Next generation sequencing characterizes the extent of HLA diversity in an Argentinian registry population.

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.

Four-locus high-resolution HLA typing in a sample of Mexican Americans.

Mexicans are the most common minority population of the United States. From a sample of 553 bone marrow donor registrants of self-described Mexican ancestry, human leukocyte antigen (HLA) loci A, C, B and DRB1 were typed by high resolution sequence based typing (SBT) methods. A total of 47, 34, 76 and 46 distinct alleles at A, C, B and DRB1 respectively were identified, including 3 new alleles. The four-locus haplotype frequency distribution was extremely skewed with only 53.9% of 1106 chromosomes present with more than one estimated copy. Haplotypes of Native American origin were identified. These data form an initial basis for determining the requirements for an adequate donor pool for stem cell transplantation in this population.