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Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2000 Aug;15(Suppl 1):65–77. doi: 10.1007/BF02867546

The HLA genes and their diverse polymorphism

N K Mehra 1,
PMCID: PMC3454072  PMID: 23105270

Abstract

Advanced DNA level studies based on HLA class II sequence analysis have revealed considerable diversity in HLA among Asian Indians. High resolution typing of specific alleles such as DR2 and DR4 in the HLA class II region by PCR-SSP or SSOP hybridization and their associated DR-DQ haplotypes have helped to detect unique haplotypes and novel alleles which have subsequently been confirmed by sequencing. Incidentally, remarkable stability has been maintained in several other DRB1 alleles viz. DR1, DR7, DR9 and DR10. The ARMS-PCR technology has been found to be particularly useful for typing HLA-A, HLA-B and HLA-Cw alleles. These technologies are far superior over serological methods. Our studies have shown remarkable heterogeneity of common HLA-A and B alleles in Asian Indians. Molecular subtyping of HLA-A2 revealed that subtype A*0211 is found only in Indian population and may be the result of selection pressure in this population. Investigations into polymorphism in the HLA-B27 gene revealed that subtypes common both to the western caucasians and orientals occur in the Indian population. It is apparent that the population of the Indian subcontinent, placed as it is between the Caucasoids and Negroids on one hand and Australoids and Mongoloids on the other, provides a rich source of many HLA haplotypes. While the most frequent Caucasian haplotypes occur with a reasonable frequency in Asian Indians, those found predominantly in other ethnic groups (e.g., australian Aborigines and populations of Oceania, China and Japan) are also detected. Knowledge on this is most important for donor selection during organ and bone marrow transplantation and for designing MHC targeted vaccines in specific diseases.

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References

  • 1.Madden D.R., Garboczi D.N., Wiley D.C. The antigenic identity of peptide-MHC complexes-a comparison of the conformations of five viral peptides presented by HLA-A2. Cell. 1993;75:693–708. doi: 10.1016/0092-8674(93)90490-H. [DOI] [PubMed] [Google Scholar]
  • 2.Stern L.J., Brown J.H., Jardetzky T.S., Gorga J.C., Urban R.G., Strominger J.L., Wiley D.C. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature. 1994;368:215–221. doi: 10.1038/368215a0. [DOI] [PubMed] [Google Scholar]
  • 3.Stern L.J., Wiley D.C. Antigenic peptide binding by class I and class II histocompatibility proteins. Structure. 1994;2:245–251. doi: 10.1016/S0969-2126(00)00026-5. [DOI] [PubMed] [Google Scholar]
  • 4.Snell G. Methods for the study of the histocompatibility genes. J. Genet. 1948;49:87–108. doi: 10.1007/BF02986826. [DOI] [PubMed] [Google Scholar]
  • 5.Lamm L.U., Olaisen B. Report of the committee on the genetic constitution of chromosome 5 and 6. Cytogenet. Cell Genet. 1985;40:128–155. doi: 10.1159/000132172. [DOI] [PubMed] [Google Scholar]
  • 6.Campbell R.D., Trowsdale J. Map of the human MHC. Immunology Today. 1993;14:349–352. doi: 10.1016/0167-5699(93)90234-C. [DOI] [PubMed] [Google Scholar]
  • 7.Klein J. Origin of major histocompatibility complex polymorphism. The transpecies hypothesis. Human Immunol. 1987;19:155–162. doi: 10.1016/0198-8859(87)90066-8. [DOI] [PubMed] [Google Scholar]
  • 8.Bjorkman P.J., Saper M.A., Samraoui B., Bennett W.S., Strominger J.L., Wiley D.C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987;329:506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  • 9.Bjorkman P.J., Saper M.A., Samraoui B., Bennett W.S., Strominger J.L., Wiley D.C. The foreign antigen binding site and T-cell recognition regions of class I histocompatibility antigens. Nature. 1987;329:512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  • 10.Brown J.H., Jardetzky T.S., Gorga J.C., Stern L.J., Urban R.G., Strominger J.L., Wiley D.C. Three dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature. 1993;364:33–39. doi: 10.1038/364033a0. [DOI] [PubMed] [Google Scholar]
  • 11.Spies T., Bresnahan M., Sands J., Strominger J.L. A new cluster of genes within the human major histocompatibility complex. Science. 1989;243:214–217. doi: 10.1126/science.2911734. [DOI] [PubMed] [Google Scholar]
  • 12.Trowsdale J., Hanson I., Mockridge I., Beck S., Townsend A., Kelly A. Sequences encoded in the class II region of the MHC related to the ‘ABC’ super-family of transporters. Nature. 1990;348:741–743. doi: 10.1038/348741a0. [DOI] [PubMed] [Google Scholar]
  • 13.Monaco J.J., McDevitt H.O. The LMP antigens: a stable MHC-controlled multisubunit protein complex. Hum Immunol. 1986;15:416–426. doi: 10.1016/0198-8859(86)90019-4. [DOI] [PubMed] [Google Scholar]
  • 14.Bhasin M.K., Walter H., Danker-Hopfe H. People of India: an investigation of biological variability in ecological, ethnoeconomic and linguistic groups. New Delhi: Kamla Raj Enterprises; 1994. [Google Scholar]
  • 15.Singal D.P., Pitchappan R.M., Agarwal S., Mehra N.K., Dupont B., Mackintosh P., Suzuki K. Distribution of HLA antigens in Asian Indians. In: Tsuji K, Aisawa M, Sasazuki T, editors. HLA 1991. Oxford: Oxford University Press; 1992. pp. 658–660. [Google Scholar]
  • 16.Mehra N.K., Rajalingam, R., Giphart, M.J. (1996) Generation of DR51 associated DQA1, DQB1, haplotypes in Asian Indians. Tissue Antigens. 47-85-89. [DOI] [PubMed]
  • 17.Mehra N.K., Taneja V., Kailash S., Raizada N., Vaidya M.C. Distribution of HLA antigens in a sample of the North Indian Hindu population. Tissue Antigen. 1986;27:64–67. doi: 10.1111/j.1399-0039.1986.tb01500.x. [DOI] [PubMed] [Google Scholar]
  • 18.Pitchappan R.M., Manickasundari M., Kakkanaih V.N., Mahendren V., Brahamajothi V., Chandramohan R., Subash Chander M., Rajaseker R. HLA antigens in Sourastrans of Madurai. In: Aizawa M., Natori T, Wakisaka A., Konoeda Y, editors. HLA in Asia Oceania, proceedings of III Asia Oceania Histocompatibility Workshop and conference. Sapporo, Japan: Hokkaido University Press; 1986. pp. 539–542. [Google Scholar]
  • 19.Mehra N.K., Verduijn W., Taneja V., Drabbels J., Singh S.P.N., Giphart M. Analysis of HLA-DR associated polymorphisms by oligonucleotide hybridization in an Asian Indian population. Human Immunol. 1991;32:241–247. doi: 10.1016/0198-8859(91)90086-O. [DOI] [PubMed] [Google Scholar]
  • 20.Mehra N.K., Bouwens A.G.M., Naipal A., Rajalingam R., Grubic Z., Taneja V., Tilanus M.G.J., Giphart M.J. Asian Indian HLA-Dr2, DR4 and DR52 related DR-DQ genetypes analysed by PCR based non-radioactive oligonucleotide typing: unique haplotypes and a novel DR4 subtypes. Human Immunol. 1994;39:202–210. doi: 10.1016/0198-8859(94)90261-5. [DOI] [PubMed] [Google Scholar]
  • 21.Mehra N.K., Rajalingam R., Kanga U., McEnemy L., Cullen C., Agarwal S., Middleton D., Pollack M.S., Amirzargar A., Singal D.P. Genetic diversity of HLA in the populations of India, Sri Lanka and Iran. In: Dominique Charron., editor. Genetic Diversity of HLA: Functional and Medical Implications. Paris: EDK Publishers; 1997. pp. 314–320. [Google Scholar]
  • 22.Kanga U., Mehra N.K., Larrea C.L., Lardy N.M., Kumar A., Feltkamp T.E.W. Seronegative spondyloarthropathies and HLA-B27 subtypes: A study in Asian Indians. Clinical Rheumatology. 1996;15:13–18. doi: 10.1007/BF03342638. [DOI] [PubMed] [Google Scholar]
  • 23.Taneja V., Giphart M.J., Verduijn W., Naipal A., Malaviya A.N., Mehra N.K. Polymorphism of HLA-DRB,-DQA1 and-DQB1 in rheumatoid arthritis in Asian Indians. Association with DRB1*0405 and DRB1*1001. Human Immunol. 1996;46:35–41. doi: 10.1016/0198-8859(95)00165-4. [DOI] [PubMed] [Google Scholar]
  • 24.Arnaiz-Villena A., Chandanayingyong D., Chiewsilp P., Fan L., Fauehet R., Fumiaki N., Gomez-Casado E., Guo S.S., Gyodi E., Hammond M., Jersild C., Juji T., Lepage V., Martinetti M., Martinez-Laso J., Mehra N., Penzes M., Rajalingam R., Rajczy K., Tokunaga . HLA-G polymorphism: 12th International Histocompatibility workshop study. In: Genetic Diversity of HLA: Functional and Medical Implications, editor. Dominique Charron. Paris: EDK Publishers; 1997. pp. 155–159. [Google Scholar]
  • 25.Arnaiz-Villena A., Chandanayingyong D., Chiewsilp P., Diaz-Campos, Fan L., Fauehet R., Fumiaki N., Guo S.S., Gyodi E., Hammond M., Jersild C., Juji T., Lepage V., Martinetti M., Martinez-Laso J., Mehra N., Penzes M., Rajalingam R., Rajczy K., Tokunaga . HLA-E polymorphism: 12th International Histocompatibility workshop study. In: Genetic Diversity of HLA: Functional and Medical implications, editor. Dominique Charron. Paris: EDK Publishers; 1997. pp. 151–154. [Google Scholar]

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