Although autologous induced pluripotent stem cells (iPSCs) can potentially be useful for treating patients without immune rejection, in reality it will be extremely expensive and labor-intensive to make iPSCs to realize personalized medicine. An alternative approach is to make use of human leukocyte antigen (HLA) haplotype homozygous donors to provide HLA matched iPSC products to significant numbers of patients. To establish a haplobank of iPSCs, we repurposed the cord blood bank by screening ∼4,200 high resolution HLA typed cord blood samples, and selected those homozygous for the 10 most frequent HLA-A,-B,-DRB1 haplotypes in the Korean population. Following the generation of 10 iPSC lines, we conducted a comprehensive characterization, including morphology, expression of pluripotent markers and cell surface antigens, three-germ layer formation, vector clearance, mycoplasma/microbiological/viral contamination, endotoxin, and short tandem repeat (STR) assays. Various genomic analyses using microarray and comparative genomic hybridization (aCGH)-based single nucleotide polymorphism (SNP) and copy number variation (CNV) were also conducted. These 10 HLA-homozygous iPSC lines match 41.07% of the Korean population. Comparative analysis of HLA population data shows that they are also of use in other Asian populations, such as Japan, with some limited utility in ethnically diverse populations, such as the UK. Taken together, the generation of the 10 most frequent Korean HLA-homozygous iPSC lines serves as a useful pointer for the development of optimal methods for iPSC generation and quality control and indicates the benefits and limitations of collaborative HLA driven selection of donors for future stocking of worldwide iPSC haplobanks. Stem Cells 2018;36:1552-1566.

While the success of allogeneic stem cell transplantation depends on a high degree of HLA compatibility between donor and patient, finding a suitable donor remains challenging due to the hyperpolymorphic nature of HLA genes. We calculated high-resolution allele, haplotype and phenotype frequencies for HLA-A,-C,-B,-DRB1 and-DQB1 for 10 subpopulations of the Anthony Nolan (AN) register using an in-house expectation-maximisation (EM) algorithm run on mixed resolution HLA data, covering 676 155 individuals. Sample sizes range from 599 410 for British/Irish North West European (BINWE) individuals, the largest subpopulation in the United Kingdom to 1105 for the British Bangladeshi population. Calculation of genetic distance between the subpopulations based on haplotype frequencies shows three broad clusters, each following a major continental group: European, African and Asian. We further analysed the HLA haplotype and phenotype diversity of each subpopulation, and found that 35.52% of BINWE individuals ranging to 98.34% of Middle Eastern individuals on the register had a unique phenotype within their subpopulation. These analyses and the allele, haplotype and phenotype frequency data of the subpopulation on the AN register are a valuable resource in understanding the HLA diversity in the United Kingdom and can be used to improve the accuracy of match likelihoods and to inform future donor recruitment strategies.

The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high-resolution HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub-Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub-Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro-descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high-resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation.