Single Haplotype Admixture Models Using Large Scale HLA Genotype Frequencies to Reproduce Human Admixture

Overview

Journal Immunogenetics

Specialties Allergy & Immunology
Genetics

Date 2019 Nov 20

PMID 31741008

Citations 1

Authors

Alexandra Litinsky Simanovsky

Abeer Madbouly

Michael Halagan

Martin Maiers

Yoram Louzoun

Affiliations

Soon will be listed here.

Abstract

The human leukocyte antigen (HLA) is the most polymorphic region in humans. Anthropologists use HLA to trace populations' migration and evolution. However, recent admixture between populations can mask the ancestral haplotype frequency distribution. We present a statistical method based on high-resolution HLA haplotype frequencies to resolve population admixture using a non-negative matrix factorization formalism and validated using haplotype frequencies from 56 world populations. The result is a minimal set of source components (SCs) decoding roughly 90% of the total variance in the studied admixtures. These SCs agree with the geographical distribution, phylogenies, and recent admixture events of the studied groups. With the growing population of multi-ethnic individuals, or individuals that do not report race/ethnic information, the HLA matching process for stem-cell and solid organ transplants is becoming more challenging. The presented algorithm provides a framework that facilitates the breakdown of highly admixed populations into SCs, which can be used to better match the rapidly growing population of multi-ethnic individuals worldwide.

Citing Articles

Influence of HLA Class II Polymorphism on Predicted Cellular Immunity Against SARS-CoV-2 at the Population and Individual Level.

Copley H, Gragert L, Leach A, Kosmoliaptsis V Front Immunol. 2021; 12:669357.

PMID: 34349756 PMC: 8327207. DOI: 10.3389/fimmu.2021.669357.

References

Porras-Hurtado L, Ruiz Y, Santos C, Phillips C, Carracedo A, Lareu M . An overview of STRUCTURE: applications, parameter settings, and supporting software. Front Genet. 2013; 4:98. PMC: 3665925. DOI: 10.3389/fgene.2013.00098. View

Bryc K, Durand E, Macpherson J, Reich D, Mountain J . The genetic ancestry of African Americans, Latinos, and European Americans across the United States. Am J Hum Genet. 2014; 96(1):37-53. PMC: 4289685. DOI: 10.1016/j.ajhg.2014.11.010. View

Malaspinas A, Westaway M, Muller C, Sousa V, Lao O, Alves I . A genomic history of Aboriginal Australia. Nature. 2016; 538(7624):207-214. PMC: 7617037. DOI: 10.1038/nature18299. View

Voight B, Kudaravalli S, Wen X, Pritchard J . A map of recent positive selection in the human genome. PLoS Biol. 2006; 4(3):e72. PMC: 1382018. DOI: 10.1371/journal.pbio.0040072. View

Slater N, Louzoun Y, Gragert L, Maiers M, Chatterjee A, Albrecht M . Power laws for heavy-tailed distributions: modeling allele and haplotype diversity for the national marrow donor program. PLoS Comput Biol. 2015; 11(4):e1004204. PMC: 4406525. DOI: 10.1371/journal.pcbi.1004204. View

Traherne J . Human MHC architecture and evolution: implications for disease association studies. Int J Immunogenet. 2008; 35(3):179-92. PMC: 2408657. DOI: 10.1111/j.1744-313X.2008.00765.x. View

Manor S, Halagan M, Shriki N, Yaniv I, Zisser B, Maiers M . High-resolution HLA A∼B∼DRB1 haplotype frequencies from the Ezer Mizion Bone Marrow Donor Registry in Israel. Hum Immunol. 2016; 77(12):1114-1119. DOI: 10.1016/j.humimm.2016.09.004. View

Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R . HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014; 371(4):339-48. PMC: 5965695. DOI: 10.1056/NEJMsa1311707. View

Sanchez-Mazas A, Thorsby E . HLA in anthropology: the enigma of Easter Island. Clin Transpl. 2014; :167-73. View

10.

McEvoy B, Lind J, Wang E, Moyzis R, Visscher P, van Holst Pellekaan S . Whole-genome genetic diversity in a sample of Australians with deep Aboriginal ancestry. Am J Hum Genet. 2010; 87(2):297-305. PMC: 2917718. DOI: 10.1016/j.ajhg.2010.07.008. View

11.

Behar D, Yunusbayev B, Metspalu M, Metspalu E, Rosset S, Parik J . The genome-wide structure of the Jewish people. Nature. 2010; 466(7303):238-42. DOI: 10.1038/nature09103. View

12.

Chua E, Kennedy M . Current State and Future Prospects of Direct-to-Consumer Pharmacogenetics. Front Pharmacol. 2012; 3:152. PMC: 3422723. DOI: 10.3389/fphar.2012.00152. View

13.

Gragert L, Fingerson S, Albrecht M, Maiers M, Kalaycio M, Hill B . Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations. Blood. 2014; 124(17):2657-65. PMC: 4208281. DOI: 10.1182/blood-2014-02-558767. View

14.

Wang S, Lewis C, Jakobsson M, Ramachandran S, Ray N, Bedoya G . Genetic variation and population structure in native Americans. PLoS Genet. 2007; 3(11):e185. PMC: 2082466. DOI: 10.1371/journal.pgen.0030185. View

15.

Maiers M, Halagan M, Joshi S, Ballal H, Jagannatthan L, Damodar S . HLA match likelihoods for Indian patients seeking unrelated donor transplantation grafts: a population-based study. Lancet Haematol. 2016; 1(2):e57-63. DOI: 10.1016/S2352-3026(14)70021-3. View

16.

Verdu P, Pemberton T, Laurent R, Kemp B, Gonzalez-Oliver A, Gorodezky C . Patterns of admixture and population structure in native populations of Northwest North America. PLoS Genet. 2014; 10(8):e1004530. PMC: 4133047. DOI: 10.1371/journal.pgen.1004530. View

17.

Robinson J, Halliwell J, Hayhurst J, Flicek P, Parham P, Marsh S . The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2014; 43(Database issue):D423-31. PMC: 4383959. DOI: 10.1093/nar/gku1161. View

18.

Lobkovsky A, Levi L, Wolf Y, Maiers M, Gragert L, Alter I . Multiplicative fitness, rapid haplotype discovery, and fitness decay explain evolution of human MHC. Proc Natl Acad Sci U S A. 2019; 116(28):14098-14104. PMC: 6628782. DOI: 10.1073/pnas.1714436116. View

19.

Gragert L, Madbouly A, Freeman J, Maiers M . Six-locus high resolution HLA haplotype frequencies derived from mixed-resolution DNA typing for the entire US donor registry. Hum Immunol. 2013; 74(10):1313-20. DOI: 10.1016/j.humimm.2013.06.025. View

20.

Gough S, Simmonds M . The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. Curr Genomics. 2009; 8(7):453-65. PMC: 2647156. DOI: 10.2174/138920207783591690. View