HLA‐F polymorphisms in a Euro‐Brazilian population from Southern Brazil

Abstract

HLA-F is a non-classical major histocompatibility complex (MHC) gene. It codes class Ib MHC molecules with restricted distribution and less nucleotide variations than MHC class Ia genes. Of the 22 alleles registered on the IMGT database only four alleles encode for proteins that differ in their primary structure. To estimate genotype and allele frequencies, this study targeted on known protein coding regions of the HLA-F gene. Genotyping was performed by Sequence Base Typing (SBT). The sample was composed by 199-unrelated bone marrow donors from the Brazilian Bone Marrow Donor Registry (REDOME), Euro-Brazilians, from Southern Brazil. About 1673 bp were analyzed. The most frequent allele was HLA-F*01:01 (87.19%), followed by HLA-F*01:03 (12.31%), HLA-F*01:02 (0.25%) and HLA-F*01:04 (0.25%). Significant linkage disequilibrium (LD) was verified between HLA-F and HLA classes I and II alleles. This is the first study regarding HLA-F polymorphisms in a Euro-Brazilian population contributing to the Southern Brazilian genetic characterization.

HLA-F coding and regulatory segments variability determined by massively parallel sequencing procedures in a Brazilian population sample

“…Considering the variable sites that were phased and included in the haplotype analysis (Tables 1 and 2), only four different HLA-F encoded molecules were found in the present sample, including F⁄01:01 (82.45%), F⁄01:03 (16.08%) and F⁄01:04 (1.28%), following the same pattern observed in China [59] and in Southern Brazil [61]. We did not detect the F⁄01:02 allele in the present sample, corroborating the former HLA-F study in Brazil [61]. In addition, a new HLA-F molecule (due to the presence of a novel non-synonymous mutation) was also detected in a single individual.…”

“…HLA-F variability has been minimally explored among human populations. Few studies have evaluated it, some of them using methodologies that detected only known variable sites [50,[57][58][59][60][61]. Altogether, these studies indicated that only two HLA-F protein molecules are mainly detected, named F⁄01:01 and F⁄01:03, with F⁄01:01 corresponding for more than 90% of the HLA-F encoded molecules.…”

“…Nevertheless, HLA-F variability has been poorly explored in worldwide populations. In fact, only one study sequenced the entire HLA-F segment in some cell lines [57], while the few remaining studies searched for variable sites that were already described at that moment [50,[58][59][60], or evaluated only a partial HLA-F coding sequence using sequencing procedures [61]. Thus, it is not clear whether HLA-F truly presents low diversity, or if it is a bias driven by its poor exploration.…”

Co-infecção Plasmodium falciparum e Schistosoma haematobium: papel dos genes HLA não-clássicos de classe I (HLA-G, -E e -F) na suscetibilidade à malária

“…The protein F*01:01 was observed in 77.63% of the individuals, accompanied by F*01:03 (19.41%) and F*01:02 (2.96%) (Table 15). These frequencies are closely similar to those reported in several studies, which mainly detected the two proteins (F*01:01 and F*01:03), for which F*01:01 is usually detected at higher frequency, and F*01:02, when detected, was always at low frequency (Pyo et al 2006;Moscoso et al 2007;Zhang et al 2012;Pan et al 2013;Manvailer et al 2014;Lima et al 2016). The presence of dinucleotide repeats at position +3097, as detected here (Table S3 in appendix III and Table 15) and in other studies (Auton et al 2015;Lima et al 2016), confirmed the existence of microsatellites and consequently the existence of new haplotypes harboring these microsatellites.…”

“…encode five full-length proteins (F*01:01, F*01:02, F*01:03, F*01:04 and F*01:05) (IPD-IMGT/HLA v.3.32.0, 2018-04-16), but only F*01:01 (82.45%) and F*01:03 (16.03%) are frequently observed in worldwide populations(Lima et al 2016). Some studies have genotyped only the well-described HLA-F polymorphisms in Korean and Chinese populations(Moscoso et al 2007;Kim et al 2011;Zhang et al 2012;Pan et al 2013); however, few reports are available regarding the nucleotide variability of HLA-F gene segments or of the entire gene region in Brazilians(Manvailer et al 2014;Lima et al 2016) and Asian, African…”