Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Mar 15;89(6):2277–2281. doi: 10.1073/pnas.89.6.2277

Extensive genetic diversity in the HLA class II region of Africans, with a focally predominant allele, DRB1*1304.

A V Hill 1, C E Allsopp 1, D Kwiatkowski 1, T E Taylor 1, S N Yates 1, N M Anstey 1, J J Wirima 1, D R Brewster 1, A J McMichael 1, M E Molyneux 1, et al.
PMCID: PMC48640  PMID: 1347946

Abstract

Molecular HLA class II typing of greater than 1700 individuals from The Gambia in West Africa and Malawi in South-Central Africa revealed a striking diversity of HLA DRB-DQB haplotypes as defined by restriction fragment length polymorphism (RFLP); this diversity is twice as extensive as that found in northern Europeans. Despite this diversity, sequence and PCR/oligonucleotide analysis showed that the recently described variant DRB1*1304 is the commonest DRB1 allele in The Gambia. The sequence, geographical distribution, and RFLP association of this allele, together with homozygosity test results, suggest that DRB1*1304 may have arisen from DRB1*1102 and have reached its remarkably high frequency as a result of recent directional selection. The prevalence of this unusual allele has implications for trials of subunit vaccines in this area. The extensive and distinctive HLA class II region polymorphism in sub-Saharan Africans is consistent with evidence from other genetic loci implying an African origin of modern Homo sapiens.

Full text

PDF
2277

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allsopp C. E., Harding R. M., Taylor C., Bunce M., Kwiatkowski D., Anstey N., Brewster D., McMichael A. J., Greenwood B. M., Hill A. V. Interethnic genetic differentiation in Africa: HLA class I antigens in The Gambia. Am J Hum Genet. 1992 Feb;50(2):411–421. [PMC free article] [PubMed] [Google Scholar]
  2. Begovich A. B., McClure G. R., Suraj V. C., Helmuth R. C., Fildes N., Bugawan T. L., Erlich H. A., Klitz W. Polymorphism, recombination, and linkage disequilibrium within the HLA class II region. J Immunol. 1992 Jan 1;148(1):249–258. [PubMed] [Google Scholar]
  3. Bidwell J. L., Bidwell E. A., Savage D. A., Middleton D., Klouda P. T., Bradley B. A. A DNA-RFLP typing system that positively identifies serologically well-defined and ill-defined HLA-DR and DQ alleles, including DRw10. Transplantation. 1988 Mar;45(3):640–646. doi: 10.1097/00007890-198803000-00027. [DOI] [PubMed] [Google Scholar]
  4. Bowcock A. M., Bucci C., Hebert J. M., Kidd J. R., Kidd K. K., Friedlaender J. S., Cavalli-Sforza L. L. Study of 47 DNA markers in five populations from four continents. Gene Geogr. 1987 Apr;1(1):47–64. [PubMed] [Google Scholar]
  5. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  6. Cann R. L., Stoneking M., Wilson A. C. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1;325(6099):31–36. doi: 10.1038/325031a0. [DOI] [PubMed] [Google Scholar]
  7. Carlsson B., Wallin J., Böhme J., Möller E. HLA-DR-DQ haplotypes defined by restriction fragment analysis. Correlation to serology. Hum Immunol. 1987 Oct;20(2):95–113. doi: 10.1016/0198-8859(87)90025-5. [DOI] [PubMed] [Google Scholar]
  8. Cavalli-Sforza L. L., Piazza A., Menozzi P., Mountain J. Reconstruction of human evolution: bringing together genetic, archaeological, and linguistic data. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6002–6006. doi: 10.1073/pnas.85.16.6002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark A. G. Neutrality tests of highly polymorphic restriction-fragment-length polymorphisms. Am J Hum Genet. 1987 Nov;41(5):948–956. [PMC free article] [PubMed] [Google Scholar]
  10. Cullen C. G., Middleton D., Savage D. A. Frequency and associations of HLA class II TaqI allogenotypes in the Northern Ireland population. Hum Immunol. 1990 Oct;29(2):92–102. doi: 10.1016/0198-8859(90)90072-w. [DOI] [PubMed] [Google Scholar]
  11. Ewens W. J. The sampling theory of selectively neutral alleles. Theor Popul Biol. 1972 Mar;3(1):87–112. doi: 10.1016/0040-5809(72)90035-4. [DOI] [PubMed] [Google Scholar]
  12. Fernandez-Vina M., Shumway W., Stastny P. DNA typing for class II HLA antigens with allele-specific or group-specific amplification. II. Typing for alleles of the DRw52-associated group. Hum Immunol. 1990 May;28(1):51–64. doi: 10.1016/0198-8859(90)90102-u. [DOI] [PubMed] [Google Scholar]
  13. Fletcher J., Mijovic C., Odugbesan O., Mackay E., Bradwell A. R., Barnett A. H. HLA-DR and DQ DNA polymorphisms in subjects of Asian Indian and white Caucasian origin. Mol Immunol. 1988 Apr;25(4):411–417. doi: 10.1016/0161-5890(88)90036-3. [DOI] [PubMed] [Google Scholar]
  14. Higgs D. R., Wainscoat J. S., Flint J., Hill A. V., Thein S. L., Nicholls R. D., Teal H., Ayyub H., Peto T. E., Falusi A. G. Analysis of the human alpha-globin gene cluster reveals a highly informative genetic locus. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5165–5169. doi: 10.1073/pnas.83.14.5165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hill A. V., Allsopp C. E., Kwiatkowski D., Anstey N. M., Greenwood B. M., McMichael A. J. HLA class I typing by PCR: HLA-B27 and an African B27 subtype. Lancet. 1991 Mar 16;337(8742):640–642. doi: 10.1016/0140-6736(91)92452-8. [DOI] [PubMed] [Google Scholar]
  16. Hill A. V., Allsopp C. E., Kwiatkowski D., Anstey N. M., Twumasi P., Rowe P. A., Bennett S., Brewster D., McMichael A. J., Greenwood B. M. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991 Aug 15;352(6336):595–600. doi: 10.1038/352595a0. [DOI] [PubMed] [Google Scholar]
  17. Hughes A. L., Nei M. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature. 1988 Sep 8;335(6186):167–170. doi: 10.1038/335167a0. [DOI] [PubMed] [Google Scholar]
  18. Hurley C. K., Gregersen P., Steiner N., Bell J., Hartzman R., Nepom G., Silver J., Johnson A. H. Polymorphism of the HLA-D region in American blacks. A DR3 haplotype generated by recombination. J Immunol. 1988 Feb 1;140(3):885–892. [PubMed] [Google Scholar]
  19. Johnson A. H., Rosen-Bronson S., Hurley C. K. Heterogeneity of the HLA-D region in American blacks. Transplant Proc. 1989 Dec;21(6):3872–3873. [PubMed] [Google Scholar]
  20. Klitz W., Thomson G., Baur M. P. Contrasting evolutionary histories among tightly linked HLA loci. Am J Hum Genet. 1986 Sep;39(3):340–349. [PMC free article] [PubMed] [Google Scholar]
  21. Lee K. W., Hurley C. K., Hartzman R., Johnson A. H. The complexity of DRw6 and DR5 haplotypes in American blacks demonstrated by serology, cellular typing, and restriction fragment length polymorphism analysis. Hum Immunol. 1990 Nov;29(3):202–219. doi: 10.1016/0198-8859(90)90115-6. [DOI] [PubMed] [Google Scholar]
  22. Lee K. W., Johnson A. H., Hurley C. K. Two divergent routes of evolution gave rise to the DRw13 haplotypes. J Immunol. 1990 Nov 1;145(9):3119–3125. [PubMed] [Google Scholar]
  23. Martell R. W., Oudshoorn M., Arendse B., du Toit E. D. Polymorphism of DRw52 and its association with DRw11 and DRw12 in South African blacks (Negroes) and individuals of mixed ancestry (Cape coloreds). Hum Immunol. 1990 May;28(1):32–38. doi: 10.1016/0198-8859(90)90100-4. [DOI] [PubMed] [Google Scholar]
  24. Martell R. W., Oudshoorn M., May R. M., du Toit E. D. Restriction fragment length polymorphism of HLA-DRw53 detected in South African blacks and individuals of mixed ancestry. Hum Immunol. 1989 Dec;26(4):237–244. doi: 10.1016/0198-8859(89)90002-5. [DOI] [PubMed] [Google Scholar]
  25. Middleton D., Savage D. A., Cullen C., Martin J. Five new TaqI DRB1 polymorphisms. Hum Immunol. 1991 Jun;31(2):145–147. doi: 10.1016/0198-8859(91)90018-5. [DOI] [PubMed] [Google Scholar]
  26. Nei M., Livshits G. Genetic relationships of Europeans, Asians and Africans and the origin of modern Homo sapiens. Hum Hered. 1989;39(5):276–281. doi: 10.1159/000153872. [DOI] [PubMed] [Google Scholar]
  27. Okoye R. C., Ollier W., Jaraquemada D., Awad J., Navarrete C., Cutbush S., Carthy D., Dos-Santos A., Festenstein H. HLA-D region heterogeneity in a Nigerian population. Tissue Antigens. 1989 Apr;33(4):445–456. doi: 10.1111/j.1399-0039.1989.tb01693.x. [DOI] [PubMed] [Google Scholar]
  28. Olerup O., Troye-Blomberg M., Schreuder G. M., Riley E. M. HLA-DR and -DQ gene polymorphism in West Africans is twice as extensive as in north European Caucasians: evolutionary implications. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8480–8484. doi: 10.1073/pnas.88.19.8480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Oudshoorn M., Martell R. W., Arendse B., du Toit E. D. Unusual HLA-DR,DQ haplotypes found in South African families of black, Asian Indian, and mixed ancestral origin. Hum Immunol. 1991 May;31(1):14–19. doi: 10.1016/0198-8859(91)90043-9. [DOI] [PubMed] [Google Scholar]
  30. Piazza A., Sgaramella-Zonta L., Gluckman P., Cavalli-Sforza L. L. The Fifth Histocompatibility Workshop gene frequency data: a phylogenetic analysis. Tissue Antigens. 1975 Jun;5(5):445–463. doi: 10.1111/j.1399-0039.1975.tb01489.x. [DOI] [PubMed] [Google Scholar]
  31. Rønningen K. S., Spurkland A., Markussen G., Iwe T., Vartdal F., Thorsby E. Distribution of HLA class II alleles among Norwegian Caucasians. Hum Immunol. 1990 Dec;29(4):275–281. doi: 10.1016/0198-8859(90)90041-m. [DOI] [PubMed] [Google Scholar]
  32. Saiki R. K., Bugawan T. L., Horn G. T., Mullis K. B., Erlich H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. doi: 10.1038/324163a0. [DOI] [PubMed] [Google Scholar]
  33. Serjeantson S. W., White B. S., Jazwinska E. C., Yenchitsomanus P. T., Mickleson K. N., Trent R. J. HLA-DR and -DQ DNA polymorphisms: new linkage relationships established by RFLP genomic typing in Polynesians and Melanesians. Hum Immunol. 1987 Oct;20(2):145–153. doi: 10.1016/0198-8859(87)90028-0. [DOI] [PubMed] [Google Scholar]
  34. Stringer C. B., Andrews P. Genetic and fossil evidence for the origin of modern humans. Science. 1988 Mar 11;239(4845):1263–1268. doi: 10.1126/science.3125610. [DOI] [PubMed] [Google Scholar]
  35. Wainscoat J. S., Hill A. V., Boyce A. L., Flint J., Hernandez M., Thein S. L., Old J. M., Lynch J. R., Falusi A. G., Weatherall D. J. Evolutionary relationships of human populations from an analysis of nuclear DNA polymorphisms. Nature. 1986 Feb 6;319(6053):491–493. doi: 10.1038/319491a0. [DOI] [PubMed] [Google Scholar]
  36. Watterson G. A. The homozygosity test of neutrality. Genetics. 1978 Feb;88(2):405–417. doi: 10.1093/genetics/88.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wordsworth B. P., Allsopp C. E., Young R. P., Bell J. I. HLA-DR typing using DNA amplification by the polymerase chain reaction and sequential hybridization to sequence-specific oligonucleotide probes. Immunogenetics. 1990;32(6):413–418. doi: 10.1007/BF00241635. [DOI] [PubMed] [Google Scholar]
  38. du Toit E. D., MacGregor K. J., Taljaard D. G., Oudshoorn M. HLA-A, B, C, DR and DQ polymorphisms in three South African population groups: South African Negroes, Cape Coloureds and South African Caucasoids. Tissue Antigens. 1988 Mar;31(3):109–125. doi: 10.1111/j.1399-0039.1988.tb02072.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES