the genetic diversity of hla drb1* alleles among indian ...world scientific news 114 (2018) 15-29...

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( Received 08 October 2018; Accepted 24 October 2018; Date of Publication 31 October 2018 )

WSN 114 (2018) 15-29 EISSN 2392-219

The genetic diversity of HLA DRB1* alleles among Indian and African populations

R. Nandakumar

Department of Zoology, St. Joseph University, Ikishe Model Village, Dimapur, Nagaland, 797115, India

E-mail address: [email protected]

ABSTRACT

The HLA system is highly polymorphic and commonly used as a marker to understand core

population genetical aspects such as stratification, human migration, predisposition to diseases and

tissue transplantation compatibility. Although HLA alleles are generally treated as equidistant molecular

units in population genetic studies, the diversity of DNA allelic frequencies among populations is also

considered to be crucial to interpret the observed HLA polymorphisms. This study compares the

variation of HLA DRB1 alleles across various subgroups of both Indian and African Populations, using

their respective allelic frequencies. The HLA DRB1 allelic frequencies for 3,153 individuals of 32

subgroups of both Indian and African populations, were collected from the Allele Frequency Net

Database (AFND). Correlation matrix and Grid diagram were compiled using the R statistical package.

Allele frequencies were analyzed for the respective population subgroups using XLSTAT. The North

East Indian populations were completely devoid of HLA DRB1* 16, which is fairly present in south

Indian populations. The South Indian populations harbor both HLA DRB1* 10 and HLA DRB1* 15 at

relatively higher levels but are very scarce of HLA DRB1* 07, HLA DRB1* 09, HLA DRB1* 12 and

HLA DRB1* 13. The alleles HLA DRB1* 03, HLA DRB1* 04 and HLA DRB1* 07 could represent an

epicenter for the admixture of African, North-East Indian and South Indian populations.

Keywords: HLA DRB1, Population Genetics, Indian and African populations, Demography,

Migration, Admixture

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1. INTRODUCTION

The Human Leukocyte Antigen (HLA) loci are among the most polymorphic genes

currently described in the human genome, with more than 4,000 observed alleles according to

the released IMGT/HLA database.

These loci are located on the short arm of chromosome 6 within the Major

Histocompatibility Complex (MHC) and are extensively studied due to their critical role in

organ or hematopoietic stem cell transplantation and clinical medicine. Allelic variation of HLA

genes is characterized at the DNA sequence level since the mid of 1990s [1-3]. Each MHC class

II gene has many possible variations, allowing the immune system to react to a wide range of

foreign invaders. Researchers have identified hundreds of different versions (alleles) of the

HLA-DRB1 gene, each of which is given a particular number (such as HLA-DRB1*04:01) [4-

10].

This present study compares the HLA DRB1* allele frequencies of various Indian and

African subgroups which could verify the population admixture within these groups and

validate the ‘Out-of Africa‘ hypothesis.

2. MATERIALS AND METHODS

2. 1. Allelic Frequencies Data

Allelic frequencies for the respective population were collected from the Allele

Frequency Net Database (AFND) which provides a central and open-access source for the allele

frequencies data of different polymorphic areas of the human genome

(http://www.allelefrequencies.net/). Additional data were collected from the published report

of Balakrishnan K. et al (2012) [7].

2. 2. Statistical analyses

The R statistical package (http://www.r-project.org/) was used to compute the correlation

matrix (Table 01) and Grid diagram (Figure 01) depicting the correlations among all population

subgroups. The DRB1* alleles were aligned according to their respective frequencies in

populations using MS-Excel (Table 02). The multiple Moroccon population group was not

considered for analyses, because of the lack of sample compatibility.

3. RESULTS

According to the correlation matrix and grid diagram, no significant relationship is

evident between the study populations. But the relative frequencies of HLA DRB1* 16 allele

was found to be almost absent among the North-East Indian populations but was relatively

higher among the South Indian populations. The South Indian populations contain HLA DRB1*

10 and HLA DRB1* 15 alleles at higher frequency levels, but have low frequencies of HLA

DRB1* 07, HLA DRB1* 09, HLA DRB1* 12 and HLA DRB1* 13.


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4. DISCUSSION

We analyzed the nucleotide diversity of one HLA genes (HLA - DRB1) using the allele

frequencies, in more than 3,153 individuals from about 32 populations of both African and

Indian continents. We first applied an extensive treatment of the data at the genotypic and

nucleotide levels to ensure compatibility with the latest updates of the official HLA allele

nomenclature. We then analyzed the DNA molecular variation of HLA alleles at several

geographic scales (i.e., Global, continental, and regional), to investigate its congruence with the

observed genetic diversity profiles based on allelic frequencies and explore the additional

information brought by DNA sequences. Despite the complex evolution of the HLA system and

the difficulty to disentangle the effects of molecular mechanisms such as balancing selection,

gene conversion and recombination, our results could suggest a strong influence of

demographic factors and human migrations upon the polymorphism.

In this study, the allele HLA DRB1* 04 is equally distributed (Fig. 04) in North-East

Indian, Moroccon and South Indian populations at relatively higher frequencies. Since the

North-East Indian and South Indian populations are demographically and geographically

distant, this unique allelic distributions must be considered to hypothesize any population

stratification relationships. Supporting this claim, the HLA DRB1* 14 allele (Fig. 12) also is

non-randomly distributed among the NE Indian and south Indian populations. These two

distributions seem to show a pattern of North East Indian and South Indian settlements.

Interestingly, the alleles HLA DRB1* 08, HLA DRB1* 11 and HLA DRB1* 13 (Fig. 6, 9 and

11) are distributed, at higher frequencies , across the Burkina Faso and North East Indian tribes,

suggesting the probable mixture of populations from Sub-Saharan Africa and India.

5. CONCLUSION

Altogether, these speculative comparisons suggest that the HLA DRB1* 04, HLA DRB1*

08, HLA DRB1* 11 and HLA DRB1* 13 represent an unique centre of admixture of

demographically distant populations. Yet, more population samples, sophisticated statistical

analyses with larger cohorts are strongly recommended to validate and extend these

observations.

Acknowledgments

We thank the University Grants Commision (UGC), New Delhi for their financial support to conduct this study.

References

[1] Buhler S, Sanchez-Mazas A (2011). HLA DNA Sequence Variation among Human

Populations: Molecular Signatures of Demographic and Selective Events. PLoS ONE

6(2): e14643. doi:10.1371/journal.pone.0014643

[2] Bunce M, Young N, Welsh K (1997). Molecular HLA Typing- The Brave New World.

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[3] Marsh S, Parham P, Barber L (2000). The HLA Facts Book Academic Press. 398 p.

[4] Steven G. E. Marsh (2008). Nomenclature for Factors of the HLA System, Update June

2008. Tissue Antigens Volume 72, Issue 3 September 2008 Pages 224-226

[5] Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, et al. (2005).

Nomenclature for factors of the HLA system, 2004. Tissue Antigens 65: 301–369.

[6] Robinson J, Marsh SG (2007). The IMGT/HLA database. Methods Mol. Biol 409: 43–

60.7.

[7] Balakrishnan. K et al., (2012). Gradients in Distribution of HLA – DRB1* Alleles in

Castes and Tribes of South India. Int J Hum Genet, 12(1): 45-55

[8] Solberg O. D., Mack S. J., Lancaster A. K., Single R. M., Tsai Y., Sanchez-Mazas A.,

Thomson G. (2008). Balancing selection and heterogeneity across the classical human

leukocyte antigen loci: a meta-analytic review of 497 population studies. Hum.

Immunol. 69, 443–464. doi:10.1016/j.humimm.2008.05.001

[9] Sanchez-Mazas A., et al. (2011). Immunogenetics as a tool in anthropological studies.

Immunology 133, 143–164. doi:10.1111/j.1365-2567.2011.03438.x

[10] M. J. Chen, C. C. Chu, M. H. Shyr, C. L. Lin, P. Y. Lin and K. L. Yang, Detection of a

rare Caucasoid HLA-DRB1*0337 in a Taiwanese bone marrow donor using sequence-

based typing method, International Journal of Immunogenetics, 37, 1, (1), (2010).

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https://onlinelibrary.wiley.com/toc/13990039/2008/72/3


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Table 1. Correlation matrix values for all the study populations


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Figure 1. Grid diagram for the comparison HLA DRB1 polymorphism among Indian and

Africa populations using correlation matrix


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Column 1 - Andhra Pradesh Brahmin: Column 2 - Andhra Pradesh Sunni: Column 3 - Andhra

Pradesh Golla: Column 4 – North East Kayastha: Column 5 – North East Lachung: Column

6 – North East Mathur: Column 7 – North East Mach: : Column 8 - North East Rajbanshi :

Column 9 – North East Rastogi: : Column 10 – North East Shia: Column 11 – North East

Sunni: Column 12 – North East Vaish: Column 13 - Mumbai Maratha : Column 14 -

Tamilnadu Kannikaran: Column 15 - Tamilnadu Paliyar: Column 16 - Tamilnadu Pallar:

Column 17 Tamilnadu Narikkuravar: Column 18 -Tamilnadu Kallar :Column 19 -Tamilnadu

Vanniyar: Column 20 - Tamilnadu V.Goundar : Column 21 - Tamilnadu Sourashtra: Column

22 - Tamilnadu Iyer :Column 23 - Kerela Namboothiri : Column 24 - Kerela Nair: Column

25 -Tamilnadu Yadavas: Column 26 -Tamilnadu P.Kallar: Column 27 - Morocco Nador

Metasa: Column 28 - Morocco Pops: Column 29 - Morocco Settat Chaouga:Column 30 -

Burkina Faso Fulani: Column 31 - Burkina Faso Mossi: Column 32 - Burkina Faso Rimaibe.

HLA DRB1* allelic frequencies to the corresponding populations


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HLA DRB1* allelic frequencies – Continued


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Table 2. Indian and African population subgroups with their HLA DRB1* alleles


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Table 2. Continue


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Table 2. Continue


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Table 2. Continue


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Table 2. Continue


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Table 2. Continue

the genetic diversity of hla drb1* alleles among indian ...world scientific news 114 (2018) 15-29...

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