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Introduction: Chronic obstructive pulmonary disease (COPD) is associated with tobacco smoking and biomass-burning smoke exposure. Toll-like receptor 4 (TLR4) single-nucleotide polymorphisms (SNPs) may contribute to its pathogenesis. The study aimed to assess the association of rs4986790 and rs4986791 in the TLR4 gene in a Mexican mestizo population with COPD secondary to tobacco smoking (COPD-TS) and biomass-burning smoke (COPD-BBS) and to evaluate whether the genotypes of risk affect cytokine serum levels. Materials and methods: We enrolled 2,092 participants and divided them into two comparisons according to their environmental exposure. SNPs were genotyped using TaqMan probes. Serum cytokine levels (IL-4, IL-5, IL-6, IL-10, and INF-γ) were quantified by ELISA. Results: The rs4986790 AA genotype in COPD-TS was associated with a higher COPD risk (OR = 3.53). Haplotype analysis confirmed this association, identifying a block containing the rs4986790 allele (A-C, OR = 3.11). COPD-TS exhibited elevated IL-6, IL-4, and IL-5 levels compared with smokers without COPD (SWOC), whereas COPD-BBS displayed higher IFN-γ, IL-6, and IL-10 levels. The AA carriers in the COPD-TS group had elevated IL-4, IL-5, and IFN-γ compared with carriers of AG or GG. Conclusion: The rs4986790 common allele and the A-C haplotype (rs4986790-rs4986791) were associated with a higher COPD risk in smokers; COPD patients carrying the AA genotype showed increased pro-inflammatory cytokines.
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Genótipo , Interferon gama , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica , Receptor 4 Toll-Like , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/etiologia , Masculino , Feminino , Receptor 4 Toll-Like/genética , Pessoa de Meia-Idade , Interferon gama/genética , Interferon gama/sangue , Idoso , Interleucina-4/genética , Interleucina-4/sangue , Biomassa , Predisposição Genética para Doença , Interleucina-5/genética , Interleucina-5/sangue , Fumaça/efeitos adversos , México , Adulto , Fumantes , Fumar/efeitos adversosRESUMO
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
Genetic variability within the same fish species could confer soybean meal (SBM) tolerance in some individuals, thus favoring growth. This study investigates the single-nucleotide polymorphisms (SNPs) in differentially expressed genes (DEGs) favoring SBM tolerance in higher-growth zebrafish (Danio rerio). In a previous work, nineteen families of zebrafish were fed a fish meal diet (100FM control diet) or SBM-based diets supplemented with saponin (50SBM + 2SPN-experimental diet), from juvenile to adult stages. Individuals were selected from families with a genotype-by-environment interaction higher (170 ± 18 mg) or lower (76 ± 10 mg) weight gain on 50SBM + 2SPN in relation to 100FM. Intestinal transcriptomic analysis using RNA-seq revealed six hundred and sixty-five differentially expressed genes in higher-growth fish fed 50SBM + 2SPN diet. In this work, using these results, 47 SNPs in DEGs were selected. These SNPs were genotyped by Sequenom in 340 zebrafish that were fed with a 50SBM + 2SPN diet or with 100FM diet. Marker-trait analysis revealed 4 SNPs associated with growth in 3 immunity-related genes (aif1l, arid3c, and cst14b.2) in response to the 50SBM + 2SPN diet (p-value < 0.05). Two SNPs belonging to aif1l y arid3c produce a positive (+19 mg) and negative (-26 mg) effect on fish growth, respectively. These SNPs can be used as markers to improve the early selection of tolerant fish to SBM diet or other plant-based diets. These genes can be used as biomarkers to identify SNPs in commercial fish, thus contributing to the aquaculture sustainability.
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Ração Animal , Glycine max , Polimorfismo de Nucleotídeo Único , Peixe-Zebra , Animais , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Glycine max/genética , Dieta/veterinária , Genótipo , Perfilação da Expressão Gênica , TranscriptomaRESUMO
Introduction: The coconut tree crop (Cocos nucifera L.) provides vital resources for millions of people worldwide. Coconut germplasm is largely classified into 'Tall' (Typica) and 'Dwarf' (Nana) types. While Tall coconuts are outcrossing, stress tolerant, and late flowering, Dwarf coconuts are inbred and flower early with a high rate of bunch emission. Precocity determines the earlier production of a plantation and facilitates management and harvest. Methods: A unique outbred F2 population was used, generated by intercrossing F1 hybrids between Brazilian Green Dwarf from Jiqui (BGDJ) and West African Tall (WAT) cultivars. Single-nucleotide polymorphism (SNP) markers fixed for alternative alleles in the two varieties, segregating in an F2 configuration, were used to build a high-density linkage map with ~3,000 SNPs, anchored to the existing chromosome-level genome assemblies, and a quantitative trait locus (QTL) mapping analysis was carried out. Results: The linkage map established the chromosome numbering correspondence between the two reference genome versions and the relationship between recombination rate, physical distance, and gene density in the coconut genomes. Leveraging the strong segregation for precocity inherited from the Dwarf cultivar in the F2, a major effect QTL with incomplete dominance was mapped for flowering time. FLOWERING LOCUS T (FT) gene homologs of coconut previously described as putatively involved in flowering time by alternative splice variant analysis were colocalized within a ~200-kb window of the major effect QTL [logarithm of the odds (LOD) = 11.86]. Discussion: Our work provides strong phenotype-based evidence for the role of the FT locus as the putative underlying functional variant for the flowering time difference between Dwarf and Tall coconuts. Major effect QTLs were also detected for developmental traits of the palm, plausibly suggesting pleiotropism of the FT locus for other precocity traits. Haplotypes of the two SNPs flanking the flowering time QTL inherited from the Dwarf parent BGDJ caused a reduction in the time to flower of approximately 400 days. These SNPs could be used for high-throughput marker-assisted selection of early-flowering and higher-productivity recombinant lines, providing innovative genetic material to the coconut industry.
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The conservation of animal genetic resources refers to measures taken to prevent the loss of genetic diversity in livestock populations, including the protection of breeds from extinction. Creole cattle populations have suffered a drastic reduction in recent decades owing to absorbent crosses or replacement with commercial breeds of European or Indian origin. Genetic characterization can serve as a source of information for conservation strategies to maintain genetic variation. The objective of this work was to evaluate the levels of inbreeding and kinship through the use of genomic information. A total of 903 DNAs from 13 cattle populations from Argentina, Bolivia and Uruguay were genotyped using an SNP panel of 48 K. Also, a dataset of 76 K SNPs from Peruvian Creole was included. Two inbreeding indices (FROH and Fhat2) and kinship relationships were calculated. In addition, effective population size (Ne), linkage disequilibrium, population composition and phylogenetic relationships were estimated. In Creole cattle, FROH ranged from 0.14 to 0.03, and Fhat2 was close to zero. The inferred Ne trends exhibited a decline toward the present for all populations, whereas Creole cattle presented a lower magnitude of Ne than foreign breeds. Cluster analysis clearly differentiated the taurine and Zebu components (K2) and showed that Bolivian Creole cattle presented Zebu gene introgression. Despite the population reduction, Creole populations did not present extreme values of consanguinity and kinship and maintain high levels of genetic diversity. The information obtained in this work may be useful for planning conservation programmes for these valuable local animal genetic resources.
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Endogamia , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Uruguai , Bolívia , Cruzamento , Desequilíbrio de Ligação , Filogenia , Genótipo , Argentina , Linhagem , Variação Genética , Genética Populacional , Densidade DemográficaRESUMO
The genetic contributions of Neanderthals to the modern human genome have been evidenced by the comparison of present-day human genomes with paleogenomes. Neanderthal signatures in extant human genomes are attributed to intercrosses between Neanderthals and archaic anatomically modern humans (AMHs). Although Neanderthal signatures are well documented in the nuclear genome, it has been proposed that there is no contribution of Neanderthal mitochondrial DNA to contemporary human genomes. Here we show that modern human mitochondrial genomes contain 66 potential Neanderthal signatures, or Neanderthal single nucleotide variants (N-SNVs), of which 36 lie in coding regions and 7 result in nonsynonymous changes. Seven N-SNVs are associated with traits such as cycling vomiting syndrome, Alzheimer's disease and Parkinson's disease, and two N-SNVs are associated with intelligence quotient. Based on recombination tests, principal component analysis (PCA) and the complete absence of these N-SNVs in 41 archaic AMH mitogenomes, we conclude that convergent evolution, and not recombination, explains the presence of N-SNVs in present-day human mitogenomes.
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Doença de Alzheimer , Genoma Mitocondrial , Homem de Neandertal , Humanos , Animais , Homem de Neandertal/genética , Mutação , NucleotídeosRESUMO
DNAM-1 (CD226) is an activating receptor expressed in CD8+ T cells, NK cells, and monocytes. It has been reported that two SNPs in the DNAM-1 gene, rs763361 C>T and rs727088 G>A, have been associated with different autoimmune diseases; however, the role of DNAM-1 in ankylosing spondylitis has been less studied. For this reason, we focused on the study of these two SNPs in association with ankylosing spondylitis. For this, 34 patients and 70 controls were analyzed using endpoint PCR with allele-specific primers. Our results suggest that rs763361 C>T is involved as a possible protective factor under the CT co-dominant model (OR = 0.34, 95% CI = 0.13-0.88, p = 0.022) and the CT + TT dominant model (OR = 0.39, 95% CI = 0.17-0.90, p = 0.025), while rs727088 G>A did not show an association with the disease in any of the inheritance models. When analyzing the relationships of the haplotypes, we found that the T + A haplotype (OR = 0.31, 95% CI = 0.13-0.73, p = 0.0083) is a protective factor for developing the disease. In conclusion, the CT and CT + TT variants of rs763361 C>T and the T + A haplotype were considered as protective factors for developing ankylosing spondylitis.
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Since the first introduction from North America more than a century ago, rainbow trout (Oncorhynchus mykiss) have rapidly established self-sustaining populations in major river basins of Patagonia. Many generations later, only the freshwater resident life history is expressed in the Chubut and Negro rivers of northern Argentinian Patagonia, whereas both the resident and anadromous life histories are found in the Santa Cruz River of southern Argentina. Despite previous studies that have tried to identify the sources of these introduced populations, uncertainty still exists. Here we combined data from many single-nucleotide polymorphisms and microsatellite loci in O. mykiss populations from Argentina and North America to evaluate putative source populations, gene flow between Argentinian river basins, and genetic diversity differences between Argentinian and North American populations. We found that populations from northern and southern Patagonia are highly differentiated and have limited gene flow between them. Phylogeographic analysis also confirmed that they have separate origins, with the northern populations most closely related to the domesticated rainbow trout strains that are raised worldwide and the Santa Cruz River populations most closely related to North American populations from California and Oregon that have an anadromous component. In addition, fish with different life histories in the Santa Cruz River were found to constitute a single interbreeding population. No evidence was found of reduced genetic variation in introduced rainbow trout, suggesting multiple contributing sources. In spite of these advances in understanding, significant questions remain regarding the origins and evolution of the introduced O. mykiss in Patagonia.
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Fluxo Gênico , Variação Genética , Repetições de Microssatélites , Oncorhynchus mykiss , Polimorfismo de Nucleotídeo Único , Animais , Oncorhynchus mykiss/genética , Argentina , Rios , Filogeografia , Genética PopulacionalRESUMO
Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.
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Subfamília B de Transportador de Cassetes de Ligação de ATP , Citocromo P-450 CYP3A , Imunossupressores , Transplante de Rim , Polimorfismo de Nucleotídeo Único , Tacrolimo , Humanos , Citocromo P-450 CYP3A/genética , Transplante de Rim/efeitos adversos , Tacrolimo/sangue , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Feminino , Masculino , Polimorfismo de Nucleotídeo Único/genética , Adulto , México , Imunossupressores/farmacocinética , Imunossupressores/sangue , Imunossupressores/administração & dosagem , Pessoa de Meia-Idade , Genótipo , Rejeição de Enxerto/genéticaRESUMO
Platonia insignis is a fruit tree native to Brazil of increasing economic importance, with its pulp trading among the highest market values. This study aimed to evaluate the structure and genomic diversity of P. insignis (bacurizeiro) accessions from six locations in the Brazilian States of Roraima, Amazonas, Pará (Amazon biome), and Maranhão (Cerrado biome). A total of 2031 SNP markers were obtained using genotyping-by-sequencing (GBS), from which 625 outlier SNPs were identified. High genetic structure was observed, with most of the genetic variability (59%) concentrated among locations, mainly between biomes (Amazon and Cerrado). A positive and significant correlation (r = 0.85; p < 0.005) was detected between genetic and geographic distances, indicating isolation by distance. The highest genetic diversity was observed for the location in the Cerrado biome (HE = 0.1746; HO = 0.2078). The locations in the Amazon biome showed low genetic diversity indexes with significant levels of inbreeding. The advance of urban areas, events of burning, and expansion of agricultural activities are most probably the main factors for the genetic diversity reduction of P. insignis. Approaches to functional analysis showed that most of the outlier loci found may be related to genes involved in cellular and metabolic processes.