-Cw4-B35) (Terena)

A*6802-B35
* A*6802-B3501 Guadalahara.
* A*6802-B3502 Guadalahara.

A68-B35 Mayan (A*6803).

These two haplotypes are consistent with the presence of Cw4-B35 and A68 in Asia and Middle East and A68-B35 maybe the ancestral A68 haplotype. A28(A*6802)-B35 is found in Senegal. [Note: Since freq(A28) = freq(A68) + freq(A69) and A69 is not widely distributed in Africa (mainly levant, cape verde islands, certain tribes in Burkino Faso), A28 frequencies can generally be treated as A68 frequencies] ]

A6801-B4002/4 - Terena, Eskimo, Mestizo, Tribal Indians (Asia)

A*680102-B*520102 in the Mexican Mestizo population. A28(A*6802)-B52 is also found in Senegal.

Old World A68 haplotypes

A28(~A68)-B51 Armenia, Senegal, Eskimo
A28(~A68)-B70 W. Afr, Zaire, Zimbabwe, N. and S. African (Non-caucasians), Khoi (Hottentot)

References


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