The HLA‐A, ‐B and ‐DRB1 polymorphism in a large dataset of South Brazil bone marrow donors from Rio Grande do Sul

Abstract

Human leukocyte antigen (HLA) genes are very informative in population genetics studies and their variability has been widely used to reconstruct the history of geographic and/or demographic expansions of human populations. The characterization of HLA diversity at the population level is also fundamental in clinical studies, particularly for bone marrow transplantation programs. In this study, we investigated the HLA molecular variation in Rio Grande do Sul, South Brazil, in order to identify possible regional differences across this state. More than 97,000 bone marrow donors were typed at the HLA- A, -B and -DRB1 loci and analyzed by considering two kinds of subdivisions based on both self-identified ethnicity and place of residence: (a) the official geographic subdivision defined by the Brazilian Institute of Geography and Statistics and (b) known information about the colonization history of the state. HLA allele and haplotype frequencies were estimated and compared among the defined subgroups. The results indicate a lack of correlation between genetic variation and geography and thus no clear HLA genetic structure based on geographic criteria. On the other hand, major differences were observed regarding ethnicity. In addition, local populations from Rio Grande do Sul were found to be genetically similar to their corresponding parental European populations from Germany, Italy and Portugal, as documented by historical data. Overall, this study provides a thorough characterization of the HLA genetic variation in Rio Grande do Sul and a better understanding of its demographic history, being most useful for the development of more efficient strategies in bone marrow donors' recruitment.

High‐resolution characterization of 12 classical and non‐classical HLA loci in Southern Brazilians

“…In addition, these data may improve donor‐recipient matching, as an increasing number of studies show that HLA genes other than the most studied HLA‐A , ‐B , ‐C , ‐DQB1 , and ‐DRB1 also impact hematopoietic stem cell and organ transplantation . Our results reinforce allelic and haplotypic similarities between the population from Curitiba and European populations, which corroborates previous studies that analyzed Euro‐descendants from Southern Brazil …”

HLA diversity in Brazil

“…We found that HLA itself is a better predictor of ancestry than the self‐declaration based on skin color, corroborating findings from other studies with other genetic markers . In 2017, in an extensive study using more than 97 000 voluntary bone marrow donors across the state, we tested whether there was population structure according to the state's political division . The results indicated that there is no population structure according to this division, but there is genetic (HLA) structure reflecting the cultural regions associated to the colonization history of Rio Grande do Sul .…”

“…For a broader view of the HLA in Brazilian populations we gathered data from all studies that presented allele frequencies genotyped by molecular methods for HLA-A, HLA-B and HLA-DRB1 included in this revision and we calculated the Prevosti's genetic distance as described elsewhere. 43 Studies based on patients with autoimmune diseases were not included to avoid bias. The allele frequencies used were at first field level (low resolution) and the results were plotted in multidimensional scaling (MDS) (Figure 2).…”

“…43 The results indicated that there is no population structure according to this division, but there is genetic (HLA) structure reflecting the cultural regions associated to the colonization history of Rio Grande do Sul. 43 Recently, in 2018, we used georeferencing geographic information system (GIS) tools from more than 86 000 voluntary bone marrow donors from 120 cities across the state. PCA data were used to calculate the synthetic genetic structure and plotted through GIS, resulting in a map very similar to the cultural regions of the state.…”

“…In 2017, in an extensive study using more than 97 000 voluntary bone marrow donors across the state, we tested whether there was population structure according to the state's political division . The results indicated that there is no population structure according to this division, but there is genetic (HLA) structure reflecting the cultural regions associated to the colonization history of Rio Grande do Sul . Recently, in 2018, we used georeferencing geographic information system (GIS) tools from more than 86 000 voluntary bone marrow donors from 120 cities across the state.…”