Phenotypic expression of homozygous hemoglobin S in relation to β-globin haplotypes, glutathione S-transferase polymorphisms and detoxification enzymes

Sickle cell anemia (SCA) shows a pathophysiology that involves multiple changes in sickle cell erythrocytes, vaso-occlusive episodes, hemolysis, activation of inflammatory mediators, endothelial cell dysfunction, and oxidative stress. These events complicate treatment and culminate in the development of manifestations such as anemia, pain crises and multiorgan dysfunction. The aim of this study was to evaluate, in SCA patients, oxidative stress and antioxidant capacity markers, correlating them to treatment with hydroxyurea (HU), β-globin haplotypes and glutathione S-transferase polymorphisms (GSTT1, GSTM1 and GSTP1), in comparison to a control group (CG). The study groups were composed of 48 individuals without hemoglobinopathies (CG), SCA patients treated with HU [AF (+HU), N = 13] and untreated SCA patients [AF (-HU), N = 15], after informed consent. The groups were analyzed using cytological, electrophoretic, chromatographic and molecular methods and information from medical records. The GSTM1 and GSTT1 polymorphisms were determined by multiplex PCR, while the GSTP1 polymorphism by PCR-RFLP. Biochemical parameters were measured using spectrophotometric methods [TBARS, TEAC and catalase (CAT) and GST activities] and a chromatographic method [glutathione (GSH)]. The fetal Hb (Hb F) levels observed in the SCA (+HU) group (10.9%) confirmed the already well-described pharmacological effect of HU, but the SCA (-HU) group also had high Hb F levels (6.1%), which may have been influenced by genetic factors not targeted in this study. We found a higher frequency of the Bantu haplotype (48.2%), followed by the Benin (32.1%) and also Cameroon haplotypes, rare in our population, and 19.7% of atypical haplotypes. The presence of Bantu haplotype was related to higher lipid peroxidation levels in patients, but also, it conferred a differential response to HU treatment, raising Hb F levels in 52.6% (P = 0.03). The protective effect of Hb F was confirmed, because the increase in their levels resulted in a 41.3% decrease in lipid peroxidation levels (r = -0.74, P = 0.0156). The genotypic frequency of the GST polymorphisms observed was similar to that of other studies in the Brazilian population, and its association with biochemical markers revealed a significant difference only for the GSTP1 polymorphism, where patients with genotype V/V showed higher GSH and TEAC levels (P = 0.04 and P = 0.03, respectively) compared to patients with genotype I/I. The TBARS levels were about five to eight times higher in the SCA (+HU) and SCA (-HU) groups, respectively, compared to controls, and HU produced a 35.2% decrease in lipid peroxidation levels in the SCA (+HU) group (P < 0.0001). Moreover, the SCA (+HU) group showed higher TEAC levels when compared to CG (P = 0.002). We did not find any significant difference in GST activity between the groups studied (P = 0.76), but CAT activity was about 17 and 30% lower in SCA (+HU) and SCA (-HU) groups, respectively (P < 0.00001). Plasma GSH levels were ~2 times higher in SCA patients than in the control group (P = 0.0005) and showed a positive correlation with TBARS levels, confirming its antioxidant function. HU treatment contributed to higher CAT activity and TEAC levels and lower lipid peroxidation, and its pharmacological effect showed a “haplotype-dependent” response. These findings may contribute to elucidating the potential of HU in ameliorating oxidative stress in SCA subjects.

Phylogeography of the freshwater red alga Sirodotia (Batrachospermales, Rhodophyta) in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of training status and eNOS haplotypes on plasma nitrite concentrations in normotensive older adults: a hypothesis-generating study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of NAMPT polymorphisms and haplotypes on circulating visfatin/NAMPT levels in hypertensive disorders of pregnancy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genetic structure and historical diversification of catfish Brachyplatystoma platynemum (Siluriformes: Pimelodidae) in the Amazon basin with implications for its conservation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Study of lipid metabolism-related genes as candidate genes of sexual precocity in Nellore cattle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Low levels of taurine introgression in the current Brazilian Nelore and Gir indicine cattle populations

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Prospection of genomic regions divergently selected in cutting line of quarter horses in relation to racing line

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genome-wide association study and ancestral origins of the slick-hair coat in tropically adapted cattle

The slick hair coat (SLICK) is a dominantly inherited trait typically associated with tropically adapted cattle that are from Criollo descent through Spanish colonization of cattle into the New World. The trait is of interest relative to climate change, due to its association with improved thermo-tolerance and subsequent increased productivity. Previous studies localized the SLICK locus to a 4 cM region on chromosome (BTA) 20 and identified signatures of selection in this region derived from Senepol cattle. The current study compares three slick-haired Criollo-derived breeds including Senepol, Carora, and Romosinuano and three additional slick-haired cross-bred lineages to non-slick ancestral breeds. Genome-wide association (GWA), haplotype analysis, signatures of selection, runs of homozygosity (ROH), and identity by state (IBS) calculations were used to identify a 0.8 Mb (37.7-38.5 Mb) consensus region for the SLICK locus on BTA20 in which contains SKP2 and SPEF2 as possible candidate genes. Three specific haplotype patterns are identified in slick individuals, all with zero frequency in non-slick individuals. Admixture analysis identified common genetic patterns between the three slick breeds at the SLICK locus. Principal component analysis (PCA) and admixture results show Senepol and Romosinuano sharing a higher degree of genetic similarity to one another with a much lesser degree of similarity to Carora. Variation in GWA, haplotype analysis, and IBS calculations with accompanying population structure information supports potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus.

HLA-E coding and 3' untranslated region variability determined by next-generation sequencing in two West-African population samples

HLA-E is a non-classical Human Leucocyte Antigen class I gene with immunomodulatory properties. Whereas HLA-E expression usually occurs at low levels, it is widely distributed amongst human tissues, has the ability to bind self and non-self antigens and to interact with NK cells and T lymphocytes, being important for immunosurveillance and also for fighting against infections. HLA-E is usually the most conserved locus among all class I genes. However, most of the previous studies evaluating HLA-E variability sequenced only a few exons or genotyped known polymorphisms. Here we report a strategy to evaluate HLA-E variability by next-generation sequencing (NGS) that might be used to other HLA loci and present the HLA-E haplotype diversity considering the segment encoding the entire HLA-E mRNA (including 5'UTR, introns and the 3'UTR) in two African population samples, Susu from Guinea-Conakry and Lobi from Burkina Faso. Our results indicate that (a) the HLA-E gene is indeed conserved, encoding mainly two different protein molecules; (b) Africans do present several unknown HLA-E alleles presenting synonymous mutations; (c) the HLA-E 3'UTR is quite polymorphic and (d) haplotypes in the HLA-E 3'UTR are in close association with HLA-E coding alleles. NGS has proved to be an important tool on data generation for future studies evaluating variability in non-classical MHC genes.

Male-specific contributions to the Brazilian population of Espirito Santo

Y chromosome markers have been widely studied due to their various applications in the fields of forensic and evolutionary genetics. In this study, 35 Y-SNPs and 17 Y-STRs were genotyped in 253 males from the State of Espirito Santo, Brazil. A total of 18 haplogroups and 243 haplotypes were detected; the haplogroup and haplotype diversities were 0.7794 and 0.9997, respectively. Genetic distance analysis using the Y-STR data showed no statistically significant differences between Espirito Santo and other admixed populations from Brazil. The classification of paternal lineages based on haplogroups showed a predominant European contribution (85.88 %), followed by African (11.37 %) and Amerindian (2.75 %) contributions.

Análises genético-populacionais em arara-azul-grande (Anodorhynchus hyacinthinus) baseadas em marcadores mitocondriais: contribuições à conservação biológica da espécie

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Imputation of microsatellite alleles from dense SNP genotypes for parentage verification across multiple Bos taurus and Bos indicus breeds

To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ≤1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset.

Estrutura da população e epidemiologia de Moniliophthora roreri no Magdalena Medio Colombiano

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)