HLA Haplotypes In 250 Families: The Baylor Laboratory Results And A Perspective On A Core NGS Testing Model For The 17th International HLA And Immunogenetics Workshop.

Since their inception, the International HLA & Immunogenetics Workshops (IHIW) served as a collaborative platform for exchange of specimens, reference materials, experiences and best practices. In this report we present a subset of the results of human leukocyte antigen (HLA) haplotypes in families tested by next generation sequencing (NGS) under the 17th IHIW. We characterized 961 haplotypes in 921 subjects belonging to 250 families from 8 countries (Argentina, Austria, Egypt, Jamaica, Germany, Greece, Kuwait, and Switzerland). These samples were tested in a single core laboratory in a high throughput fashion using 6 different reagents/software platforms. Families tested included patients evaluated clinically as transplant recipients (kidney and hematopoietic cell transplant) and their respective family members. We identified 486 HLA alleles at the following loci HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, -DPB1 (77, 115, 68, 69, 10, 6, 4, 44, 31, 20 and 42 alleles, respectively). We also identified nine novel alleles with polymorphisms in coding regions. This approach of testing samples from multiple laboratories across the world in different stages of technology implementation in a single core laboratory may be useful for future international workshops. Although data presented may not be reflective of allele and haplotype frequencies in the countries to which the families belong, they represent an extensive collection of 3rd and 4th field resolution level 11-locus haplotype associations of 486 alleles identified in families from 8 countries.

Next-generation sequencing characterization of HLA in multi-generation families of Kuwaiti descent.

The frequency of HLA genes in one population may not accurately represent frequencies in other populations. In this study, we characterized extended human leukocyte antigen (HLA) haplotypes in several families of Kuwaiti descent by high-resolution typing using next-generation technology. A total 81 members (including patients and related donors) from 21 families were enrolled. No haplotypes were shared among multiple families. Of 77 haplotypes identified, 23 were not listed in the HaploStats database. Two haplotypes were most common in African Americans, six in Asian Pacific Islanders, three in Caucasians, three in Hispanics, and three in Native Americans. The remaining identified haplotypes were not among the most common 200 HLA haplotypes in any of the five major populations. This cohort had 202 (19%) unique alleles, including 20 rare alleles, 16 very rare alleles, and 2 novel ones. Furthermore, no frequency data were available for 30% (23/77) of the observed haplotypes, and 6% (3/49) of B ∼ C blocks identified were not available in the HaploStats database. Kuwaiti individuals carry unique HLA haplotypes that are not shared by the majority of individuals historically reported to the US National Marrow Donor Program registry.