Fabreti-Oliveira R A, Nascimento E, Fonseca C G, Santos M A
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento da Ciência da Computação, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; IMUNOLAB - Laboratório de Histocompatibilidade, Imunogenética e Imunologia de Transplantes, Belo Horizonte, MG, Brazil.
Tissue Antigens. 2014 Aug;84(2):187-97. doi: 10.1111/tan.12352. Epub 2014 Apr 12.
The aim of this study was to investigate the human leukocyte antigen (HLA) molecular variation across the Brazilian population in order to determine possible regional differences, which would be highly relevant to optimizing donor recruitment strategies in hematopoietic stem cell transplantation (HSCT) and understanding the population genetic background of this heterogeneous country. HLA data of 551 HSCT donors from five Brazilian regions were characterized by high-resolution DNA alleles at the HLA-A, -B, -C, -DRB1 and -DQB1 loci and compared with other populations in Brazil and worldwide populations. Allele and haplotype frequencies were estimated. The analysis was performed to assess Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) among different loci in each recruitment center. Genetic variation was explored through genetic distance analyzed by using a new algorithm based on linear algebra, taking into account geographic regions of Brazil. The results indicated a heterogeneous genetic composition of the Brazilian population, such that HLA allele and haplotype frequencies exhibit different distributions among Brazilian regions, which has important implications for donor matching. In addition, a pronounced differentiation was observed by the absence of clustering of the regional populations in the reduced-dimension space. These data may be useful for increasing donor recruitment with more genetic representativeness in the Brazilian Volunteer Bone Marrow Donors Registry (REDOME).
本研究的目的是调查巴西人群中的人类白细胞抗原（HLA）分子变异，以确定可能存在的区域差异，这对于优化造血干细胞移植（HSCT）中的供体招募策略以及了解这个多元化国家的群体遗传背景具有高度相关性。来自巴西五个地区的551名HSCT供体的HLA数据通过HLA-A、-B、-C、-DRB1和-DQB1位点的高分辨率DNA等位基因进行表征，并与巴西的其他人群以及全球人群进行比较。估计了等位基因和单倍型频率。进行分析以评估每个招募中心不同位点之间的哈迪-温伯格平衡（HWE）和连锁不平衡（LD）。通过使用基于线性代数的新算法分析遗传距离来探索遗传变异，同时考虑巴西的地理区域。结果表明巴西人群的遗传组成具有异质性，使得HLA等位基因和单倍型频率在巴西各地区呈现不同分布，这对供体匹配具有重要意义。此外，在降维空间中区域人群未聚类，观察到明显的分化。这些数据可能有助于在巴西志愿骨髓捐献者登记处（REDOME）增加具有更多遗传代表性的供体招募。
