The distribution of HLA haplotypes in the ethnic groups that make up the Brazilian Bone Marrow Volunteer Donor Registry (REDOME)

Abstract

The Registries of Bone Marrow Donors around the world include more than 30 million volunteer donors from 57 different countries, and were responsible for over 17,000 hematopoietic stem cell transplants in 2016. The Brazilian Bone Marrow Volunteer Donor Registry (REDOME) was established in 1993 and is the third largest registry in the world with more than 4.3 million donors. We characterized HLA allele and haplotypes frequencies from REDOME comparing them with the donor self-reported race group classification. Five-locus haplotype frequencies (A~C~B~DRB1~DQB1) were estimated for each of the six race groups, resolving phase and allelic ambiguity using the expectation-maximization (EM) algorithm. The top 100 haplotypes in the race groups were separated into eight clusters of haplotypes, based on haplotype similarity, using CLUTO. We present HLA allele and haplotype frequency data from six race groups from 2,938,259 individuals from REDOME. The most frequent haplotype was the same for all groups: A*01:01g~C*07:01g~B*08:01g~DRB1*03:01g~DQB1*02:01g. Some frequent haplotypes such as A*02:01g~C*16:01g~B*44:03~DRB1*07:01g~DQB1*02:01g was not found in people with Preta (Sub-Saharan African descent). A cluster including Branca (European) and Parda or non-informed (admixed) could be distinguished from both Preta (SubSaharan) and Indígena (Amerindian) groups, and from the Amarela (Asian) ones, which clustered with their original population. These results have implications on cross-population matching and can help in donor searches and population-based recruitment strategies.

HLA diversity in Brazil

“…Self‐declared Yellow and the population of the North were closer to the Mexican population, indicating a Native American component, although the self‐declared Indigenous population was not close to the Mexican population on the plot presented in the study . Recently, Halagan et al conducted a new study with the entire database of voluntary bone marrow donors in Brazil including medium‐ and high‐resolution genotypes and including HLA‐C and ‐DQB1. Brazilian populations, divided according to self‐declaration of skin color, were compared to the populations present in the NMDP (National Marrow Donor Program, USA).…”

Characterization of the first HLA‐B*15:31 variant, B*15:31:01:02, found in a Brazilian individual

“…1 In Rio de Janeiro, Brazil, the antigen frequency for the HLA-B*15 allele is 9.1%. 2 In this report, we describe the full sequence of the first HLA-B*15:31:01 variant, called HLA-B*15:31:01:02, found in a Brazilian male bone marrow donor, which was identified using the nextgeneration sequencing (NGS) typing method. The sequence of the novel allele has been submitted to GenBank with accession number MN208453 and to the IPD-IMGT/HLA Database with submission number HWS10055921.…”

Characterization of three novel HLA‐DQA1*03:03:01 variants, identified in Brazilian individuals

“…1 In Brazil, the antigen frequency for the HLA-DQA1*03 allele is 16.4%. 2 In this report, we describe the full sequence of three HLA-DQA1*03:03:01 variants, now named HLA-DQA1*03:03:01:08, HLA-DQA1*03:03:01:09, and HLA-DQA1*03:03:01:10, identified in three distinct Brazilian female bone marrow donors, which were identified using the next-generation sequencing (NGS) typing method. The sequences of the novel alleles have been submitted to GenBank with accession numbers MN153779, MN153780, and MN153781, respectively, and to the IPD-IMGT/HLA Database with submission numbers HWS10055627, HWS10055639, and HWS10055641, respectively.…”