1. Next generation sequencing characterizes the extent of HLA diversity in an Argentinian registry population
- Author
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Elizabeth Enriquez, J. Gerfen, Michael Halagan, Jennifer Ng, M. B. Rodriguez Cardozo, D. Behm, Pablo E. Galarza, A. Lazaro, Lihua Hou, Carolyn Katovich Hurley, and Martin Maiers
- Subjects
0301 basic medicine ,Nonsynonymous substitution ,Sequence analysis ,Immunology ,Population ,Argentina ,Locus (genetics) ,Human leukocyte antigen ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,HLA Antigens ,Genetics ,Humans ,Immunology and Allergy ,Registries ,Allele ,education ,Allele frequency ,Alleles ,education.field_of_study ,Base Sequence ,Haplotype ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Exons ,Introns ,030104 developmental biology ,Haplotypes ,Genetic Loci ,030215 immunology - Abstract
Next generation DNA sequencing is used to determine the HLA-A, -B, -C, -DRB1, and -DQB1 assignments of 1472 unrelated volunteers for the unrelated donor registry in Argentina. The analysis characterized all HLA exons and introns for class I alleles; at least exons 2, 3 for HLA-DRB1; and exons 2 to 6 for HLA-DQB1. Of the distinct alleles present, there are 330 class I and 98 class II. The majority (~98%) of the cumulative allele frequency at each locus is contributed by alleles that appear at a frequency of at least 1 in 1000. Fourteen (18.2%) of the 77 novel class I and II alleles carry nonsynonymous variation within their exons; 52 (75.4%) class I novel alleles carry only single, apparently random, nucleotide variation within their introns/untranslated regions. Alleles encoding protein variation not usually detected by typing focused only on the exons encoding the antigen recognition domain are 1.0% of the class I assignments and 7.3% of the class II assignments (predominantly DQB1*02:02:01, DQB1*03:19:01, and DRB1*14:54:01). Updates to the common and well documented list of alleles include 10 alleles previously thought to be uncommon but that are found at least 30 times. Five locus haplotypes estimated using the expectation-maximization algorithm as present 3 or more times total 187. While the known HLA diversity continues to increase, the conservation of known allele sequences is remarkable. Overall, the HLA diversity observed in the Argentinian population reflects its European and Native American ancestry.
- Published
- 2018