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ObjectiveTo establish a rapid method for evaluating the heterozygosity of Murraya paniculata germplasm materials and provide as a foundation for developing germplasm breeding and innovation measures for M. paniculata. MethodSingle nucleotide polymorphisms （SNPs） were screened from the genome resequencing data of 65 plants of M. paniculata. A self-written script was used to transform 20 SNPs into restriction fragment length polymorphism （RFLP） markers. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was employed to detect the 20 RFLP markers in 12 M. paniculata germplasm accessions， and the heterozygosity of M. paniculata germplasm accessions was calculated based on the number of enzyme-cutting bands at the 20 RFLP marker sites. Plink was used to calculate the whole genome heterozygosity of 12 M. paniculata germplasm accessions， and the results obtained with different methods were compared. ResultThere was no significant difference in the heterozygosity calculated by the PCR-RFLP method and the genome resequencing method. The PCR-RFLP and genome resequencing methods identified 8 and 9 germplasm accessions， respectively， with a heterozygosity level less than 30%. Seven germplasm accessions with heterozygosity less than 30.00% were calculated by both methods. ConclusionThe PCR-RFLP method established in this study for evaluating the heterozygosity of M. paniculata germplasm demonstrates the precision of 87.5% and the accuracy of 77.8%. This method serves as a reference for developing heterozygosity evaluation methods in other medicinal plant germplasm resources.
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Objective@#Recent GWAS largely conducted in European populations have successfully identified multiple genetic risk variants associated with Type 2 Diabetes Mellitus (T2DM). However, the effects conferred by these variants in the Pakistani population have not yet been fully elucidated. The objective of this study was to examine European GWAS- identified T2DM risk variants in the Pakistani Pashtun population to better understand the shared genetic basis of T2DM in the European and Pakistani cohorts.@*Methodology@#A total of 100 T2DM patients and 100 healthy volunteers of Pashtun ethnicity were enrolled in this study. Both groups were genotyped for 8 selected single nucleotide polymorphisms (SNPs) using the Sequenom MassARRAY® platform. The association between selected SNPs and T2DM was determined by using appropriate statistical tests.@*Results@#Of the 8 studied SNPs, 5 SNPs, SLC30A8/ rs13266634 (p=0.031, OR=2.13), IGF2BP2/ rs4402960 (p=0.001, OR=3.01), KCNJ11/ rs5219 (p=0.042, OR=1.78), PPARG/ rs1801282 (p=0.042, OR=2.81) and TCF7L2/ rs7903146 (p=0.00006, 3.41) had a significant association with T2DM. SNP GLIS3/ rs7041847 (p=0.051, OR=2.01) showed no sufficient evidence of association. SNPs KCNQ1/ rs2237892 (p=0.140, OR=1.61) and HHEX/IDE/ s1111875 (p=0.112, OR=1.31) showed opposite allelic effects and were not validated for T2DM risk in the study population. Among the studied SNPs, TCF7L2/ rs7903146 showed the most significant association.@*Conclusion@#Our study finding indicates that selected genome-wide significant T2DM risk variants previously identified in European descent also increase the risk of developing T2DM in the Pakistani Pashtun population.
Subject(s)
Diabetes Mellitus, Type 2ABSTRACT
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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Insulin resistance (IR), secretion of insulin, and abnormalities of lipid metabolism are all markers of type 2 diabetes (T2DM), which is a progressive and complex metabolic disorder. Major risk factors for the development of T2DM were identified as genetic, environmental, and lifestyle factors. Several studies found that many genes contribute to T2DM susceptibility after glucose tolerance. Adenosine Binding Cassette Transporter Proteins 1 is a member of the ABC gene superfamily that is involved in cholesterol transport and HDL cholesterol (HDL-C) biosynthesis. Abnormal cholesterol metabolism, particularly high-density lipoprotein, has been related to genetic variations in the ABCA1 gene (HDL-C). Previous research suggested that ABCA1 gene polymorphisms may a hereditary risk factor for type 2 diabetes, along with lower HDL levels in various populations.
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ABSTRACT Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1β release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1β rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.
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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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Aims@#The cucumber mosaic virus (CMV) is categorized under the genus Cucumovirus and family Bromoviridae. This virus is known to infect over 1200 plant species from 100 families, including ornamental and horticultural plants. In this study, we pioneered a global genome comparison to decipher the unknown orchestrators behind the virulence and pathogenicity of CMV via the discovery of important single nucleotide polymorphic markers.@*Methodology and results@#As a result, the genome size was found to be a potential preliminary country-specific marker for South Korea and the GC content can be utilized to preliminarily differentiate Turkey isolates from the others. The motif analysis as well as whole genome and coat protein phylogenetic trees were unable to form country-specific clusters. However, the coat protein haplotype analysis had successfully unconcealed country-specific single nucleotide polymorphic markers for Iran, Turkey and Japan isolates. Moreover, coat protein modelling and gene ontology prediction depicted high conservation across CMV isolates from different countries.@*Conclusion, significance and impact of study@#The country-specific single nucleotide polymorphic markers unearthed in this study may provide significant data towards the profiling of varying virulence and pathogenicity of CMV across the globe in time to combat the yield loss driven by this virus thru the most efficacious biological control measures in the future.
Subject(s)
Genome, MicrobialABSTRACT
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.
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ABSTRACT Objective: The aim of this study was to evaluate the serum activity of PON1 in women according to SNPs L55M and T-107C and diet composition. Materials and methods: Blood and serum samples from 26 women were used. DNA extraction, PCR and digestion with restriction enzymes of the PCR fragment were performed for genotyping the PON1 SNPs T-107C and L55M. Serum PON1 activity was measured in a single time point. Patients completed the semi-quantitative food frequency questionnaire and diet composition was estimated. Results: Genotypic distribution for L55M SNP was 56% for the LL genotype, 32% for LM and 12% for MM; for the PON1 C(-107)T SNP it was 28% for the TT genotype, 41% for CT and 31% for CC. Individuals with C and L alleles had higher serum PON1 activity. Combining the two SNPs, we observed that individuals carrying the LL and CC genotypes had twice the activity of carriers of the TT and MM genotypes. Considering food intake, no significant difference was observed between genotypes and intake levels. Conclusion: PON1 T(-107)C and L55M SNPs exert a strong effect on serum PON1 activity in an additive manner and are more important than diet to predict serum PON1 activity.
Subject(s)
Polymorphism, Single Nucleotide , Aryldialkylphosphatase/genetics , Diet , Alleles , GenotypeABSTRACT
Trata-se de uma revisão de escopo que objetivou relatar as evidências científicas reportadas na literatura referentes a polimorfismos genéticos de nucleotídeo único (SNPs) e a sua relação com o desenvolvimento de sintomas depressivos em pessoas com câncer. A pergunta de pesquisa que norteou esta revisão foi: "Quais polimorfismos genéticos de nucleotídeo único estão relacionados ao desenvolvimento de sintomas depressivos em pacientes oncológicos?". Para a sua condução foi utilizado o referencial teórico proposto por Arksey & O'Malley (2005), acrescido de ampliações de Levac, Colquhoun & O'Brien (2010) e Colquhoun, Levac & O'Brien (2014). Realizou-se buscas sistematizadas nas seguintes bases de dados: PubMed, Embase, PsychInfo, Web of Science e Scopus. Encontrou-se 1946 referências únicas e, após rigorosa seleção, 10 artigos atenderam aos três critérios de inclusão propostos: (1) estudos clínicos conduzidos com pacientes oncológicos; (2) apresentar relação entre SNPs e o desenvolvimento de sintomas depressivos; (3) publicados em português, inglês ou espanhol. Dos 10 artigos incluídos na amostra final, 70% tratava-se de estudos longitudinais, a maioria produzidos nos Estados Unidos (40%), com publicação predominante entre os anos 2012-2014 (60%). A população predominantemente estudada foram mulheres acometidas por câncer de mama (60%) e os sintomas depressivos foram, em sua maioria, avaliados por intermédio de instrumentos validados cientificamente (80%). Os SNPs relacionados aos sintomas depressivos foram encontrados, sobretudo, em genes da via inflamatória (6/11, 54,5%), e o polimorfismo mais estudado foi o rs6265 do gene BDNF, da via de transdução de sinais (4/11, 36,3%). Os principais achados dessa revisão, demonstram que portadores do genótipo Met-BDNF tendem a apresentar maior risco de desenvolvimento e agravamento dos sintomas depressivos. Além disso, os SNPs de genes da via da inflamação, especialmente aqueles relacionados à produção de citocinas pró-inflamatórias, podem desempenhar um importante papel preditivo de sintomas depressivos, na referida população. Portanto, pode-se concluir que as evidências disponíveis na literatura apontam que o polimorfismo do gene BDNF Val66Met (rs6265) e SNPs do sistema imunológico, em especial da via inflamatória, despontam como potenciais marcadores biológicos, no contexto do desenvolvimento de sintomas depressivos em pacientes oncológicos
This is a scoping review that aimed to report the scientific evidence reported in the literature regarding single nucleotide genetic polymorphisms (SNPs) and their relation with the development of depressive symptoms in people with cancer. The research question that guided this review was: "Which single nucleotide genetic polymorphisms are related to the development of depressive symptoms in cancer patients?". The theoretical reference proposed by Arksey & O'Malley (2005) was used to conduct it, plus extensions by Levac, Colquhoun & O'Brien (2010) and Colquhoun, Levac & O'Brien (2014). Systematic searches were carried out in the following databases: PubMed, Embase, PsychInfo, Web of Science, and Scopus. 1946 unique references were found and, after rigorous selection, 10 articles met the three proposed inclusion criteria: (1) clinical studies conducted with cancer patients; (2) presenting a relation between SNPs and the development of depressive symptoms; (3) published in Portuguese, English or Spanish. Of the 10 articles included in the final sample, 70% were longitudinal studies, most of them produced in the United States (40%), with a predominant publication between the years 2012-2014 (60%). The predominantly studied population were women affected by breast cancer (60%) and the depressive symptoms were mostly evaluated using scientifically validated instruments (80%). SNPs related to depressive symptoms were found, mainly, in genes of the inflammatory pathway (6/11, 54.5%), and the most studied polymorphism was the rs6265 of the BDNF gene, of the signal transduction pathway (4/11, 36.3%). The main findings of this review demonstrate that patients with the Met-BDNF genotype tend to have a higher risk of developing and worsening depressive symptoms. In addition, the SNPs of genes in the inflammation pathway, especially those related to the production of pro-inflammatory cytokines, can play an important predictive role of depressive symptoms in this population. Therefore, it can be concluded that the evidence available in the literature indicates that the polymorphism of the BDNF gene Val66Met (rs6265) and SNPs of the immune system, especially of the inflammatory pathway, emerge as potential biological markers, in the context of the development of depressive symptoms in oncological patients
Subject(s)
Polymorphism, Genetic , Depression , Neoplasms , NucleotidesABSTRACT
Introducción: Alternaria spp y Candida spp. son hongos patógenos de ambientes interiores como la casa, la oficina, el aula, etc., causan enfermedades como asma crónica e infecciones sistémicas en individuos inmunodeprimidos a través de la secreción de diversas sustancias tóxicas. Los ambientadores a base de productos químicos disponibles comercialmente que se utilizan para controlar la carga de hongos en el ambiente interior no son beneficiosos para la salud humana. Objetivo: proporcionar una alternativa viable en forma de enfoque basado en nanopartículas para el manejo de hongos transmitidos por el aire. Metodología: aislamiento, identificación microscópica y bioquímica de hongos de interior; Síntesis de nanopartículas de azufre (SNP) mediadas por Azadirachta indica, su detección y caracterización; y evaluación in vitro de SNP contra hongos aislados presentes en el ambiente interior. Resultado: Los hongos aislados se identificaron como especies de Alternaria spp y Candida spp. Los SNP mostraron máximos de absorbancia a 291 nm. El análisis NTA mostró un tamaño medio de 188,4 nm y un potencial zeta de -4,94 mV, lo que representa una síntesis de SNP estables. El patrón XRD confirmó la naturaleza cristalina cúbica centrada en la cara de los SNP. El espectro FTIR representó la presencia de compuestos polihidroxilo, nitrilo, ceto, aromáticos y carboxílicos que estabilizaron los SNP. Los ensayos antifúngicos demostraron la actividad significativa de los SNP formulados y del ambientador infundido con aceite de eucalipto. Conclusión: Los SNP mediados por A. indica se pueden aplicar en la formulación y fabricación de un ambientador ecológico para el manejo de hongos patógenos de interior como Alternaria spp y Candida spp.
Introduction: Alternaria spp. and Candida spp. are the main fungal pathogen of indoor environment like house, office, classroom, etc. These may cause various diseases and infections like systemic infections, or chronic asthma in immunocompromised individuals through secretion of various toxic substances. Chemical-based commercially available room fresheners used to control the fungal load of indoor environment are not beneficial to human health. Objective: was to provide viable alternative in the form of nanoparticle-based approach for the management of air-borne fungi. Methodology: The present study primarily focuses on the isolation, microscopic and biochemical identification of indoor fungi; Azadirachta indica-mediated sulphur nanoparticles (SNPs) synthesis, their detection and characterization; and in vitro assessment of SNPs against isolated fungi present in indoor environment. Result: The isolated fungi were identified as Alternaria spp and Candida spp. The SNPs showed absorbance maxima at 291 nm. NTA analysis showed average size of 188.4 nm, and zeta potential of -4.94 mV which represented synthesis of stable SNPs. XRD pattern confirmed the face centered cubic, crystalline nature of SNPs. FTIR spectrum depicted the presence of polyhydroxyl, nitrile, keto, aromatic and carboxylic compounds which stabilized the SNPs. The antifungal assays demonstrated the significant activity of the formulated SNPs and eucalyptus oil infused air freshener. Conclusion: It can be concluded that A. indica-mediated SNPs can be applied in the formulation and manufacture of an ecofriendly air freshener for the management of indoor fungal pathogens like Alternaria spp. and Candida spp.
Subject(s)
Nanoparticles , Antifungal Agents , Candida , AlternariaABSTRACT
Trata-se de uma revisão de escopo que objetivou relatar as evidências científicas reportadas na literatura referentes a polimorfismos genéticos de nucleotídeo único (SNPs) e a sua relação com o desenvolvimento de sintomas depressivos em pessoas com câncer. A pergunta de pesquisa que norteou esta revisão foi: "Quais polimorfismos genéticos de nucleotídeo único estão relacionados ao desenvolvimento de sintomas depressivos em pacientes oncológicos?". Para a sua condução foi utilizado o referencial teórico proposto por Arksey & O'Malley (2005), acrescido de ampliações de Levac, Colquhoun & O'Brien (2010) e Colquhoun, Levac & O'Brien (2014). Realizou-se buscas sistematizadas nas seguintes bases de dados: PubMed, Embase, PsychInfo, Web of Science e Scopus. Encontrou-se 1946 referências únicas e, após rigorosa seleção, 10 artigos atenderam aos três critérios de inclusão propostos: (1) estudos clínicos conduzidos com pacientes oncológicos; (2) apresentar relação entre SNPs e o desenvolvimento de sintomas depressivos; (3) publicados em português, inglês ou espanhol. Dos 10 artigos incluídos na amostra final, 70% tratava-se de estudos longitudinais, a maioria produzidos nos Estados Unidos (40%), com publicação predominante entre os anos 2012-2014 (60%). A população predominantemente estudada foram mulheres acometidas por câncer de mama (60%) e os sintomas depressivos foram, em sua maioria, avaliados por intermédio de instrumentos validados cientificamente (80%). Os SNPs relacionados aos sintomas depressivos foram encontrados, sobretudo, em genes da via inflamatória (6/11, 54,5%), e o polimorfismo mais estudado foi o rs6265 do gene BDNF, da via de transdução de sinais (4/11, 36,3%). Os principais achados dessa revisão, demonstram que portadores do genótipo Met-BDNF tendem a apresentar maior risco de desenvolvimento e agravamento dos sintomas depressivos. Além disso, os SNPs de genes da via da inflamação, especialmente aqueles relacionados à produção de citocinas pró-inflamatórias, podem desempenhar um importante papel preditivo de sintomas depressivos, na referida população. Portanto, pode-se concluir que as evidências disponíveis na literatura apontam que o polimorfismo do gene BDNF Val66Met (rs6265) e SNPs do sistema imunológico, em especial da via inflamatória, despontam como potenciais marcadores biológicos, no contexto do desenvolvimento de sintomas depressivos em pacientes oncológicos
This is a scoping review that aimed to report the scientific evidence reported in the literature regarding single nucleotide genetic polymorphisms (SNPs) and their relation with the development of depressive symptoms in people with cancer. The research question that guided this review was: "Which single nucleotide genetic polymorphisms are related to the development of depressive symptoms in cancer patients?". The theoretical reference proposed by Arksey & O'Malley (2005) was used to conduct it, plus extensions by Levac, Colquhoun & O'Brien (2010) and Colquhoun, Levac & O'Brien (2014). Systematic searches were carried out in the following databases: PubMed, Embase, PsychInfo, Web of Science, and Scopus. 1946 unique references were found and, after rigorous selection, 10 articles met the three proposed inclusion criteria: (1) clinical studies conducted with cancer patients; (2) presenting a relation between SNPs and the development of depressive symptoms; (3) published in Portuguese, English or Spanish. Of the 10 articles included in the final sample, 70% were longitudinal studies, most of them produced in the United States (40%), with a predominant publication between the years 2012-2014 (60%). The predominantly studied population were women affected by breast cancer (60%) and the depressive symptoms were mostly evaluated using scientifically validated instruments (80%). SNPs related to depressive symptoms were found, mainly, in genes of the inflammatory pathway (6/11, 54.5%), and the most studied polymorphism was the rs6265 of the BDNF gene, of the signal transduction pathway (4/11, 36.3%). The main findings of this review demonstrate that patients with the Met-BDNF genotype tend to have a higher risk of developing and worsening depressive symptoms. In addition, the SNPs of genes in the inflammation pathway, especially those related to the production of pro-inflammatory cytokines, can play an important predictive role of depressive symptoms in this population. Therefore, it can be concluded that the evidence available in the literature indicates that the polymorphism of the BDNF gene Val66Met (rs6265) and SNPs of the immune system, especially of the inflammatory pathway, emerge as potential biological markers, in the context of the development of depressive symptoms in oncological patients
Subject(s)
Biomarkers , Polymorphism, Single Nucleotide/drug effects , Depression , NeoplasmsABSTRACT
Intrauterine growth restriction (IUGR) is related to a higher risk of neonatal mortality, minor cognitive deficit, metabolic syndrome, and cardiovascular disease in adulthood. In previous studies, genetic variants in the FTO (fat mass and obesity-associated) and PPARγ (peroxisome proliferator-activated receptor-gamma) genes have been associated with metabolic disease, body mass index, and obesity among other outcomes. We studied the association of selected FTO (rs1421085, rs55682395, rs17817449, rs8043757, rs9926289, and rs9939609) and PPARγ (rs10865710, rs17036263, rs35206526, rs1801282, rs28763894, rs41516544, rs62243567, rs3856806, and rs1805151) single-nucleotide polymorphisms (SNPs) with IUGR, through a case-control study in a cohort of live births that occurred from June 1978 to May 1979 in a Brazilian city. We selected 280 IUGR cases and 256 controls for analysis. Logistic regression was used to jointly analyze the SNPs as well as factors such as maternal smoking, age, and schooling. We found that the PPARγ rs41516544 increased the risk of IUGR for male offspring (OR 27.83, 95%CI 3.65-212.32) as well as for female offspring (OR=8.94, 95%CI: 1.96-40.88). The FTO rs9939609 TA genotype resulted in a reduced susceptibility to IUGR for male offspring only (OR=0.47, 95%CI: 0.26-0.86). In conclusion, we demonstrated that PPARγ SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.
Subject(s)
Humans , Male , Female , Adult , PPAR gamma/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Brazil/epidemiology , Body Mass Index , Case-Control Studies , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Fetal Growth Retardation/genetics , GenotypeABSTRACT
ABSTRACT Background: Immunological life-threatening complications frequently occur in post-hematopoietic stem cell transplantation (HSCT), despite matching recipient and donor (R/D) pairs for classical human leukocyte antigens (HLA). Studies have shown that R/D non-HLA disparities within the major histocompatibility complex (MHC) are associated with adverse effects post-HSCT. Methods: We investigated the impact of mismatches of single-nucleotide polymorphisms (SNPs) in C4A/C4B genes, for showing the highest diversity in the MHC gamma block, on 238 patients who underwent HLA 10/10 unrelated donor (URD) HSCT. The endpoints were acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD) and mortality. One hundred and twenty-nine R/D pairs had 23 C4-SNPs typed by PCR-SSP (Gamma-Type™v.1.0), and 109 R/D pairs had these 23 SNPs identified by next-generation sequencing (NGS) using the Illumina platform. Results: The percentage of patients who received HSC from HLA 10/10 donors with 1-7 mismatches was 42.9%. The R/D pairs were considered C4 mismatched when bearing at least one disparity. These mismatches were not found to be risk factors for aGVHD, cGVHD or mortality after unrelated HSCT when SNPs were analyzed together (matched or mm ≥ 1), independently or according to the percentage of incompatibilities (full match for 23 SNPs; 1-3 mm and >3 mm). An exception was the association between 1-3 mismatches at the composite of SNPs C13193/T14952/T19588 with the development of aGVHD (P = 0.012) and with grades III-IV of this disease (P = 0.004). Conclusion: Our data are not consistent with the hypothesis that disparities in C4A/C4B SNPs increase the risks of post-HSCT adverse effects for the endpoints investigated in this study.
Subject(s)
Humans , Child , Adolescent , Adult , Genes, MHC Class I , Complement C4a , Complement C4b , Hematopoietic Stem Cell Transplantation , Polymorphism, Single Nucleotide , Polymorphism, Genetic , Mortality , Graft vs Host DiseaseABSTRACT
BACKGROUND: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. RESULTS: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. CONCLUSIONS: We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.
Subject(s)
Humans , Male , Female , Ethnicity/genetics , Indians, South American/genetics , Polymorphism, Single Nucleotide/genetics , Population Groups/genetics , Genetics, Population/organization & administration , Saliva , Genetic Markers/genetics , Chile , Phylogeography , Genotyping Techniques , Gene Frequency/genetics , GenotypeABSTRACT
ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.
Subject(s)
Humans , Female , Adult , Polymorphism, Genetic/genetics , Premenopause/blood , Postmenopause/blood , Aryldialkylphosphatase/blood , Eating , Cross-Sectional Studies , Premenopause/metabolism , Postmenopause/metabolism , Aryldialkylphosphatase/genetics , GenotypeABSTRACT
El maíz (Zea mays L.) posee un genoma complejo y una amplia diversidad genética. La información de caracteres fenotípicos y marcadores moleculares en su conjunto provee una mejor descripción e interpretación de la variabilidad genética. El objetivo del trabajo fue estimar la diversidad genética y caracterizar fenotípicamente un panel de 291 líneas de maíz de CIMMYT. Las líneas corresponden a ocho grupos establecidos de acuerdo a su adaptación ambiental y origen geográfico. Éstas se evaluaron fenotípicamente por medio de nueve caracteres agro-morfológicos en tres ambientes del sur de la provincia de Córdoba, Argentina. El intervalo antesis-estigma (IAE) presentó la mayor variabilidad fenotípica. El 40% de las líneas de maíz registraron un IAE menor a cinco días, indicando buena adaptación a los ambientes de evaluación. La estructura poblacional dada por los subgrupos de adaptación ambiental es sólo un factor menor que contribuye a la variabilidad fenotípica del panel estudiado. El análisis de componentes principales (ACP) permitió obtener el ordenamiento fenotípico y el genotípico, mientras que el análisis de procrustes generalizado indicó un consenso del 60% entre ambos ordenamientos para el total de líneas. El consenso entre el ordenamiento obtenido con caracteres agro-morfológicos y con marcadores moleculares indica desequilibrio de ligamiento entre los SNPs y los genes que controlan los caracteres agro-morfológicos. Los resultados muestran una amplia diversidad genética en el germoplasma evaluado, lo que sugiere que esta colección de líneas es un recurso importante para impulsar ganancias genéticas futuras en los programas de mejoramiento de maíz de Argentina.
CIMMYT maize inbred lines (CMLs) are freely distributed to breeding programs around the world. Better information on phenotypic and genotypic diversity may provide guidance to breeders on how to use more efficiently the CMLs in their breeding programs. In this study a group of 291 CIMMYT maize inbred lines, was phenotyped by nine agro-morphological traits in south Córdoba, Argentina and genotyped using 18,082 SNPs. Based on the geographic information and the environmental adaptation, 291 CMLs were classified into eight subgroups. Anthesis-silking interval (IAE) was the trait with higher phenotypic diversity. A 40% of maize inbred lines, with IAE less than five days, show a good adaptation to growing conditions in south Córdoba, Argentina. The low phenotypic variation explained by environmental adaptation subgroups indicates that population structure is only a minor factor contributing to phenotypic diversity in this panel. Principal component analysis (ACP) allowed us to obtain phenotypic and genotypic orderings. Generalized procrustes analysis (APG) indicated a 60% consensus between both data type from the total panel of maize lines. In each environmental adaptation subgroup, the APG consensus was higher. This result, which might indicate linkage disequilibrium between SNPs markers and the genes controlling these agro-morphological traits, is promising and could be used as an initial tool in the identification of Quantitative Trait Loci (QTL). Information on genetic diversity, population structure and phenotypic diversity in local environments will help maize breeders to better understand how to use the current CIMMYT maize inbred lines group.
ABSTRACT
BACKGROUND: A total of 62,591 cowpea expressed sequence tags (ESTs) were BLAST aligned to the whole-genome sequence of barrel medic (Medicago truncatula) to develop conserved intron scanning primers (CISPs). The efficacy of the primers was tested across 10 different legumes and on different varieties of cowpea, chickpea, and pigeon pea. Genetic diversity was assessed using the same primers on different cowpea genotypes. Singlenucleotide polymorphisms (SNPs) were detected, which were later converted to length polymorphism markers for easy genotyping. CISPs developed in this study were used in tagging resistance to bacterial leaf blight disease in cowpea. RESULTS: A total of 1262 CISPs were designed. The single-copy amplification success rates using these primers on 10 different legumes and on different varieties of cowpea, chickpea, and pigeon pea were approximately 60% in most of the legumes except soybean (47%) and peanut (37%). Genetic diversity analysis of 35 cowpea genotypes using 179 CISPs revealed 123 polymorphic markers with PIC values ranging from 0.05 to 0.59. Potential SNPs identified in cowpea, chickpea, and pigeon pea were converted to PCR primers of various sizes for easy genotyping. Using the markers developed in this study, a genetic linkage map was constructed with 11 linkage groups in cowpea. QTL mapping with 194 F3 progeny families derived from the cross C-152 × V-16 resulted in the identification of three QTLs for resistance to bacterial leaf blight disease. Conclusions: CISPs were proved to be efficient markers to identify various other marker classes like SNPs through comparative genomic studies in lesser studied crops and to aid in systematic sampling of the entire genome for well-distributed markers at low cost
Subject(s)
Genome, Plant , Genomics/methods , Medicago truncatula/genetics , Polymerase Chain Reaction , Chromosome Mapping , Expressed Sequence Tags , Polymorphism, Single Nucleotide , Genomics , Quantitative Trait Loci , Fabaceae/geneticsABSTRACT
Introducción. El cáncer colorrectal es una carga para la salud pública en Colombia y el mundo. Estudios de asociación genética han identificado regiones cromosómicas asociadas a esta enfermedad, mostrando riesgo variable entre poblaciones, debido a la historia demográfica y la ancestría genética. Objetivo. Estudiar el riesgo que aportan 20 marcadores al cáncer colorrectal en Colombia, empleando 955 casos y 972 controles del consorcio CHIBCHA, analizando conjuntamente el efecto de la ancestría genética global y local. Metodología. Las muestras se genotipificaron usando microarreglos Axyom Affymetrix LAT y CUSTOME, para obtener los genotipos genómicos globales, incluyendo 20 SNPs de riesgo. Los análisis estadísticos se realizaron en PLINK (asociaciones), ADMIXTURE (ancestría global), Elai (ancestría local) y R (modelos logísticos). Resultados. Once regiones cromosómicas resultaron asociadas presentando ORs entre 1.14 y 1.41 (p<0.05): 18q21.1, 19q13.11, 10p14, 14q.2.2, 20p12.3, 8q23.3, 6p21.2, 15q13.3 y 8q24.21. Una mayor ancestría europea se asoció con el riesgo a nivel global (OR=3.016, IC 95%:1.162-7.894, p=0.00325), y a nivel cromosómico local se detectaron las regiones 6q23.2 (ORajustado=1.378, IC95%: 1.202-1.580, Pajustado=4.2e-6) y 4p13 (ORajustado=1.301, IC95%:1.137-1.489; Pajustado=0.00013). Conclusiones. La ancestría podría considerarse un factor en la explicación de la susceptibilidad en Colombia, indicando que la mezcla genética de origen amerindio y europeo, influye en la estructura poblacional y explicaría las diferencias en la incidencia del CCR entre poblaciones latinas y europeas.
Introduction: Colorectal cancer is a public health burden in the world and Colombia. Recent genome wide association studies have identified chromosomal regions associated with the disease, depicting variable risk between populations, owing to the demographic history and genetic ancestry. Objective: We aimed to study the colorectal cancer risk in Colombia provided for 20 genetic markers, by using 955 cases and 972 controls from the CHIBCHA consortium, in the context of global and local genetic ancestry. Methodology: The samples were genotyped using Axyom Affymetrix LAT and CUSTOME array in order to obtain the global genome genotypes including 20 risk SNPs. Statistical analysis was performed in PLINK (associations), ADMIXTURE (global ancestry), Elai (local ancestry) and R language (logistic models). Results: Eleven chromosomal regions were associated with ORs ranging between 1.14-1.41 (p<0.05): 18q21.1, 19q13.11, 10p14, 14q.2.2, 20p12.3, 8q23.3, 6p21.2, 15q13.3 y 8q24.21. On average, a higher global European ancestry was associated with colorectal cancer risk (OR=3.016, IC 95%:1.162-7.894, p=0.00325). At the local chromosomal level two regions presented a significant increment of European ancestry 6q23.2 (OR adjusted=1.378, CI95%: 1.202-1.580, p adjusted =4.2e-6) and 4p13 (OR adjusted =1.301, CI95%:1.137-1.489; p adjusted =0.00013). Conclusions: Genetic ancestry can be considered as a relevant factor for the colorectal cancer susceptibility in Colombia. Both Native American and European ancestry are accounting for the most part of population structure in the sample we studied, which could explain the differences for the colorectal cancer incidence between Latin American and European populations.
Subject(s)
Humans , Genetic Association Studies , Colorectal Neoplasms , Colombia , Genetic Predisposition to DiseaseABSTRACT
O transtorno por uso de álcool (TUA) é influenciado pela genética, principalmente na metabolização do etanol. Os genes da álcool desidrogenase (ADH1B/ADH1C), enzima que transforma o etanol, apresentam SNPs (single nucleotide polymorphisms) que resultam em isoenzimas com diferentes taxas catalíticas. Estudos demonstraram que os SNPs Arg48His, Arg370Cys, Arg272Gln e Ile350Val contribuem para o TUA. Este artigo revisou os estudos que investigaram SNPs em ADH1B (Arg48His/Arg370Cys) e ADH1C (Arg272Gln/Ile350Val), bem como avaliou as variações nas frequências alélicas desses genes e a influência no TUA nas diferentes populações no mundo. As frequências alélicas dos polimorfismos foram comparadas pelos testes qui-quadrado de Pearson e exato de Fisher (p < 0,05). O SNP Arg48His confere proteção para o TUA em euroamericanos, latino-americanos, europeus, brasileiros, asiáticos e australianos. O SNP Arg370Cys confere proteção para o TUA em afrodescendentes. Os SNPs Arg272Gln e Ile350Val predispõem o TUA principalmente em europeus. Os SNPs Arg48His, Arg370Cys e Arg272Gln/Ile350Val foram mais frequentes em amostras de leste-asiáticos (69,7%), africanos (19,1%) e europeus (40,5%), respectivamente (p < 0,01). Os diferentes alelos dos genes ADH1B/ADH1C devido a SNPs têm uma importante contribuição no TUA. As frequências desses alelos variam conforme a população, resultando em diferentes efeitos no TUA. (AU)
Alcohol use disorder (AUD) is influenced by genetics, especially in the metabolism of ethanol. The ethanol dehydrogenase genes (ADH1B/ADH1C), which convert ethanol, have single nucleotide polymorphisms (SNPs) that result in isoenzymes with different catalytic rates. Studies have shown that the Arg48His, Arg370Cys, Arg272Gln, and Ile350Val SNPs contribute to AUD. This article reviewed the studies that investigated SNPs in ADH1B (Arg48His/Arg370Cys) and ADH1C (Arg272Gln/Ile350Val) and evaluated variations in the allele frequencies of these genes and their influence on AUD in different populations worldwide. The allele frequencies of the polymorphisms were compared by Pearson's chi-square and Fisher's exact tests (p < 0.05). The Arg48His SNP provides protection against AUD in Euro-Americans, Latin Americans, Europeans, Brazilians, Asians, and Australians. The Arg370Cys SNP provides protection against AUD in Afro-descendants. The Arg272Gln and Ile350Val SNPs predispose to AUD mainly in Europeans. The Arg48His, Arg370Cys, and Arg272Gln/Ile350Val SNPs were more frequent in East Asians (69.7%), Africans (19.1%), and Europeans (40.5%), respectively (p < 0.01). The different alleles of the ADH1B/ADH1C genes due to SNPs make an important contribution to AUD. The frequencies of these alleles vary among different populations, resulting in different effects on AUD..(AU)