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Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.
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Polimorfismo de Nucleotídeo Único , Autorrelato , Pigmentação da Pele , Humanos , Brasil , Pigmentação da Pele/genética , Masculino , Feminino , Adulto , População Branca/genética , População Urbana , População Negra/genética , Grupos Raciais/genética , Pessoa de Meia-Idade , Genética PopulacionalRESUMO
OBJECTIVE: Studies of Wnt variants-related to bone resorption in periodontitis are limited. The aim of this study was to establish the genotype and allele frequency of gene variants associated with the Wnt pathway in systemically healthy individuals with and without periodontitis (PD). MATERIALS AND METHODS: One hundred fifty-seven systemically healthy individuals were evaluated, 90 with PD and 67 without PD. Periodontal clinical indexes, serological and clinical indices of inflammation, and the following variants associated with the Wnt pathway: DKK, SOST, LRP5, and KREMEN were analyzed by high resolution melting and confirmed by Sanger sequencing. RESULTS: In the PD-free group, 67.2% of the individuals presented the variant for DKKrs1896367 (p = 0.008) and 82.6% had the variant for KREMEN rs132274 (p = 0.016). The heterozygous variant for the DKK rs1896367 polymorphism was associated with the absence of PD and lower severity OR: 0.33 (CI95% 0.15-0.70) and OR: 0.24 (CI95% 0.11-0.53), respectively. Similarly, KREMEN rs132274 was the homozygous variant associated with the absence of PD (OR: 0.33 (CI95% 0.13-0.88)). On the contrary, 85.6% of individuals with PD presented a variant for DKK rs1896368 (p = 0.042), all suffering severe forms of periodontitis. CONCLUSION: The presence of DKKrs1896367 and KREMENrs132274 variants in individuals without PD suggests that these single nucleotide polymorphisms could be protective factors for bone loss in PD. A very interesting finding is that the DKKrs1896368 variant was found in a high percentage of severe cases, suggesting that the presence of this variant may be related to the severe bone loss observed in PD.
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Doenças Periodontais , Periodontite , Humanos , Via de Sinalização Wnt/genética , Inflamação , Polimorfismo de Nucleotídeo Único , Periodontite/genéticaRESUMO
Uncovering causal relationships between exposures and outcomes can be difficult in observational studies because of the potential for confounding and reverse causation to produce biased estimates. Conversely, randomized controlled trials (RCTs) provide the strongest evidence for causality but they are not always feasible. Mendelian randomization (MR) is a method that aims to strengthen causal inference using genetic variants as proxies or instrumental variables (IVs) for exposures, to overcome the above-mentioned biases. Since allele segregation occurs at random from parents to offspring, and alleles for a trait assort independently from those for other traits, MR studies have frequently been compared to "natural" RCTs. In biological anthropology (BA) relationships between variables of interest are usually evaluated using observational data, often remaining descriptive, and other approaches to causal inference have seldom been implemented. Here, we propose the use of MR to investigate cause and effect relationships in BA studies and provide examples to show how that can be done across areas of BA relevance, such as adaptation to the environment, nutrition and life history theory. While we consider MR a useful addition to the biological anthropologist's toolbox, we advocate the adoption of a wide range of methods, affected by different types of biases, in order to better answer the important causal questions for the discipline.
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Análise da Randomização Mendeliana , Análise da Randomização Mendeliana/métodos , Causalidade , Viés , Fenótipo , AlelosRESUMO
COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1ßrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.
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COVID-19 , Inflamassomos , Humanos , Brasil/epidemiologia , Proteínas Adaptadoras de Sinalização CARD/genética , COVID-19/genética , Predisposição Genética para Doença , Genótipo , Inflamassomos/genética , Proteínas de Neoplasias/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polimorfismo de Nucleotídeo Único , Respiração ArtificialRESUMO
Chikungunya virus (CHIKV) is transmitted by the bite of infected mosquitoes and can cause significant pathogenicity in humans. Moreover, its importance has increased in the Americas since 2013. The primary vectors for viral delivery are the mosquito species Aedes aegypti and Aedes albopictus. Several factors, including host genetic variations and immune response against CHIKV, influence the outcomes of Chikungunya disease. This work aimed to gather information about different single nucleotide polymorphisms (SNPs) in genes that influence the host immune response during an infection by CHIKV. The viral characteristics, disease epidemiology, clinical manifestations, and immune response against CHIKV are also addressed. The main immune molecules related to this arboviral disease elucidated in this review are TLR3/7/8, DC-SIGN, HLA-DRB1/HLA-DQB1, TNF, IL1RN, OAS2/3, and CRP. Advances in knowledge about the genetic basis of the immune response during CHIKV infection are essential for expanding the understanding of disease pathophysiology, providing new genetic markers for prognosis, and identifying molecular targets for the development of new drug treatments.
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Background: Genetic diversity is fundamental for the survival of species. In particular, in a climate change scenario, it is crucial that populations maintain genetic diversity so they can adapt to novel environmental conditions. Genetic diversity in wild agaves is usually high, with low genetic differentiation among populations, in part maintained by the agave pollinators such as the nectarivorous bats. In cultivated agaves, patterns of genetic diversity vary according to the intensity of use, management, and domestication stage. In Agave tequilana Weber var. azul (A. tequilana thereafter), the plant used for tequila production, clonal propagation has been strongly encouraged. These practices may lead to a reduction in genetic diversity. Methods: We studied the diversity patterns with genome-wide SNPs, using restriction site associated DNA sequencing in cultivated samples of A. tequilana from three sites of Jalisco, Mexico. For one locality, seeds were collected and germinated in a greenhouse. We compared the genomic diversity, levels of inbreeding, genetic differentiation, and connectivity among studied sites and between adults and juvenile plants. Results: Agave tequilana presented a genomic diversity of HT = 0.12. The observed heterozygosity was higher than the expected heterozygosity. Adults were more heterozygous than juveniles. This could be a consequence of heterosis or hybrid vigor. We found a shallow genetic structure (average paired FST = 0.0044). In the analysis of recent gene flow, we estimated an average migration rate among the different populations of m = 0.25. In particular, we found a population that was the primary source of gene flow and had greater genomic diversity (HE and HO ), so we propose that this population should continue to be monitored as a potential genetic reservoir. Discussion: Our results may be the consequence of more traditional management in the studied specific region of Jalisco. Also, the exchange of seeds or propagules by producers and the existence of gene flow due to occasional sexual reproduction may play an important role in maintaining diversity in A. tequilana. For populations to resist pests, to continue evolving and reduce their risk of extinction under a climate change scenario, it is necessary to maintain genetic diversity. Under this premise we encourage to continue acting in conservation programs for this species and its pollinators.
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Agave , Agave/genética , México , Heterozigoto , Bebidas Alcoólicas , GenômicaRESUMO
The coastal waters of Cuba are home to a small, endangered population of West Indian manatee, which would benefit from a comprehensive characterization of the population's genetic variation. We conducted the first genetic assessment of Cuban manatees to determine the extent of the population's genetic structure and characterize the neutral genetic diversity among regions within the archipelago. We genotyped 49 manatees at 18 microsatellite loci, a subset of 27 samples on 1703 single nucleotide polymorphisms (SNPs), and sequenced 59 manatees at the mitochondrial control region. The Cuba manatee population had low nuclear (microsatellites HE = 0.44, and SNP HE = 0.29) and mitochondrial genetic diversity (h = 0.068 and π = 0.00025), and displayed moderate departures from random mating (microsatellite FIS = 0.12, SNP FIS = 0.10). Our results suggest that the western portion of the archipelago undergoes periodic exchange of alleles based on the evidence of shared ancestry and low but significant differentiation. The southeast Guantanamo Bay region and the western portion of the archipelago were more differentiated than southwest and northwest manatees. The genetic distinctiveness observed in the southeast supports its recognition as a demographically independent unit for natural resource management regardless of whether it is due to historical isolation or isolation by distance. Estimates of the regional effective population sizes, with the microsatellite and SNP datasets, were small (all Ne < 60). Subsequent analyses using additional samples could better examine how the observed structure is masking simple isolation by distance patterns or whether ecological or biogeographic forces shape genetic patterns.
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Trichechus manatus , Animais , Trichechus manatus/genética , Cuba , Repetições de Microssatélites , Trichechus/genética , Variação Genética , Genética PopulacionalRESUMO
BACKGROUND: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. OBJECTIVE: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. METHODS: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. RESULTS: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24â6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21â4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86â7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08â63.59, p = 0.005) and a 15.69-fold (95% CI 2.46â99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59â45.54, p = 0.012) and an 8.40 fold (95% CI 1.51â46.91, p = 0.015) increased risk of steatosis, respectively, was observed. CONCLUSION: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.
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Proteínas de Transporte , Fígado Gorduroso , Hepatite C Crônica , Proteínas de Transporte/genética , Fígado Gorduroso/genética , Feminino , Genótipo , Hepacivirus , Hepatite C Crônica/genética , Humanos , Polimorfismo de Nucleotídeo Único , TriglicerídeosRESUMO
BACKGROUND: In 2013, the group of Cicero Coimbra, Brazil, reported the clinical efficacy of high doses of vitamin D3 in patients suffering from autoimmune skin disorders ("Coimbra protocol", CP). However, hypercalcemia and the subsequent impaired renal function may be major concerns raised against this protocol. METHODS: We report for the first time for a broad spectrum of autoimmune diseases in 319 patients (mean age (±SD) 43.3 ± 14.6 years, 65.5% female, 34.5% male) safety data for high doses of orally applied vitamin D3 (treatment period: up to 3.5 years) accompanied by a strict low-calcium diet and regular daily fluid intake of at least 2.5 L. RESULTS: Mean vitamin D3 dose was 35,291 ± 21,791 IU per day. The measurement of more than 6100 single relevant laboratory parameters showed all mean values (±SD) within the normal range for total serum calcium (2.4 ± 0.1 mmol/L), serum creatinine (0.8 ± 0.2 mg/dL), serum creatinine associated estimated GFR (92.5 ± 17.3 mL/min), serum cystatin C (0.88 ± 0.19 mg/L), serum TSH (1.8 ± 1 mIU/L), and for 24 h urinary calcium secretion (6.9 ± 3.3 mmol/24 h). We found a very weak relationship between the dosage of oral vitamin D3 and the subsequent calcium levels, both in serum and in urinary excretion over 24 h, respectively. CONCLUSIONS: Our data show the reliable safety of the CP in autoimmune patients under appropriate supervision by experienced physicians.
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Doenças Autoimunes , Colecalciferol , Vitamina D , Adulto , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Brasil , Cálcio/metabolismo , Colecalciferol/efeitos adversos , Colecalciferol/uso terapêutico , Creatinina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo , Vitamina D/uso terapêuticoRESUMO
Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.
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BACKGROUND A previous genome-wide association study (GWAS) identified the kinesin family member 16B (KIF16B) as a candidate gene related to sheep wool production. In this work, DNA pool sequencing and SNPscanTM high-throughput genotyping methods were used to detect single-nucleotide polymor phisms (SNPs) in the sheep KIF16B gene. The correlations between the SNPs and wool length and greasy wool yield were systematically assessed. RESULTS Forty-five SNPs were identified and 37 of them were genotyped, including 10 exon mutations, 26 intron mutations, and 1 promoter region mutation. Most of the SNPs were of medium genetic diversity and at Hardy-Weinberg equilibrium (HWE). Among them, 10 SNPs were associated with greasy wool yield and 28 SNPs impact the wool length. Five specific SNPs were found to exert significant effects on the wool length in all body parts analyzed in this study. Furthermore, linkage disequilibrium (LD) analysis was conducted among SNP loci and they were found to be significantly associated with economically important traits. Two strongly linked SNP blocks were identified within these SNPs and they might exert significant impacts on the greasy wool yield and wool length. CONCLUSIONS The identified SNPs exert significant effects on wool production and could be considered as potential DNA markers for selecting the individuals with superior phenotypes
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Animais , Lã/crescimento & desenvolvimento , Ovinos/genética , Ovinos/crescimento & desenvolvimento , Estudo de Associação Genômica Ampla/métodosRESUMO
Speciation proceeds through mechanisms that promote reproductive isolation and shape the extent of genetic variation in natural populations, and thus its study is essential to understand the evolutionary processes leading to increased biodiversity. Chromosomal rearrangements are known to facilitate reproductive isolation by hybrid sterility and favour speciation events. The genus Ipheion (Amaryllidaceae, Allioideae) is unique as its species exhibit a remarkable karyological variability but lack population-level genetic data. To unveil the diversification processes acting upon the formation of new lineages within Ipheion in the Pampas of South America, we combined morphology and karyology approaches with genotyping-by-sequencing. Our phylogenomic and population genomics results supported the taxonomic division of Ipheion into three morphological and genetically well-differentiated groups. The origin of Ipheion uniflorum was traced back to its current southern distribution area in the southern Pampean region (in Argentina), from where it had expanded to the north reaching Uruguay. Our results further suggested that chromosome rearrangements and ploidy shifts had triggered speciation events, first during the origin of I. uniflorum and later during its subsequent diversification into I. recurvifolium and I. tweedieanum, in both cases reinforced by extrinsic factors and biogeographical settings. The current study illustrates the analytical power of multidisciplinary approaches integrating phylo- and population genomics with classic analyses to reveal evolutionary processes in plants.
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Alho , Evolução Biológica , Especiação Genética , Genômica , Filogenia , Isolamento ReprodutivoRESUMO
Seed dispersal is crucial to gene flow among plant populations. Although the effects of geographic distance and barriers to gene flow are well studied in many systems, it is unclear how seed dispersal mediates gene flow in conjunction with interacting effects of geographic distance and barriers. To test whether distinct seed dispersal modes (i.e., hydrochory, anemochory, and zoochory) have a consistent effect on the level of genetic connectivity (i.e., gene flow) among populations of riverine plant species, we used unlinked single-nucleotide polymorphisms (SNPs) for eight co-distributed plant species sampled across the Rio Branco, a putative biogeographic barrier in the Amazon basin. We found that animal-dispersed plant species exhibited higher levels of genetic diversity and lack of inbreeding as a result of the stronger genetic connectivity than plant species whose seeds are dispersed by water or wind. Interestingly, our results also indicated that the Rio Branco facilitates gene dispersal for all plant species analyzed, irrespective of their mode of dispersal. Even at a small spatial scale, our findings suggest that ecology rather than geography play a key role in shaping the evolutionary history of plants in the Amazon basin. These results may help improve conservation and management policies in Amazonian riparian forests, where degradation and deforestation rates are high.
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Small farm producers' sustenance depends on their alpaca herds and the production of fiber. Genetic improvement of fiber characteristics would increase their economic benefits and quality of life. The incorporation of molecular marker technology could overcome current limitations for the implementation of genetic improvement programs. Hence, the aim of this project was the generation of an alpaca single nucleotide polymorphism (SNP) microarray. A sample of 150 Huacaya alpacas from four farms, two each in Puno and Cerro de Pasco were used for SNP discovery by genotyping by sequencing (GBS). Reduced representation libraries, two per animal, were produced after DNA digestion with ApeK1 and double digestion with Pst1-Msp1. Ten alpaca genomes, sequenced at depths between 12× to 30×, and the VicPac3.1 reference genome were used for read alignments. Bioinformatics analysis discovered 76,508 SNPs included in the microarray. Candidate genes SNPs (302) for fiber quality and color are also included. The microarray SNPs cover 90.5% of the genome length with a density of about 39 ± 2.51 SNPs/Mb of DNA at an average interval of 26.45 ± 18.57 kbp. The performance was evaluated by genotyping 30 family trios and comparing them to their pedigrees, as well as comparing microarray to GBS genotypes. Concordance values of 0.93 and 0.94 for ApeK1 and Pst1-Msp1 generated SNPs were observed. Similarly, 290 fiber quality and color candidate gene SNPs were validated. Availability of this microarray will facilitate genome-wide association studies, marker-assisted selection and, in time, genomic selection.
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Camelídeos Americanos/genética , Marcadores Genéticos/genética , Análise em Microsséries , Polimorfismo de Nucleotídeo Único/genética , Animais , Genótipo , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Fetal hemoglobin (HbF) ameliorates clinical severity of sickle cell anemia (SCA). The major loci regulating HbF levels are HBB cluster, BCL11A, and HMIP-2 (HBS1L-MYB). However, the impact of noncoding single-nucleotide polymorphisms (SNPs) in these loci on clinical outcomes and their functional role on regulating HbF levels should be better elucidated. Therefore, we performed comprehensive association analyses of 14 noncoding SNPs in five loci with HbF levels and with clinical outcomes in a cohort of 250 children with SCA from Southeastern Brazil, and further performed functional annotation of these SNPs. We found SNPs independently associated with HbF levels: rs4671393 in BCL11A (ß-coefficient = 0.28), rs9399137 in HMIP-2A (ß-coefficient = 0.16), and rs4895441 in HMIP-2B (ß-coefficient = 0.15). Patients carrying minor (HbF-boosting) alleles for rs1427407, rs93979137, rs4895441, rs9402686, and rs9494145 showed reduced count of reticulocytes (p < 0.01), while those carrying the T allele of rs9494145 showed lower white blood cell count (p = 0.002). Carriers of the minor allele for rs9402686 showed higher peripheral saturation of oxygen (p = 0.002). Patients carrying minor alleles in BCL11A showed lower risk of transfusion incidence rate ratio (IRR ≥ 1.3; p < 0.0001). This effect was independent of HbF effect (p = 0.005). Carriers of minor alleles for rs9399137 and rs9402686 showed lower risk of acute chest syndrome (IRR > 1.3; p ≤ 0.01). Carriers of the reference allele for rs4671393 showed lower risk of infections (IRR = 1.16; p = 0.01). In conclusion, patients carrying HbF-boosting alleles of BCL11A and HMIP-2 were associated with milder clinical phenotypes. Higher HbF concentration may underlie this effect.
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Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Hemoglobina Fetal/metabolismo , Proteínas de Ligação ao GTP/genética , Genes myb , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hemoglobina Fetal/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
Host single nucleotide polymorphisms (SNPs) in different genes can play a role in chronic hepatitis C virus (HCV) infection and influence the presence of hepatic fibrosis and comorbidities such as hepatic steatosis. We assessed the combined effect of SNPs in the PNPLA3, MTTP, TM6SF2, and IFNL3/IFNL4 genes in 288 Brazilian patients who were chronically infected with HCV. Hepatic fibrosis was observed in 246 (85.4%) patients and hepatic steatosis in 141 (49.0%) patients. PNPLA3 rs738409 (CG/GG) (Pâ¯=â¯0.044) and TM6SF2 rs58542926 (CT) (Pâ¯=â¯0.004) were alone associated with fibrosis, and PNPLA3 rs738409 (Pâ¯<â¯0.05, in distinct genetic models) was associated with steatosis. Multiple logistic regression of each SNP combined with HCV genotype 3 infection showed that MTTP rs1800591 (GT/TT) combined with HCV genotype 3 was associated with a 6.72-fold increased chance of hepatic steatosis (Pâ¯=â¯0.013). In the analysis of SNPs combined 2 by 2, no influence on hepatic fibrosis or steatosis was observed.
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Fígado Gorduroso/genética , Hepatite C Crônica/genética , Cirrose Hepática/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Brasil , Proteínas de Transporte/genética , Fígado Gorduroso/virologia , Feminino , Estudos de Associação Genética , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C Crônica/virologia , Humanos , Interferons/genética , Lipase/genética , Cirrose Hepática/virologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Nyssorhynchus darlingi (also known as Anopheles darlingi) is the primary malaria vector in the Amazon River Basin. In Brazil, analysis of single nucleotide polymorphisms (SNPs) previously detected three major population clusters, and a common garden experiment in a laboratory setting revealed significant population variation in life history traits. Increasing temperatures and local level variation can affect life history traits, i.e. adult longevity, that alter vectorial capacity with implications for malaria transmission in Ny. darlingi. METHODS: We investigated the population structure of Ny. darlingi from 7 localities across Brazil utilizing SNPs and compared them to a comprehensive Ny. darlingi catalog. To test the effects of local level variation on life history traits, we reared F1 progeny from the 7 localities at three constant temperatures (20, 24 and 28 °C), measuring key life history traits (larval development, food-starved adult lifespan, adult size and daily survival). RESULTS: Using nextRAD genotyping-by-sequencing, 93 of the field-collected Ny. darlingi were genotyped at 33,759 loci. Results revealed three populations (K = 3), congruent with major biomes (Amazonia, Cerrado and Mata Atlântica), with greater FST values between biomes than within. In the life history experiments, increasing temperature reduced larval development time, adult lifespan, and wing length in all localities. The variation of family responses for all traits within four localities of the Amazonia biome was significant (ANOVA, P < 0.05). Individual families within localities revealed a range of responses as temperature increased, for larval development, adult lifespan, wing length and survival time. CONCLUSIONS: SNP analysis of several Brazilian localities provided results in support of a previous study wherein populations of Ny. darlingi were clustered by three major Brazilian biomes. Our laboratory results of temperature effects demonstrated that population variation in life history traits of Ny. darlingi exists at the local level, supporting previous research demonstrating the high plasticity of this species. Understanding this plasticity and inherent variation between families of Ny. darlingi at the local level should be considered when deploying intervention strategies and may improve the likelihood of successful malaria elimination in South America.
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Anopheles/fisiologia , Características de História de Vida , Fenótipo , Temperatura , Adaptação Fisiológica/fisiologia , Animais , Brasil , Ecossistema , Malária/transmissão , Mosquitos Vetores/fisiologia , Dinâmica PopulacionalRESUMO
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), although discovered more than a century ago, is still a not very well-elucidated aspect. Individuals in the chronic phase of the disease may present asymptomatic clinical form or symptomatologies related to the cardiac, digestive systems, or both (mixed clinical form). SNPs (single nucleotide polymorphisms) have been identified as important markers because they constitute about 90% of the variation in the human genome. One of them is localized to the ACAT-1 gene (cholesterol acyltransferase 1) (rs1044925) and has been linked to lipid disorders. Some studies have suggested the interaction between T. cruzi and the lipid metabolism of the host. Therefore, the objective of the present study was to evaluate the association between the ACAT-1 gene rs1044925 SNP in relation to clinical manifestations in patients with chronic Chagas disease. A total of 135 individuals with chronic Chagas disease, 86 (63.7%) asymptomatic individuals and 49 (36.3%) symptomatic patients (22 with cardiac clinical form, 18 with digestive form and 9 with mixed form) participated in the study. To evaluate the polymorphism, the PCR-RFLP technique were used. There was a significant difference and a higher frequency of AA and AC genotypes (p = 0.047 and p = 0.016, respectively) of the ACAT-1 gene in asymptomatic chagasic individuals. The result suggests a protective character of the AA and AC genotypes of the rs1044925 SNP in relation to the presence of symptomatic clinical manifestations of the disease in chronic chagasic individuals.
Assuntos
Doença de Chagas/genética , Polimorfismo de Nucleotídeo Único , Esterol O-Aciltransferase/genética , Idoso , Doenças Assintomáticas , Doença de Chagas/parasitologia , Doença Crônica , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Trypanosoma cruzi/fisiologiaRESUMO
Phylogenetic relationships amongst the robust capuchin monkeys (genus Sapajus) are poorly understood. Morphology-based taxonomies have recognized anywhere from one to twelve different species. The current IUCN (2017) classification lists eight robust capuchins: S. xanthosternos, S. nigritus, S. robustus, S. flavius, S. libidinosus, S. cay, S. apella and S. macrocephalus. Here, we assembled the first phylogenomic data set for Sapajus using ultra-conserved elements (UCEs) to reconstruct a capuchin phylogeny. All phylogenomic analyses strongly supported a deep divergence of Sapajus and Cebus clades within the capuchin monkeys, and provided support for Sapajus nigritus, S. robustus and S. xanthosternos as distinct species. However, the UCE phylogeny lumped the putative species S. cay, S. libidinosus, S. apella, S. macrocephalus, and S. flavius together as a single widespread lineage. A SNP phylogeny constructed from the UCE data was better resolved and recovered S. flavius and S. libidinosus as sister species; however, S. apella, S. macrocephalus, and S. cay individuals were recovered in two geographic clades, from northeastern and southwestern Amazon, rather than clustering by currently defined morphospecies. STRUCTURE analysis of population clustering revealed widespread admixture among Sapajus populations within the Amazon and even into the Cerrado and Atlantic Forest. Difficulty in assigning species by morphology may be a result of widespread population admixture facilitated through frequent movement across major rivers and even ecosystems by robust capuchin monkeys.
Assuntos
Cebus/classificação , Cebus/genética , Pool Gênico , Genômica , Filogenia , Animais , Calibragem , Cebinae , Ecossistema , Genética Populacional , Geografia , Funções Verossimilhança , Polimorfismo de Nucleotídeo Único/genética , América do SulRESUMO
INTRODUCTION AND AIM: Hepatitis B virus (HBV) infection remains a public health problem worldwide. In addition, HBV infection results are influenced by various virological, immunological, and genetic factors. Inducible T-cell costimulator (ICOS) polymorphisms involving chronic HBV infection have been confirmed in previous studies. This study was to explore the effects of ICOS single nucleotide polymorphisms in HBV subtypes and their interactions with viral mutations on HBV infection outcomes. MATERIAL AND METHODS: A total of 1,636 Han Chinese individuals were recruited, including 47 asymptomatic HBV carriers (ASC), 353 chronic hepatitis B (CHB) patients, 327 HBV-related liver cirrhosis (LC) patients, 193 HBV-related hepatocellular carcinoma (HCC) patients, 464 patients with spontaneous recovery from HBV infection (SR), and 252 healthy controls (HC). DNA samples from these subjects were genotyped for four ICOS SNPs (rs11883722, rs10932029, rs1559931, and rs4675379). Direct sequencing was used to determine the HBV mutations in the enhancer II, basal core promoter, and pre-core regions. RESULTS: We found that the genotype "TC" of ICOS rs10932029 SNP was associated with decreased HBV-related LC risk in the genotype C group. Additionally, the A1762T, G1764A and A1762T/G1764A mutations were associated with an increased risk of LC in the genotype C group. Further study indicated that interactions between ICOS rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations significantly decreased the LC risk in the genotype C group. CONCLUSION: The rs10932029 genotype "TC" might be an LC-protective factor for HBV genotype C infection. The interactions between the rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations could decrease the risk of LC.