Diego antigen system
The Diego antigen (or blood group) system is composed of 21 blood factors or antigens carried on the Band 3 glycoprotein, also known as Anion Exchanger 1 (AE1). The antigens are inherited through various alleles of the gene SLC4A1 (Solute carrier family 4), located on human chromosome 17. The AE1 glycoprotein is expressed only in red blood cells and, in a shortened form, in some cells in the kidney. The Diegoa antigen is fairly common in Indigenous peoples of the Americas (in both North and South America) and East Asians, but very rare or absent in most other populations, supporting the theory that the two groups share common ancestry.
The Diego system is named after a pair of types, Diegoa (Dia) and Diegob (Dib), which differ by one amino acid in the AE1 glycoprotein, corresponding to one difference in the nucleotide sequence of the SLC4A1 gene. Dib is common or ubiquitous in all populations which have been screened for it, while Dia has been found only in Indigenous peoples of the Americas (in both North and South America) and East Asians, and in people with some ancestors from those groups. People heterozygous for the two alleles produce both antigens. No individual has been tested who does not produce one, or both, of the two antigens. Anti-Dia (the antibody to Dia) can cause severe hemolytic disease of the newborn and severe transfusion reaction. Anti-Dib usually causes milder reactions.
The Wright blood system is another pair of types, Wrighta (Wra) and Wrightb (Wrb), also differing by one amino acid on the AE1 glycoprotein and one nucleotide on the SLC4A1 gene. Wra always expresses antigens, but the antibody reaction of Wrb depends on a variation in the structure of glycophorin A, which binds with Wrb. Anti-Wra can also cause severe hemolytic disease of the newborn and severe transfusion reaction. Anti-Wrb is very rare, and little data is available on its severity.
Seventeen other rare blood types (as of 2002) are included in the Diego antigen system, as they are produced by mutations on the SLC4A1 gene. These include the Waldner (Wda), Redelberger (Rba), Warrior (WARR), ELO, Wulfsberg (Wu), Bishop (Bpa), Moen (Moa), Hughes (Hua), van Vugt (Vga), Swann (Swa), Bowyer (BOW), NFLD, Nunhart (Jna), KREP, Traversu (Tra), Froese (Fra) and SW1 types.
The first Diego antigen, Dia, was discovered in 1953, when a child in Venezuela died of hemolytic disease three days after birth. Rh and ABO blood type mismatches were soon ruled out, and investigators began searching for a rare blood factor. Red blood cells from the father reacted strongly to blood serum from the mother. Rare blood types known at the time were eliminated, and the new type was classified as a "private" or "family" blood type. The investigators, with the agreement of the father, named the new type after his surname, "Diego". In 1955 investigators found that the Diego family included ancestry from Indigenous peoples of the Americas, and that the Diego factor (Dia) was not restricted to the Diego family, but occurred in several populations in Venezuela and elsewhere in South America. Investigators suspected that the Diego factor might be a Mongoloid trait, and tested groups of Native Americans in the United States and people of Chinese and Japanese ancestry, and found Dia in those groups. Anti-Dib was found in 1967, establishing the Diego group as a two-antigen system. In 1993 the Diego pair of antigens was found to result from a single point mutation (nucleotide 2561) on what is now called the SLC4A1 gene on chromosome 17.
The Wrighta antigen (Wra), a very low frequency blood type, was also discovered in 1953. The Wrightb antigen (Wrb), a very high frequency blood type, was discovered about a decade later, but the two types were not recognized as a pair for another 20 years. The Wright group was eventually identified as a single point mutation on the SLC4A1 gene. The Wright group was subsumed into the Diego group in 1995, since its location on the SLC4A1 gene had been determined after the Diego group had been located there.
Starting in 1995, various rare antigen types, some of which had been known for 30 years, were found to also be caused by mutations on the SLC4A1 gene, and were therefore added to the Diego system.
Distribution of the Diegoa antigen
The Dib antigen has been found in all populations tested. The Dia antigen, however, has been found only in populations of indigenous peoples of the Americas and East Asians, and people with some ancestry in those populations. Some groups in South America have a relatively high frequency of Dia+. A sample of the Kaingang people of Brazil was 49% Dia+. Samples of other groups in Brazil and Venezuela were 14% to 36% Dia+.
While the Dia antigen is found at moderate to high frequencies in most populations of indigenous peoples in South America, it is absent in the Waica people, and occurs at very low frequencies in the Warao and Yaruro people of interior northern South America. Layrisse and Wilbert, who characterize these people as "Marginal Indians", proposed that they are remnants of a first migration into South America of people who had not acquired the allele for the Dia antigen, with other indigenous peoples of South America resulting from a later migration.
Samples of groups in Guatemala and Mexico have 20% to 22% Dia+. Samples from Native American groups in the United States and First Nations groups in Canada have 4% to 11% Dia+. Although the incidence of Diegoa+ is relatively high in Siberian Eskimos and Aleut people (the incidence of Diegoa+ in Aleuts is comparable to South American levels), it occurs at a much lower frequency (less than 0.5%) among Alaskan Eskimos and has not been found in the Inuit of Canada. 
The Dia antigen is widespread in East Asian populations. Samples of East Asian populations show 4% Dia+ for the Ainu of Hokkaido, 2% to 10% Dia+ for Japanese, 6% to 15% Dia+ for Koreans, 7% to 13% Dia+ for Mongolians, 10% Dia+ for northern Chinese and 3% to 5% Dia+ for southern Chinese.
The Dia antigen is also found in northern India and in Malaysia, where there are populations of East Asian ancestry. North Indians (of unspecified ethnicity) are reported to be 4% Dia+. On the other hand, a sample of Indian students attending the University of Michigan, the majority of which were Gujarati, found none to be Dia+. A survey of residents of the Klang Valley in Malaysia found the incidence of Dia+ in ethnic Chinese to be 4%, in ethnic Malays to be a little over 1%, and in ethnic Indians (descended from southern Indians) to be a little under 1%. (A smaller sample of Malays in Penang, Malaysia, were 4% Dia+.)
The Dia antigen is very rare in African and European populations. One West African subject had an ambiguous possible reaction to Dia. About 0.5% of Europeans of Polish ancestry have been found to be Dia+. This incidence has been attributed to gene mixture from Tatars who invaded Poland five to seven centuries ago. The Dia antigen is very rare or absent in Aboriginal Australians, Papuans, natives of New Britain, and Polynesians.
- Junqueira, Pedro C.; Lilian Castilho (March 2002). "The history of the Diego blood group" (PDF). Revista Brasileira de Hematologia e Hemoterapia 24 (1): 15–23. doi:10.1590/s1516-84842002000100004. Retrieved 10 September 2013.
- Poole, J. (1999). "The Diego blood group system—an update" (PDF). Immunohematology 15 (4). Retrieved 10 September 2013.
- Huang, Cheng-Han; Marion E. Reid, Shen-S- Xie and Olga O. Blumenfeld (1996). "Human red blood cell Wright antigens: a genetic and evolutionary perspective on glycophorin A-band 3 interaction" (PDF). Blood 87: 3942–3947. Retrieved 10 September 2013.
- Schenkel-Brunner, H. (2000). Human Blood Groups. Wien: Springer-Verlag. pp. 527–528.
- Layrisse, M; Wilbert, J (1961). "Absence of the Diego antigen, a genetic characteristic of early immigrants to South America". Science 134 (3485): 1077–8. doi:10.1126/science.134.3485.1077. PMID 14463057.
- Gershowitz, Henry (1959). "The Diego Factor among Asiatic Indians, Apaches and West African Negroes; Blood Types of Asiatic Indians and Apaches". American Journal of Physical Anthropology 17 (3): 195–200. doi:10.1002/ajpa.1330170305. PMID 13827615. Retrieved 13 September 2013.
- Mourant, A. E. (1977). "The genetic markers of the blood". In Geoffrey Ainsworth Harrison. Population Structure and Human Variation. Cambridge: Cambridge University Press. p. 28. ISBN 0-521-21399-1. Retrieved 16 September 2013.
- Zlojutro, Mark (2008). Mitochondrial DNA and Y-chromosome Variation of Eastern Aleut Populations. University of Kansas. p. 59. Retrieved 16 September 2013.
- Chown, Bruce; Marion Lewis; Hiroko Kaita (25 January 1958). "The Diego Blood Group System". Nature 181: 268. doi:10.1038/181268a0. Retrieved 14 September 2013.
- Eriksson, A. W.; W. Lehmann; N. E. Simpson (1980). "Genetic Studies on circumpolar populations". In Frederick A. Milan. The Human Biology of Circumpolar Populations. Cambridge: Cambridge University Press. pp. 94, 114. ISBN 0-521-22213-3. Retrieved 14 September 2013.
- Wei, Cheong Tar; Faisal Muti Al-Hassan; Norris Naim; Aishah Knight; Sanmukh R Joshi (2013). "Prevalence of Diego blood group antigen and the antibody in three ethnic population groups in Klang valley of Malaysia". Asian Journal of Transfusion Science 7 (1): 26–28. doi:10.4103/0973-6247.106725. PMID 23559760. Retrieved 13 September 2013.