Frequency and parameters of linkage disequilibrium of the two-locus HLA-B~MICA haplotypes in russians from chelyabinsk region

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Abstract

MICA gene is located in the MHC region on chromosome 6p21.33, mapped ca. 46.4 kb centromeric to the HLA-B gene, being in strict linkage disequilibrium with MHC class I region. The sufficient polymorphism of human MICA gene and its location at the HLA region makes it a likely candidate locus for additional histocompatibility testing. The data on distribution of two-locus HLA-B~MICA haplotypes enable us to obtain information about the level of mismatches in the MICA locus when selecting suitable donor-recipient pair by convential HLA loci for unrelated hematopoietic stem cell transplantation. We have performed immunogenetic typing of 100 donors of Russian Nationality from the Register of Stem Cell Donors at Chelyabinsk Regional Blood Bank. MICA genotyping was carried out by PCR tests with sequence-specific primers at basic resolution. Typing of the classical HLA-B locus was carried out by the NGS method using MiSeq instrument using a MiSeq v2 reagent kit (Illumina). Linkage disequilibrium indices D, D`, p, and the frequency of two-locus HLA-B~MICA haplotypes were calculated using Arlequin 3.5 software. As a result of this study, the main parameters of linkage disequilibrium and the frequency of two-locus HLA-B~MICA haplotypes were established for Russians from the Chelyabinsk region. HLA-B allelic groups have been identified that form stable pairs with specific MICA allelic variants (HLA-B*B*07, B*08, B*13, B*14, B* 27, B*37, B*38, B*47, B *48, B*49, B*50, B*52, B*55, B*56, B*57). Moreover, we have revealed HLA-B allelic groups forming highly variable HLA-B~MICA haplotypes (HLA-B*15, B*18, B*35, B*39, B*40, B*41, B*44 and B*51) with increased risk of mismatch for MICA genes. These results could be used in clinical practice in order to assess probability of the donor/recipient mismatch for non-classic MICA locus when selecting potential stem cell donors for hematological patients by HLA testing of classical loci. Moreover, these data could be demanded in population genetics.

About the authors

Mikhail N. Vavilov

Chelyabinsk State University; Chelyabinsk Regional Blood Transfusion Station

Author for correspondence.
Email: vavlakhim@mail.ru
SPIN-code: 8639-2391

Postgraduate Student, Department of Microbiology, Immunology and General Biology, Faculty of Biology, Biologist, Laboratory of Immunological Testing

Russian Federation, apt 48, 7a, Marchenko str., Chelyabinsk, 454085; Chelyabinsk

Tatiana A. Suslova

Chelyabinsk State University; Chelyabinsk Regional Blood Transfusion Station

Email: tatiana.suslova.hla@gmail.com

PhD (Medicine), Associate Professor, Department of Microbiology, Immunology and General Biology, Faculty of Biology, Head, Laboratory of Immunological Testing

Russian Federation, Chelyabinsk; Chelyabinsk

Aleksandra L. Burmistrova

Chelyabinsk State University

Email: burmal@csu.ru

PhD, MD (Medicine), Professor, Head, Department of Microbiology, Immunology and General Biology, Faculty of Biology

Russian Federation, Chelyabinsk

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2. Figure 1. Multivariate scaling in two dimensions based on the frequencies of two-locus HLA-B~MICA haplotypes of 23 populations. Note. The diagram was built in the PAST program (version 2.17) based on the frequencies of the two-locus HLA-B~MICA haplotypes of 23 populations, using the method of Multidimensional scaling (MDS). Stress value = 0.1994 (from 0.4 – low to 0.0 – ideal). World populations included in the comparative study (in parentheses are the sample size, the author of the study and the year): “Africa”: Nigeria Efik (32, Tian W., 2002), Nigeria Y. Igbo (46, Tian W., 2002), Nigeria Yu Yoruba (74, Tian W., 2002), US African American 1 (201, Zhang Y., 2002), US African American 2 (39, Tian W., 2002), US Boston African American (60, Tian W., 2002); “Europe”: US Caucasians 1 (242, Petersdorf E.W., 1998), US Caucasians 2 (103, Zhang Y., 2000), Morocco Metalsa (82, Piancatelli D., 2001), Spain Mallorca (165, Cambra A., 2008 ), Spain Murcia (154, Lucas D., 2007), Spain Mallorca Chueta (95, Cambra A., 2009); “Asia”: Brazil Japanese (190, de Alencar J.B., 2017), China Baotou Han (104, Tian W., 2009), China Zhejiang Han (100, Zhu F., 2008), South Korea (199, Pyo C.-W., 2003), South Korea, Seoul (139, Sohn Y.-H., 2009), Northeast Thailand (255, Romphruk A.V., 2000); “Others”: Argentina Formosa Toba (94, Zhang Y., 2002), Argentina Formosa Vichi (42, Zhang Y., 2002), Brazil Parana Mixed (201, Visentainer J.E.L., 2011), Brazil São Paulo Mixed (200, Marin M.L.C., 2001)

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Copyright (c) 2022 Vavilov M.N., Suslova T.A., Burmistrova A.L.

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