OJGen  Vol.4 No.2 , April 2014
Diversity and Frequencies of HLA Class I and Class II Genes of an East African Population

Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.

Cite this paper: Peterson, T. , Bielawny, T. , Lacap, P. , Hardie, R. , Daniuk, C. , Mendoza, L. , Thavaneswaran, S. , Kariri, T. , Kimani, J. , Wachihi, C. , Kimani, M. , Ball, T. , Plummer, F. and Luo, M. (2014) Diversity and Frequencies of HLA Class I and Class II Genes of an East African Population. Open Journal of Genetics, 4, 99-124. doi: 10.4236/ojgen.2014.42013.

[1]   Azurdia, R.M., Luzzi, G.A., Byren, I., et al. (1999) Lichen Sclerosus in Adult Men: A Study of HLA Associations and Susceptibility to Autoimmune Disease. British Journal of Dermatology, 140, 79-83.

[2]   Gladman, D.D., Anhorn, K.A., Schachter, R.K. and Mervart, H. (1986) HLA Antigens in Psoriatic Arthritis. The Journal of Rheumatology, 13, 586-592.

[3]   Rohowsky-Kochan, C., Skurnick, J., Molinaro, D. and Louria, D. (1998) HLA Antigens Associated with Susceptibility/Resistance to HIV-1 Infection. Human Immunology, 59, 802-815.

[4]   Tishkoff, S.A., Reed, F.A., Friedlaender, F.R., et al. (2009) The Genetic Structure and History of Africans and African Americans. Science, 324, 1035-1044.

[5]   Luo, M., Embree, J., Ramdahin, S., et al. (2002) HLA-A and HLA-B in Kenya, Africa: Allele Frequencies and Identification of HLA-B*1567 and HLA-B*4426. Tissue Antigens, 59, 370-380.

[6]   Sanchez-Mazas, A., Steiner, Q.G., Grundschober, C. and Tiercy, J.M. (2000) The Molecular Determination of HLA-Cw Alleles in the Mandenka (West Africa) Reveals a Close Genetic Relationship between Africans and Europeans. Tissue Antigens, 56, 303-312.

[7]   Luo, M., Blanchard, J., Pan, Y., Brunham, K. and Brunham, R.C. (1999) High-Resolution Sequence Typing of HLA-DQA1 and-DQB1 Exon 2 DNA with Taxonomy-Based Sequence Analysis (TBSA) Allele Assignment. Tissue Antigens, 54, 69-82.

[8]   Middleton, D., Menchaca, L., Rood, H. and Komerofsky, R. (2003) New Allele Frequency Database: Tissue Antigens, 61, 403-407.

[9]   Luo, M., Blanchard, J., Brunham, K., et al. (2001) Two-Step High Resolution Sequence-Based HLA-DRB Typing of Exon 2 DNA with Taxonomy-Based Sequence Analysis Allele Assignment. Human Immunology, 62, 1294-310.

[10]   Flores-Villanueva, P.O., Yunis, E.J., Delgado, J.C., et al. (2001) Control of HIV-1 Viremia and Protection from AIDS Are Associated with HLA-Bw4 Homozygosity. Proceedings of the National Academy of Sciences of the United States of America, 98, 5140-5145.

[11]   Hill, A.V., Allsopp, C.E., Kwiatkowski, D., et al. (1991) Common West African HLA Antigens Are Associated with Protection from Severe Malaria. Nature, 352, 595-600.

[12]   Kijak, G.H., Walsh, A.M., Koehler, R.N., et al. (2009) HLA Class I Allele and Haplotype Diversity in Ugandans Supports the Presence of a Major East African Genetic Cluster. Tissue Antigens, 73, 262-269.

[13]   Peterson, T.A., Kimani, J., Wachihi, C., et al. (2013) HLA Class I Associations with Rates of HIV-1 Seroconversion and Disease Progression in the Pumwani Sex Worker Cohort. Tissue Antigens, 81, 93-107.

[14]   Hardie, R.A., Knight, E., Bruneau, B., et al. (2008) A Common Human Leucocyte Antigen-DP Genotype Is Associated with Resistance to HIV-1 Infection in Kenyan Sex Workers. AIDS, 22, 2038-2042.

[15]   Cao, K., Moormann, A.M., Lyke, K.E., et al. (2004) Differentiation between African Populations Is Evidenced by the Diversity of Alleles and Haplotypes of HLA Class I Loci. Tissue Antigens, 63, 293-325.

[16]   Canossi, A., Piancatelli, D., Aureli, A., et al. (2010) Correlation between Genetic HLA Class I and II Polymorphisms and Anthropological Aspects in the Chaouya Population from Morocco (Arabic Speaking). Tissue Antigens, 76, 177-193.

[17]   Dunn, R.R., Davies, T.J., Harris, N.C. and Gavin, M.C. (2010) Global Drivers of Human Pathogen Richness and Prevalence. Proceedings of the Royal Society: Biological Sciences, 277, 2587-2595.

[18]   Isabey, E.P., Pham, H.M., Peterson, T.A., Brunham, R.C., Luo, M. and Plummer, F.A. (2011) Identification of a Novel HLA-A Allele, A*29:28, in an East African Population. Tissue Antigens, 78, 451-452.

[19]   Luo, M., Blanchard, J., Maclean, I. and Brunham, R. (1999) Identification of a Novel HLA-DQA1 Allele (DQA1*0106) by Sequence-Based DQA1 Typing. Tissue Antigens, 53, 595-596.

[20]   Luo, M., Blanchard, J., Maclean, I. and Brunham, R. (1999) Identification of a Novel DQB1 Allele DBQ1*0616. Tissue Antigens, 53, 381-382.

[21]   Luo, M., Blanchard, J., Maclean, I. and Brunham, R. (2001) Identification of a Novel DRB1 Allele, DRB1*1112, by Sequence-Based DRB Typing. Tissue Antigens, 57, 85-86.

[22]   Luo, M., Cohen, C.R., Narayansingh, M.J., et al. (2004) Identification of a Novel HLA-DQA1 Null Allele, DQA1*0403N, from an East African Woman. Tissue Antigens, 63, 609-611.

[23]   Luo, M., Mao, X. and Plummer, F.A. (2005) Identification of Four Novel HLA-B Alleles, B*1590, B*1591, B*2726, and B*4705, from an East African Population by High-Resolution Sequence-Based Typing. Tissue Antigens, 65, 187-191.

[24]   Peterson, T.A., Luo, M., Mao, X., Brunham, R.C. and Plummer, F.A. (2008) Identification of a Novel DPA1 Allele, DPA1*010602, in an East African Population. Human Immunology, 69, 885-886.

[25]   Turk, W.J., Mao, X.J., Bielawny, T., Brunham, R., Luo, M. and Plummer, F.A. (2008) Identification of Novel Human Leukocyte Antigen G Alleles in an East African Population by High-Resolution Sequence-Based Typing. Human Immunology, 69, 426-429.

[26]   Ejsmond, M.J., Babik, W. and Radwan, J. (2010) MHC Allele Frequency Distributions under Parasite-Driven Selection: A Simulation Model. BMC Evolutionary Biology, 10, 332.