Molecular Biology Reports

, Volume 40, Issue 10, pp 5523–5530 | Cite as

HLA in Georgians (Caucasus) and their relationship with Eastern Mediterraneans

  • Diego Rey
  • Cristina Areces
  • Javier Alonso-Rubio
  • Mercedes Enríquez-de-Salamanca
  • Sedeka Abd-El-Fatah-Khalil
  • Nina Bendikuze
  • Mercedes Fernández-Honrado
  • Luz Barbolla
  • José Manuel Martín-Villa
  • Antonio Arnaiz-VillenaEmail author


HLA-A, -B, -DQB1, and –DRB1 typing has been performed in a sample of Georgian population (South Caucasus). Allele frequencies, neighbour joining and correspondence relatedness analyses and extended HLA haplotypes have been obtained with comparison with other Middle East and Mediterranean populations. Our Georgian sample tends to be genetically related in these analyses with Eastern Mediterraneans and Middle East people. This is important for future regional transplant programs, and Georgian HLA and disease epidemiology and pharmacogenomics.


Caucasians Georgians Greeks HLA Pharmacogenomics Population genetics 



This work was supported in part by grants from the Spanish Ministry of Health (FISS PI080838 and PI11/00807) and three different Mutua Madrileña Automovilista grants.


  1. 1.
    Sellier J, Sellier A (1993) Atlas des peuples d′Orient. Editions La Decouverte, ParisGoogle Scholar
  2. 2.
    Herodotus (1989) History. Gredos, MadridGoogle Scholar
  3. 3.
    Strabo (1991) Geography. Gredos, MadridGoogle Scholar
  4. 4.
    Rosen R (1992) Georgia: a sovereign country of the Caucasus. Odyssey Publications, Hong KongGoogle Scholar
  5. 5.
    Trombetti A (1925) Origine della lingua basca. Memorie della R. Acedemia de le Science dell’Instituto di Bologna. Coop Tipografica Azzoguidi, BolognaGoogle Scholar
  6. 6.
    Lafon R (1948) Correspondence basques–caucasiques. Eusko-Jakintza 2:359Google Scholar
  7. 7.
    Vogt H (1955) Le basque et le langues cuacasiques. Bulletin de la Societé de Linguistique de Paris 51:121Google Scholar
  8. 8.
    Bouda K (1955) L’euskaro-caucasique. Homenaje a Don Julio Urquijo vol III, Real Sociedad Vascongada de amigos del País, San Sebastian (Donostia)Google Scholar
  9. 9.
    Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  10. 10.
    Itoh Y, Mizuki N, Shimada T, Azuma F, Itakura M, Kashiwase K et al (2005) High-throughput DNA typing of HLA-A, -B, -C, and -DRB1 loci by a PCR-SSOP-Luminex method in the Japanese population. Immunogenetics 57:717–729PubMedCrossRefGoogle Scholar
  11. 11.
    Arnaiz-Villena A, Timon M, Corell A, Perez-Aciego P, Martin-Villa JM, Regueiro JR (1992) Primary immunodeficiency caused by mutations in the gene encoding the CD3-gamma subunit of the T-lymphocyte receptor. N Engl J Med 327:529–533PubMedCrossRefGoogle Scholar
  12. 12.
    Excoffier L, Slatkin M (1995) Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol 12:921–927PubMedGoogle Scholar
  13. 13.
    Imanishi T, Akaza T, Kimura A, Tokunaga K, Gojobori T (1992) Estimation of allele and haplotype frequencies for HLA and complement loci. In: Tsuji K, Aizawa M, Sasazuki T (eds) HLA 1991, 1st edn. Oxford University Press, Oxford, pp 76–79Google Scholar
  14. 14.
    Mattiuz PL, Ihde D, Piazza A, Ceppelini R, Wodmer WF (1970) New approaches to the population genetics and segregation analysis of the HLA system. Histocompatibility testing, 1970, Munksgaard, Copenhagen, pp 193–206Google Scholar
  15. 15.
    Imanishi T, Akaza T, Kimura A, Tokunaga K, Gojobori T (1992) Allele and haplotype frequencies for HLA and complement loci in various ethnic groups. In: Tsuji K, Aizawa M, Sasazuki T (eds) HLA 1991, 1st edn. Oxford University Press, Oxford, pp 1065–1220Google Scholar
  16. 16.
    Clayton J, Lonjou C (1997) Allele and Haplotype frequencies for HLA loci in various ethnic groups. In: Charron D (ed) Genetic diversity of HLA. Functional and medical implications, 1st edn. EDK, Paris, pp 665–820Google Scholar
  17. 17.
    Arnaiz-Villena A, Martinez-Laso J, Gomez-Casado E, Diaz-Campos N, Santos P, Martinho A et al (1997) Relatedness among Basques, Portuguese, Spaniards, and Algerians studied by HLA allelic frequencies and haplotypes. Immunogenetics 47:37–43PubMedCrossRefGoogle Scholar
  18. 18.
    Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425PubMedGoogle Scholar
  19. 19.
    Nei M (1972) Genetic distances between populations. Am Nat 106:283CrossRefGoogle Scholar
  20. 20.
    Nei M (1973) Analysis of gene diversity in subdivided populations. Proc Natl Acad Sci USA 70:3321–3323PubMedCrossRefGoogle Scholar
  21. 21.
    Nei M, Tajima F, Tateno Y (1983) Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data. J Mol Evol 19:153–170PubMedCrossRefGoogle Scholar
  22. 22.
    Young FW, Bann CM (1996) A visual statistics system. In: Stine RA, Fox J (eds) Statistical computing environments for social researches. Sage Publications, London, pp 207–236Google Scholar
  23. 23.
    Arnaiz-Villena A, Benmamar D, Alvarez M, Diaz-Campos N, Varela P, Gomez-Casado E et al (1995) HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques. Hum Immunol 43:259–268PubMedCrossRefGoogle Scholar
  24. 24.
    Martinez-Laso J, de Juan D, Martinez-Quiles N, Gomez-Casado E, Cuadrado E, Arnaiz-Villena A (1995) The contribution of the HLA-A, -B, -C and -DR, -DQ DNA typing to the study of the origins of Spaniards and Basques. Tissue Antigens 45:237–245PubMedCrossRefGoogle Scholar
  25. 25.
    Arnaiz-Villena A, Iliakis P, Gonzalez-Hevilla M, Longas J, Gomez-Casado E, Sfyridaki K et al (1999) The origin of Cretan populations as determined by characterization of HLA alleles. Tissue Antigens 53:213–226PubMedCrossRefGoogle Scholar
  26. 26.
    Gomez-Casado E, del Moral P, Martinez-Laso J, Garcia-Gomez A, Allende L, Silvera-Redondo C et al (2000) HLA genes in Arabic-speaking Moroccans: close relatedness to Berbers and Iberians. Tissue Antigens 55:239–249PubMedCrossRefGoogle Scholar
  27. 27.
    Arnaiz-Villena A, Dimitroski K, Pacho A, Moscoso J, Gomez-Casado E, Silvera-Redondo C et al (2001) HLA genes in Macedonians and the sub-Saharan origin of the Greeks. Tissue Antigens 57:118–127PubMedCrossRefGoogle Scholar
  28. 28.
    Arnaiz-Villena A, Karin M, Bendikuze N, Gomez-Casado E, Moscoso J, Silvera C et al (2001) HLA alleles and haplotypes in the Turkish population: relatedness to Kurds, Armenians and other Mediterraneans. Tissue Antigens 57:308–317PubMedCrossRefGoogle Scholar
  29. 29.
    Arnaiz-Villena A, Elaiwa N, Silvera C, Rostom A, Moscoso J, Gomez-Casado E et al (2001) The origin of Palestinians and their genetic relatedness with other Mediterranean populations. Hum Immunol 62:889–900PubMedCrossRefGoogle Scholar
  30. 30.
    Arnaiz-Villena A, Gomez-Casado E, Martinez-Laso J (2002) Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective. Tissue Antigens 60:111–121PubMedCrossRefGoogle Scholar
  31. 31.
    Sanchez-Velasco P, Leyva-Cobian F (2001) The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations. Tissue Antigens 58:223–233PubMedCrossRefGoogle Scholar
  32. 32.
    Arnaiz-Villena A, Alonso-Garcia J (2013) Caucasicos, Turcos, Mesopotamicos y Vascos. Editorial Complutense SA, MadridGoogle Scholar
  33. 33.
    Arnaiz-Villena A, Elaiwa N, Silvera C, Rostom A, Moscoso J, Gomez-Casado E, Allende L, Varela P, Martinez-Laso J The origin of Palestinians and their genetic relatedness with other Mediterranean populations (2001) stml Accesed 5 Apr 2013
  34. 34.
    McCauley JF, Schaber GG, Breed CS, Grotier MJ (1982) Subsurface valleys and geoarcheology of the Eastern Sahara revealed by shuttle radar. Science 218:1004–1020PubMedCrossRefGoogle Scholar
  35. 35.
    Currat M, Poloni ES, Sanchez-Mazas A (2010) Human genetic differentiation across the Strait of Gibraltar. BMC Evol Biol 10:237PubMedCrossRefGoogle Scholar
  36. 36.
    Dork T, El Harith EH, Stuhrmann M, Macek M Jr, Egan M, Cutting GR et al (1998) Evidence for a common ethnic origin of cystic fibrosis mutation 3120+1G–>A in diverse populations. Am J Hum Genet 63:656–662PubMedCrossRefGoogle Scholar
  37. 37.
    Papassavas EC, Spyropoulou-Vlachou M, Papassavas AC, Schipper RF, Doxiadis IN, Stavropoulos-Giokas C (2000) MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data. Hum Immunol 61:615–623PubMedCrossRefGoogle Scholar
  38. 38.
    Arnaiz-Villena A, Parga-Lozano C, Moreno E, Areces C, Rey D, Gomez-Prieto P (2010) The origin of Amerindians and the peopling of the Americas according to HLA genes: admixture with Asian and Pacific people. Curr Genomics 11:103–114PubMedCrossRefGoogle Scholar
  39. 39.
    Mizuki M, Ohno S, Ando H, Sato T, Imanishi T, Gojobori T et al (1997) Major histocompatibility complex class II alleles in Kazak and Han populations in the Silk Route of northwestern China. Tissue Antigens 50:527–534PubMedCrossRefGoogle Scholar
  40. 40.
    Mizuki N, Ohno S, Ando H, Sato T, Imanishi T, Gojobori T et al (1998) Major histocompatibility complex class II alleles in an Uygur population in the Silk Route of Northwest China. Tissue Antigens 51:287–292PubMedCrossRefGoogle Scholar
  41. 41.
    Farjadian S, Naruse T, Kawata H, Ghaderi A, Bahram S, Inoko H (2004) Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan. Tissue Antigens 64:581–587PubMedCrossRefGoogle Scholar
  42. 42.
    Hajjej A, Sellami MH, Kaabi H, Hajjej G, El Gaaied A, Boukef K et al (2011) HLA class I and class II polymorphisms in Tunisian Berbers. Ann Hum Biol 38:156–164PubMedCrossRefGoogle Scholar
  43. 43.
    Izaabel H, Garchon HJ, Caillat-Zucman S, Beaurain G, Akhayat O, Bach JF et al (1998) HLA class II DNA polymorphism in a Moroccan population from the Souss, Agadir area. Tissue Antigens 51:106–110PubMedCrossRefGoogle Scholar
  44. 44.
    Roitberg-Tambur A, Witt CS, Friedmann A, Safirman C, Sherman L, Battat S et al (1995) Comparative analysis of HLA polymorphism at the serologic and molecular level in Moroccan and Ashkenazi Jews. Tissue Antigens 46:104–110PubMedCrossRefGoogle Scholar
  45. 45.
    Martinez-Laso J, Gazit E, Gomez-Casado E, Morales P, Martinez-Quiles N, Alvarez M et al (1996) HLA DR and DQ polymorphism in Ashkenazi and non-Ashkenazi Jews: comparison with other Mediterraneans. Tissue Antigens 47:63–71PubMedCrossRefGoogle Scholar
  46. 46.
    Gonzalez-Galarza FF, Christmas S, Middleton D, Jones AR (2011) Allele frequency net: a database and online repository for immune gene frequencies in worldwide populations. Nucleic Acids Res 39:D913–D919PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Diego Rey
    • 1
  • Cristina Areces
    • 1
  • Javier Alonso-Rubio
    • 1
  • Mercedes Enríquez-de-Salamanca
    • 1
  • Sedeka Abd-El-Fatah-Khalil
    • 2
  • Nina Bendikuze
    • 3
  • Mercedes Fernández-Honrado
    • 2
  • Luz Barbolla
    • 2
  • José Manuel Martín-Villa
    • 1
  • Antonio Arnaiz-Villena
    • 1
    Email author
  1. 1.Department of ImmunologySchool of Medicine, Madrid Regional Blood Center, University ComplutenseMadridSpain
  2. 2.Department of HaematologyMadrid Regional Blood CenterMadridSpain
  3. 3.Institute for Clinical and Experimental MedicinePragueCzech Republic

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