DC-SIGN (CD209) gene promoter polymorphisms in a Brazilian population and their association with human T-cell lymphotropic virus type 1 infection

This study evaluated four polymorphisms located in the DC-SIGN (CD209) gene promoter region (positions −336, −332 −201 and −139) in DNA samples from four Brazilian ethnic groups (Caucasians, Afro-Brazilian, Asians and Amerindians) to establish the population distribution of these single-nucleotide polymorphisms (SNPs) and correlated DC-SIGN polymorphisms and infection in samples from human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals. To identify CD209 SNPs, 452 bp of the CD209 promoter region were sequenced and the genotype and allelic frequencies were evaluated. This is the first study to show genetic polymorphism in the CD209 gene in distinct Brazilian ethnic groups with the distribution of allelic and genotypic frequency. The results showed that −336A and −139A SNPs were quite common in Asians and that the −201T allele was not observed in Caucasians, Asians or Amerindians. No significant differences were observed between individuals with HTLV-1 disease and asymptomatic patients. However, the −336A variant was more frequent in HTLV-1-infected patients [HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 80 %; healthy asymptomatic HTLV-1 carriers, 90 %] than in the control group (70 %) [P=0.0197, odds ratio (OR)=2.511, 95 % confidence interval (CI)=1.218–5.179). In addition, the −139A allele was found to be associated with protection against HTLV-1 infection (P=0.0037, OR=0.3758, 95 % CI=0.1954–0.7229) when the HTLV-1-infected patients as a whole were compared with the healthy-control group. These observations suggest that the −139A allele may be associated with HTLV-1 infection, although no significant association was observed among asymptomatic and HAM/TSP patients. In conclusion, the variation observed in SNPs −336 and −139 indicates that this lectin may be of crucial importance in the susceptibility/transmission of HTLV-1 infections

Transcriptional and Posttranscriptional Regulations of the HLA-G Gene

HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-gamma and NF-kappa B, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3' untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3' UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region

Evaluation of MC1R high-throughput nucleotide sequencing data generated by the 1000 Genomes Project

Abstract The advent of next-generation sequencing allows simultaneous processing of several genomic regions/individuals, increasing the availability and accuracy of whole-genome data. However, these new approaches may present some errors and bias due to alignment, genotype calling, and imputation methods. Despite these flaws, data obtained by next-generation sequencing can be valuable for population and evolutionary studies of specific genes, such as genes related to how pigmentation evolved among populations, one of the main topics in human evolutionary biology. Melanocortin-1 receptor (MC1R) is one of the most studied genes involved in pigmentation variation. As MC1R has already been suggested to affect melanogenesis and increase risk of developing melanoma, it constitutes one of the best models to understand how natural selection acts on pigmentation. Here we employed a locally developed pipeline to obtain genotype and haplotype data for MC1R from the raw sequencing data provided by the 1000 Genomes FTP site. We also compared such genotype data to Phase 3 VCF to evaluate its quality and discover any polymorphic sites that may have been overlooked. In conclusion, either the VCF file or one of the presently described pipelines could be used to obtain reliable and accurate genotype calling from the 1000 Genomes Phase 3 data

A nonsynonymous mutation at HLA-E defines the new E*01:06 allele in Brazilian individuals

We report a novel nonclassical class I HLA-E*01:06 allele observed in Brazilian individuals

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3′UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.Genes and Immunity advance online publication, 3 October 2013; doi:10.1038/gene.2013.47

Detecção molecular do rearranjo Line-1 /c-Myc em tumores venéreos transmissíveis caninos espôntaneos

Transmissible venereal tumor (TVT) is a neoplasia that develops naturally in dogs. It can be easily transplanted, which demonstrates its ability to spread from animal to animal. Since the Linr-1/c-MYC rearrangement in TVT cells had not been studied at the Veterinary Hospital of the Veterinary School, Unesp in Botucatu, SP, this study aimed to detect this genetic alteration specific to this kind of tumor by means of the polymerase chain reaction (PCR). Twenty dogs with cytological diagnosis of TVT were used. Samples of neoplastic cells were collected to determine the presence of the Line-1/c-MYC marker. The rearrangement characterized by 340bp amplicons did not vary, in agreement with previous studies using the same methodology. This contributed to a more precise identification of persistent tumor cells in cases in which gross or microscopical detection was not possible.El tumor venéreo transmisible (TVT) es una neoplasia que se desarrolla en perros en condiciones naturales. Debido a que la disposición del rearreglo Line-1/c-MYC no ha sido estudiada en las células de TVT en nuestra institución, Unesp en Botucatu, SP, este estudio tuvo como objetivo detectar su localización por medio de la reacción en cadena de la polimerasa (PCR), donde esta alteración es específica de este tumor. Fueron utilizados veinte animales con diagnóstico citológico de TVT. Posteriormente las células tumorales fueron colectadas para detectar la presencia del marcador Line-1/c-MYC. La disposición caracterizada por el tamaño de 340pb no tuvo variación en las muestras, coincidiendo con resultados de otros estudios, considerándose satisfactorio desde el punto de vista clínico y diagnóstico, contribuyendo en la identificación más precisa de las células neoplásicas persistentes, donde las mismas no serían visibles macro y microscópicamente, hecho que podría provocar la recurrencia del tumor en cuestión.O tumor venéreo transmissível (TVT) é uma neoplasia que se desenvolve em condições naturais no cão. É de fácil transplantação, demonstrando a capacidade de transmissão de um animal para outro. Pelo fato de o rearranjo Line-1/c-MYC ainda não ter sido estudado nas células do TVT no Hospital Veterinário da FMVZ, Unesp, campus de Botucatu, SP, este estudo teve por objetivo detectar o rearranjo, uma alteração genética específica desse tumor, por meio da reação em cadeia da polimerase (PCR). Para tanto, foram utilizados vinte cães com diagnóstico citológico de TVT. Amostras das células tumorais foram colhidas para se detectar a presença do marcador Line-1/c-MYC. O rearranjo caracterizado por amplicons de 340pb de tamanho não variou nas amostras, em concordância com descrições anteriores, contribuindo para a identificação mais precisa das células neoplásicas persistentes em casos nos quais o neoplasma não seja macroscópica ou microscopicamente detectável, o que poderia ocasionar a recorrência do tumor em questão