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Analysis of HLA gene polymorphisms in East Africans reveals evidence of gene flow in two Semitic populations from Sudan

European Journal of Human Genetics volume 29, pages 1259–1271 (2021)Cite this article

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Abstract

Sudan, a northeastern African country, is characterized by high levels of cultural, linguistic, and genetic diversity, which is believed to be affected by continuous migration from neighboring countries. Consistent with such demographic effect, genome-wide SNP data revealed a shared ancestral component among Sudanese Afro-Asiatic speaking groups and non-African populations, mainly from West Asia. Although this component is shared among all Afro-Asiatic speaking groups, the extent of this sharing in Semitic groups, such as Sudanese Arab, is still unknown. Using genotypes of six polymorphic human leukocyte antigen (HLA) genes (i.e., HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1), we examined the genetic structure of eight East African ethnic groups with origins in Sudan, South Sudan, and Ethiopia. We identified informative HLA alleles using principal component analysis, which revealed that the two Semitic groups (Gaalien and Shokrya) constituted a distinct cluster from the other Afro-Asiatic speaking groups in this study. The HLA alleles that distinguished Semitic Arabs co-exist in the same extended HLA haplotype, and those alleles are in strong linkage disequilibrium. Interestingly, we find the four-locus haplotype “C*12:02-B*52:01-DRB1*15:02-DQB1*06:01” exclusively in non-African populations and it is widely spread across Asia. The identification of this haplotype suggests a gene flow from Asia, and likely these haplotypes were brought to Africa through back migration from the Near East. These findings will be of interest to biomedical and anthropological studies that examine the demographic history of northeast Africa.

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Fig. 1: Sampling locations in this study.
Fig. 2: Principal component analysis of eight east African populations based on allele frequencies of six HLA loci.
Fig. 3: Frequency of informative HLA alleles.
Fig. 4: Pairwise LD (D’) between HLA allele of common haplotypes among Gaalien and Shokrya.

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Acknowledgements

The authors would like to thank all participants who generously donated their DNA samples. MGN was supported by a Spinoza grant of the Netherlands Organization for scientific research.

Author information

Author notes

  1. Waleed Aamer

    Present address: Human Genetics Department, Precision Medicine Program, Research Branch, Sidra Medicine, Doha, Qatar

  2. Hirofumi Nakaoka

    Present address: Department of Cancer Genome Research, Sasaki Institute, Sasaki Foundation, Chiyoda-ku, Tokyo, Japan

Authors and Affiliations

  1. Human Genetics Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Shizuoka, Japan

    Waleed Aamer, Hirofumi Nakaoka & Ituro Inoue

  2. Department of Genetics, The Graduate University for Advanced Studies, SOKENDAI, Mishima, Shizuoka, Japan

    Waleed Aamer, Hirofumi Nakaoka & Ituro Inoue

  3. Banoon ART and Cytogenetics Centre, Bahrain Defence Force Hospital, Riffa, Kingdom of Bahrain

    Hisham Y. Hassan

  4. Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan

    Kazuyoshi Hosomichi

  5. Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands

    Martin Jaeger & Mihai G. Netea

  6. Public and Tropical Health Programmes, University of Medical Sciences and Technology, Khartoum, Sudan

    Hanan Tahir

  7. Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman

    Mohammed H. Abdelraheem

  8. Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany

    Mihai G. Netea

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Contributions

II, NH, and AW conceived and designed the study. II and NMG provided materials and supervision. AW performed the experiments with contribution from HHY, and JM. HHY collected participants data with contribution from TH. AW, HN, performed HLA data analysis and interpretation with contribution from HHY, HK, and AMH. All authors read and approved the final manuscript.

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Correspondence to Ituro Inoue.

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Aamer, W., Hassan, H.Y., Nakaoka, H. et al. Analysis of HLA gene polymorphisms in East Africans reveals evidence of gene flow in two Semitic populations from Sudan. Eur J Hum Genet 29, 1259–1271 (2021). https://doi.org/10.1038/s41431-021-00845-6

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