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1.
Braz. j. oral sci ; 20: e211654, jan.-dez. 2021. ilus
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1254524

RESUMO

Grade C periodontitis in youngers is characterized by a severe form of periodontitis, and IL10 rs6667202 single nucleotide polymorphism (SNP) has been described as an important feature in this disease etiology. Aim: This study aimed to evaluate, in vivo, the functionality of IL10 rs6667202 SNP on IL-10 gingival fluid levels. Methods: Thirty patients with Perio4C were selected, 15 with the IL10 AA genotype (rs6667202) and 15 with AC/CC genotypes. The gingival fluid was collected from two sites with probing depth ≥ 7 mm and bleeding on probing, and two healthy sites. The IL-10 concentration was determined by Luminex/MAGpix platform. Results: In deep pockets, the IL10 AA genotype presented a lower concentration of IL-10 when compared with AC or CC genotypes (p<0.05). In shallow pockets, no difference between groups was seen (p>0.05). Conclusion: IL10 rs6667202 SNP decreases the production of IL-10 in crevicular fluid, potentially affecting this disease progression


Assuntos
Humanos , Masculino , Feminino , Periodontite Agressiva , Interleucina-10 , Polimorfismo de Nucleotídeo Único
2.
Genes (Basel) ; 12(6)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201032

RESUMO

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.


Assuntos
Receptor do Fator Ativador de Células B/genética , COVID-19/etiologia , COVID-19/genética , Feminino , Frequência do Gene , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Índice de Gravidade de Doença
3.
Urol Clin North Am ; 48(3): 283-296, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210485

RESUMO

The identification and characterization of alterations in prostate cancer (PCa)-predisposing genes can help to inform screening strategies in undiagnosed men and treatment options in men in both the clinically localized and in the metastatic setting. This review provides an overview of the genetic basis underlying hereditary predisposition to PCa, the current role of genetics and PCa risk assessment, and how genetic risk factors affect aggressiveness and lethality of PCa.


Assuntos
Predisposição Genética para Doença , Neoplasias da Próstata/genética , Fatores Etários , Biomarcadores Tumorais/genética , Progressão da Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etnologia , Fatores de Risco
4.
Urol Clin North Am ; 48(3): 373-386, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210492

RESUMO

Prostate cancer represents a significant health care burden in the United States due to its incidence, treatment-related morbidity, and cancer-specific mortality. The burden begins with prostate-specific antigen screening, which has been subject to controversy due to concerns of overdiagnosis and overtreatment. Advancements in molecular oncology have provided evidence for the inherited predisposition to prostate cancer, which could improve individualized, risk-adapted approaches to screening and mitigate the harms of routine screening. This review presents the current evidence for the genetic basis of prostate cancer and novel genetically informed, risk-adapted screening strategies for prostate cancer.


Assuntos
Predisposição Genética para Doença , Programas de Rastreamento/métodos , Neoplasias da Próstata/genética , Adulto , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Mutação em Linhagem Germinativa , Humanos , Imageamento por Ressonância Magnética , Masculino , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/sangue
5.
Urol Clin North Am ; 48(3): 411-423, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210495

RESUMO

There remains a paucity of data related to germline genetic alterations predisposing patients to prostate cancer. Recent data suggest that African American, Hispanic, and Asian and Pacific Islander men exhibit genetic alterations in both highly penetrant germline genes, including BRCA1/2, ATM, and CHEK2, and the mismatch repair genes associated with Lynch syndrome, as well as low-penetrant single-nucleotide polymorphisms. However, cohort sizes remain small in many studies limiting the ability to determine clinical significance, appropriate risk stratification, and treatment implications in these diverse populations.


Assuntos
Predisposição Genética para Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteína BRCA1 , Quinase do Ponto de Checagem 2 , Neoplasias Colorretais Hereditárias sem Polipose/etnologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Medição de Risco
6.
Front Cell Infect Microbiol ; 11: 656393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307188

RESUMO

Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).


Assuntos
Antivirais , Interleucinas , Antivirais/uso terapêutico , Brasil , Quimioterapia Combinada , Genótipo , Humanos , Imunidade Inata , Interferon-alfa/uso terapêutico , Interferons , Interleucinas/genética , Polietilenoglicóis/uso terapêutico , Polimorfismo de Nucleotídeo Único , Proteínas Recombinantes , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral
7.
Front Cell Infect Microbiol ; 11: 669394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307193

RESUMO

Signal transducer and activator of transcription-3 (STAT3) plays an important role in biological balance. Our and others previous studies implied that STAT3 had a great effect on fast-acting innate immunity against tuberculosis (TB). We hypothesized that stat3 SNP down-regulation of STAT3 leads to a change in susceptibility to TB in humans. To test this hypothesis, we investigated STAT3 SNPs using SNP scan™ technique in a case-control study of TB patients (n = 470) and HC subjects (n = 356), and then conducted functional studies of them using cellular models. We found that SNPs in STAT3 3`-UTR of rs1053004 TT and rs1053005 AA genotypes or T-A haplotype were associated with susceptibility to TB or TB severity. While the TT/AA genotype correlated with the low constitutive expression of stat3 and IL-17A in PBMC, the variant stat3 of rs1053004-rs1053005 T-A haplotype indeed reduced stat3 expression in reporter assays. Interestingly, host PBMC expressing the rs1053005 AA genotype and low constitutive stat3 exhibited the reduced ability to mount fast-acting innate immunity against mycobacterial infection in cellular models. Finally, mechanistic experiments showed that the STAT3 down-regulation broadly depressed STAT3 downstream anti-mycobacterial activities involving VDR-related CAMP pathway as well as IL-32, iNOS and autophagy mechanisms, leading to an enhanced mycobacterial infection. The findings of this study suggest that low constitutive stat3 derived from the TT/AA genotype/T-A haplotype acts to down-regulate STAT3, depressing multiple anti-mycobacterial pathways/mechanisms downstream, which leads to an enhanced mycobacterial infection or TB in high-risk individuals.


Assuntos
Leucócitos Mononucleares , Tuberculose , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT3/genética , Tuberculose/genética
8.
J Int Med Res ; 49(7): 3000605211033219, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34311603

RESUMO

OBJECTIVE: To investigate whether GSTA1, GSTO2, and GSTZ1 are relevant to an increased risk of amyotrophic lateral sclerosis (ALS) in a Chinese population. METHODS: In this study, 143 sporadic ALS (sALS) patients (83 men, 60 women) and 210 age- and sex-matched healthy subjects were enrolled. Blood samples were collected by venipuncture. Genomic DNA was isolated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) according to the manufacturer's instructions. The potential associations between ALS and GSTA1, GSTO2, and GSTZ1 polymorphisms were estimated using chi-squared analysis and unconditional logistic regression. RESULTS: The D allele and genotype frequencies of GSTO2 were increased in sALS patients compared with healthy subjects, indicating that the GSTO2 DD genotype was associated with an increased risk of sALS (odds ratio [OR] = 3.294, 95% confidence interval [CI] = 1.039-10.448). However, a significant association between the DD genotype and the risk of sALS was evident in men only (OR = 7.167, 95% CI = 1.381-37.202). CONCLUSION: This study revealed that the D allele and genotype frequencies of GSTO2 were increased in sALS patients. The GSTO2 DD genotype was associated with an increased risk of sALS in men in a Chinese population.


Assuntos
Esclerose Amiotrófica Lateral , Predisposição Genética para Doença , Glutationa Transferase , Esclerose Amiotrófica Lateral/genética , Grupo com Ancestrais do Continente Asiático/genética , China , Feminino , Genótipo , Glutationa Transferase/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
9.
BMC Genomics ; 22(1): 573, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34311701

RESUMO

BACKGROUND: Chinese indigenous rabbits have distinct characteristics, such as roughage resistance, stress resistance and environmental adaptability, which are of great significance to the sustainable development of the rabbit industry in China. Therefore, it is necessary to study the genetic diversity and population structure of this species and develop genomic resources. RESULTS: In this study, we used restriction site-associated DNA sequencing (RAD-seq) to obtain 1,006,496 SNP markers from six Chinese indigenous rabbit breeds and two imported rabbit breeds. Jiuyishan and Fujian Yellow rabbits showed the highest nucleotide diversity (π) and decay of linkage disequilibrium (LD), as well as higher observed heterozygosity (Ho) and expected heterozygosity (He), indicating higher genetic diversity than other rabbits. The inbreeding coefficient (FIS) of New Zealand rabbits and Belgian rabbits was higher than that of other rabbits. The neighbour-joining (NJ) tree, principal component analysis (PCA), and population structure analysis of autosomes and Y chromosomes showed that Belgian, New Zealand, Wanzai, Sichuan White, and Minxinan Black rabbits clustered separately, and Fujian Yellow, Yunnan Colourful, and Jiuyishan rabbits clustered together. Wanzai rabbits were clearly separated from other populations (K = 3), which was consistent with the population differentiation index (FST) analysis. The selection signature analysis was performed in two populations with contrasting coat colours. With Sichuan White and New Zealand rabbits as the reference populations and Minxinan Black and Wanzai rabbits as the target populations, 408, 454, 418, and 518 genes with a selection signature, respectively, were obtained. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the genes with a selection signature. The results showed that the genes with a selection signature were enriched in the melanogenesis pathway in all four sets of selection signature analyses. CONCLUSIONS: Our study provides the first insights into the genetics and genomics of Chinese indigenous rabbit breeds and serves as a valuable resource for the further effective utilization of the species.


Assuntos
Genética Populacional , Polimorfismo de Nucleotídeo Único , Coelhos , Animais , Cruzamento , China , Genômica , Nova Zelândia , Análise de Sequência de DNA
10.
BMC Genomics ; 22(1): 575, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315401

RESUMO

BACKGROUND: Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits. RESULTS: We re-sequenced the entire coding region and 3000 bp of 5' and 3' flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5' flanking region, two in 5' untranslated region (UTR), two in exon 1, five in 3' UTR, and three in 3' flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007). CONCLUSIONS: In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.


Assuntos
Ácidos Graxos , Leite , Animais , Bovinos/genética , Feminino , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Serotonina
11.
World J Gastroenterol ; 27(25): 3863-3876, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34321850

RESUMO

BACKGROUND: The association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease (NAFLD) requires further confirmation. In addition, it is still unknown whether PPARGC1A rs8192678 is associated with hepatic histological features in NAFLD in the Chinese population. AIM: To investigate the interaction between PPARGC1A rs8192678 and nonalcoholic steatohepatitis (NASH), and whether this polymorphism is associated with hepatic histological features. METHODS: Fifty-nine patients with liver biopsy-proven NAFLD and 93 healthy controls were recruited to a cohort representing the Chinese Han population. The SAF (steatosis, activity, and fibrosis) scoring system was used for hepatic histopathological evaluation. The polymorphisms of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 were genotyped. The intrahepatic mRNA expression of PPARGC1A was evaluated by real-time polymerase chain reaction. RESULTS: Thirty-seven patients with NAFLD had NASH, of which 12 were nonobese. The PPARGC1A rs8192678 risk A allele (carrying GA and AA genotypes) had the lowest P value in the dominant model; the odds ratio (OR) for NAFLD was 2.321 [95% confidence interval (CI): 1.121-4.806]. After adjusting for age, sex, and the PNPLA3 rs738409 risk G allele, the PPARGC1A rs8192678 A allele was a risk factor for NAFLD (OR 2.202, 95%CI: 1.030-4.705, P = 0.042). The genetic analysis showed that patients with NAFLD, moderate-to-severe steatosis (S2-3), and Activity 2-4 (A ≥ 2) were more likely to carry A in PPARGC1A rs8192678 (OR 5.000, 95%CI: 1.343-18.620, P = 0.012; and OR 4.071, 95%CI: 1.076-15.402, P = 0.031). The multivariate logistic regression analysis showed that PPARGC1A rs8192678 risk A allele was also independently associated with S2-3, A ≥ 2, and NASH (OR 6.190, 95%CI: 1.508-25.410, P = 0.011; OR 4.506, 95%CI 1.070-18.978, P = 0.040; and OR 6.337, 95%CI: 1.135-35.392, P = 0.035, respectively) after adjusting for age, sex, body mass index, and PNPLA3 rs738409 risk G allele. The results also showed that this polymorphism was associated with nonobese NASH (OR 22.000, 95%CI: 1.540-314.292, P = 0.021). The intrahepatic expression of PPARGC1A mRNA was significantly lower in the group of patients who carried the risk A allele (P = 0.014). CONCLUSION: The PPARGC1A rs8192678 risk A allele is associated with NAFLD, and with S2-3, A ≥ 2 and NASH in NAFLD patients, independent of PNPLA3 rs738409, and may be associated with nonobese NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Predisposição Genética para Doença , Humanos , Lipase/genética , Fígado/metabolismo , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único
12.
Nutrients ; 13(6)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34200102

RESUMO

Transcription factor-7-like 2 (TCF7L2) is one of the most important susceptibility genes for type 2 diabetes mellitus (T2DM). The aim of our cross-sectional population-based study was to analyze whether daily macronutrient intake may influence the effects of the TCF7L2 rs7901695 genotype on glucose homeostasis and obesity-related parameters. We recruited 810 participants (47.5% men and 52.5% women), 18-79 years old (mean age, 42.1 (±14.5) years), who were genotyped for the common TCF7L2 rs7901695 single-nucleotide polymorphism (SNP), and anthropometric measurements, body composition, body fat distribution (visceral (VAT) and subcutaneous adipose tissue (SAT) content), blood glucose and insulin concentrations after fasting and during OGTTs, and HbA1c were assessed. The VAT/SAT ratio, HOMA-IR (homeostatic model assessment of insulin resistance), HOMA-B (homeostatic model assessment of ß-cell function), and CIR30 (corrected insulin response) were calculated. The daily macronutrient intake was evaluated based on 3-day food-intake diaries. Daily physical activity was evaluated based on a validated questionnaire. We performed ANOVA or Kruskal-Wallis tests, and multivariate linear regression models were created to evaluate the effects of dietary macronutrient intake on glucose homeostasis and obesity-related parameters in carriers of the investigated genotypes. This study was registered at ClinicalTrials.gov as NCT03792685. The TT-genotype carriers stratified to the upper protein intake quantiles presented higher HbA1c levels than the CT- and CC-genotype participants in the same quantiles (p = 0.038 and p = 0.022, respectively). Moreover, we observed higher HOMA-IR (p = 0.014), as well as significantly higher blood glucose and insulin concentrations, during the OGTTs for those in the upper quantiles, when compared to subjects from the lower quantiles of protein intake, while the CC-genotype carriers presented significantly lower HbA1c (p = 0.033) and significantly higher CIR30 (p = 0.03). The linear regression models revealed that an increase in energy derived from proteins in TT carriers was associated with higher HbA1c levels (ß = 0.37 (95% CI: 0.01-0.74, p = 0.05)), although, in general, carrying the TT genotype, but without considering protein intake, showed an opposite tendency-to lower HbA1c levels (ß = -0.22 (95% CI: 0.47 to -0.01, p = 0.05). Among the subjects stratified to the lower quantile of carbohydrate intake, the TT-genotype individuals presented higher HbA1c (p = 0.041), and the CC-genotype subjects presented higher VAT (p = 0.033), lower SAT (p = 0.033), and higher VAT/SAT ratios (p = 0.034). In both the CC- and TT-genotype carriers, we noted higher VAT (p = 0.012 and p = 0.0006, respectively), lower SAT (p = 0.012 and p = 0.0006, respectively) and higher VAT/SAT ratios (p = 0.016 and p = 0.00062, respectively) when dietary fat provided more than 30% of total daily energy intake, without any differences in total body fat content. Our findings suggest that associations of the common TCF7L2 SNP with glucose homeostasis and obesity-related parameters may be dependent on daily macronutrient intake, which warrants further investigations in a larger population, as well as interventional studies.


Assuntos
Ingestão de Alimentos , Glucose/metabolismo , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adolescente , Adulto , Idoso , Glicemia/análise , Composição Corporal , Distribuição da Gordura Corporal , Estudos Transversais , Ingestão de Alimentos/fisiologia , Feminino , Genótipo , Homeostase/fisiologia , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição/fisiologia , Adulto Jovem
13.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203967

RESUMO

A substantial proportion of subjects with autosomal recessive retinitis pigmentosa (arRP) or Usher syndrome type II (USH2) lacks a genetic diagnosis due to incomplete USH2A screening in the early days of genetic testing. These cases lack eligibility for optimal genetic counseling and future therapy. USH2A defects are the most frequent cause of USH2 and are also causative in individuals with arRP. Therefore, USH2A is an important target for genetic screening. The aim of this study was to assess unscreened or incompletely screened and unexplained USH2 and arRP cases for (likely) pathogenic USH2A variants. Molecular inversion probe (MIP)-based sequencing was performed for the USH2A exons and their flanking regions, as well as published deep-intronic variants. This was done to identify single nucleotide variants (SNVs) and copy number variants (CNVs) in 29 unscreened or partially pre-screened USH2 and 11 partially pre-screened arRP subjects. In 29 out of these 40 cases, two (likely) pathogenic variants were successfully identified. Four of the identified SNVs and one CNV were novel. One previously identified synonymous variant was demonstrated to affect pre-mRNA splicing. In conclusion, genetic diagnoses were obtained for a majority of cases, which confirms that MIP-based sequencing is an effective screening tool for USH2A. Seven unexplained cases were selected for future analysis with whole genome sequencing.


Assuntos
Análise Custo-Benefício , Éxons/genética , Proteínas da Matriz Extracelular/genética , Sondas Moleculares/metabolismo , Sítios de Splice de RNA/genética , Retinite Pigmentosa/genética , Análise de Sequência de DNA , Síndromes de Usher/genética , Sequência de Bases , Variações do Número de Cópias de DNA/genética , Deleção de Genes , Humanos , Polimorfismo de Nucleotídeo Único/genética , Retinite Pigmentosa/economia , Síndromes de Usher/economia
14.
Trop Anim Health Prod ; 53(3): 395, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245361

RESUMO

BACKGROUND: Assigning animals to their corresponding breeds through breed informative single-nucleotide polymorphisms (SNPs) is required in many fields. For instance, it is used in the traceability and the authentication of meat and other livestock products. SNPs' information for several pork breeds are now accessible thanks to the availability of dense SNP chips. These SNP chips cover a large number of molecular markers distributed across the entire genome. To identify the pork breed from a sample of industrial meat, one must analyze a large panel of genetic markers depending on the SNP chip used. The analysis of such large datasets requires intensive work. This leads to the idea of creating less dense chips of breed informative markers based on a reduced number of SNPs. Therefore, the analysis of the data emanating from the genotyping of these reduced chips will require less time and effort. AIM: The objective of this study is to find the most informative SNPs for the discrimination between four pig breeds, namely Duroc, Landrace, Large White, and Pietrain. METHOD: The Illumina Porcine 60 k SNP chip was used to genotype SNPs distributed all over the individuals' genomes. Firstly, we used three different statistical approaches for feature selection: (i) principal component analysis (PCA), (ii) least absolute shrinkage and selection operator (LASSO), and (iii) random forest (RF). These three approaches identified three sets of SNPs; each set corresponds to one approach. Then, we combined the results of the three methods by setting up a final panel containing the SNPs which appear on the three sets altogether. RESULTS: Separately, each method resulted in a panel with the corresponding most discriminating SNPs. The PCA, the LASSO, and the random forest with Boruta algorithm highlighted 28,816, 50, and 286 SNPs, respectively. The number of SNPs selected by PCA is high compared to Boruta and LASSO because PCA chooses the variables while preserving as much information about the data as possible. The only downside of LASSO regression is that among a group of correlated variables, LASSO tends to select only one variable and ignore the others regardless of their importance. Contrarily to LASSO, the Boruta algorithm considers the interdependence between SNPs and selects informative variables even if they are correlated and have the same effect. The three panels shared 23 SNPs; the distribution of the individuals according to these SNPs showed a grouping of individuals of each breed in well-defined clusters without any overlapping. CONCLUSIONS: The biological pathways represented by 23 breed informative SNPs resulted by the combination of PCA, LASSO, and Boruta should be explored in further analysis. The results provided by our study are promising for further applications of this method in other livestock animals.


Assuntos
Genética Populacional , Polimorfismo de Nucleotídeo Único , Animais , Marcadores Genéticos , Genótipo , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Suínos/genética
15.
Cent Eur J Public Health ; 29(2): 130-133, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34245553

RESUMO

OBJECTIVES: Vitamin D is a fat-soluble, prohormone vitamin that is important especially for bone mineralization and skeletal health. In recent years, vitamin D deficiency appeared as a worldwide problem, affecting many people in different ways including the Northern Cypriot population. The deficiency might be caused by the lack of exposure to sunlight, diet low in vitamin D, sedentary lifestyle, and also due to some genetic variations in the vitamin D receptor (VDR) gene. METHODS: In this study, four common VDR polymorphisms and associations with vitamin D deficiency in the Turkish Cypriot population between ages 18-40 and working in office conditions was studied by PCR- RFLP analysis. RESULTS: rs2228570 C>T variant was shown to be significantly associated with low serum vitamin D levels in the studied population. CONCLUSION: Together with the effect of rs2228570 C>T variant in the VDR gene, it is thought that the lifestyle changes in the Turkish Cypriot population might have caused the increased frequency of vitamin D deficiency in the young professionals.


Assuntos
Polimorfismo de Nucleotídeo Único , Deficiência de Vitamina D , Adolescente , Adulto , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Fragmento de Restrição , Seleção Genética , Vitamina D , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/genética , Adulto Jovem
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 647-651, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247369

RESUMO

OBJECTIVE: To explore the genetic etiology for a fetus with congenital orofacial cleft. METHODS: Single nucleotide polymorphism microarray (SNP array) was carried out on skin tissues sampled from the fetus following induced abortion for the detection of copy number variation (CNVs). Pathogenicity of the candidate gene was validated through experiment. RESULTS: SNP array revealed that the fetus has carried a hemizygous 9.23Mb deletion at Xq21.31-q22.1(91 063 807-100 293 555), which was inherited from its mother. The region contained 13 OMIM genes and 1 ncRNA coding gene(MIR548M). Inhibiting of the expression of the MIR548M gene in oral epithelial celllines has resulted in up-regulation of the expression of SUMO1 gene which was known to involve in the pathogenesis of orofacial cleft. CONCLUSION: Dosage insufficiency of the MIR548M gene may underlie the etiology of orofacial cleft in this fetus.


Assuntos
Fenda Labial , Fissura Palatina , MicroRNAs , Fenda Labial/genética , Fissura Palatina/genética , Variações do Número de Cópias de DNA/genética , Feminino , Feto , Humanos , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Gravidez , Proteína SUMO-1
17.
Tumour Biol ; 43(1): 129-140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219681

RESUMO

OBJECTIVES: Single nucleotide variants (SNVs) in vascular endothelial growth factor A (VEGFA) and VEGFA receptor (KDR) genes confer different inherited abilities in angiogenesis (AG) pathway. We aimed in the present study to evaluate influence of six VEGFA and four KDR SNVs in clinical features and survival of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: One hundred and sixty-eight DLBCL patients diagnosed between June 2009-September 2014 were enrolled in the study. Patients were homogeneously treated with R-CHOP. Genotypes were identified in genomic DNA by real-time polymerase chain reaction. RESULTS: Patients with VEGFA -634CC and +936CT or TT genotypes were at increased risk of showing grade III / IV toxicities and not achieving complete remission with treatment, and shorter event-free and overall survival were seen in patients with VEGFA -1154GA or AA genotype and VEGFA ATAGCC haplotype. CONCLUSION: Our data suggest that inherited abnormalities in AG's gene modulate clinical features and prognosis of DLBCL patients homogeneously treated with R-CHOP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/patologia , Neovascularização Patológica/patologia , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Prednisona/administração & dosagem , Prognóstico , Estudos Prospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagem
18.
BMC Plant Biol ; 21(1): 305, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193036

RESUMO

BACKGROUND: Natural variations derived from both evolutionary selection and genetic recombination, presume to have important functions to respond to various abiotic stresses, which could be used to improve drought tolerance via genomic selection. RESULTS: In the present study, the NAC-encoding gene of ZmNAC080308 was cloned and sequenced in 199 inbred lines in maize. Phylogenetic analysis showed that ZmNAC080308 is closely clusteredinto the same group with other well-known NAC genes responding to improve drought tolerance. In total, 86 SNPs and 47 InDels were identified in the generic region of ZmNAC080308, 19 of these variations were associated with GY (grain yield) in different environments. Nine variations in the 5'-UTR region of ZmNAC080308 are closely linked, they might regulate the gene expression and respond to improve GY under drought condition via Sp1-mediated transactivation. Two haplotypes (Hap1 and Hap2) identified in the, 5'-UTR region using the nine variations, and Hap2 containing insertion variants, exhibited 15.47 % higher GY under drought stress condition. Further, a functional marker was developed to predict the drought stress tolerance in a US maize inbred line panel. Lines carrying Hap2 exhibited > 10 % higher GY than those carrying Hap1 under drought stress condition. In Arabidopsis, overexpression ZmNAC080308 enhanced drought tolerance. CONCLUSIONS: ZmNAC080308 is an important gene responding to drought tolerance, a functional marker is developed for improving maize drought tolerance by selecting this gene.


Assuntos
Secas , Variação Genética , Proteínas de Plantas/genética , Sementes/crescimento & desenvolvimento , Estresse Fisiológico/genética , Zea mays/genética , Zea mays/fisiologia , Regiões 5' não Traduzidas/genética , Sequência de Aminoácidos , Arabidopsis/genética , Núcleo Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Marcadores Genéticos , Genótipo , Desequilíbrio de Ligação/genética , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Polimorfismo de Nucleotídeo Único/genética , Plântula/metabolismo , Frações Subcelulares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198853

RESUMO

In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving ≥50% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by α-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipase/genética , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Idoso , Feminino , Regulação da Expressão Gênica/genética , Hepacivirus/genética , Hepatócitos/virologia , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Gotículas Lipídicas/virologia , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/virologia , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos
20.
J Contemp Dent Pract ; 22(3): 248-252, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210923

RESUMO

AIM AND OBJECTIVE: This study is conducted to find the association of BMP2 (bone morphogenic protein 2) gene variant rs1005464 and rs15705 with skeletal class I crowding cases. MATERIALS AND METHODS: Blood samples from 60 subjects who visited the Department of Orthodontics and Dentofacial Orthopaedics, D.A.P.M.R.V. Dental College, Bengaluru, were taken after written informed consent. These were divided into two groups: group A with 30 subjects having skeletal class I bases with crowding and group B with 30 subjects having skeletal class I bases without visible crowding or spacing (±2 mm). Around 2 mL of venous blood sample was procured from cases and controls after careful examination. All the samples were then subjected to polymerase chain reaction followed by DNA sequencing and capillary electrophoresis. BMP2 rs1005464 and rs15705 gene variants were assessed and Z-Test was used for statistical analysis. RESULT: GG (p = 0.001) and CC (p = 0.0024) genotype of BMP2 gene variant rs1005464 and rs15705, respectively, are significantly associated with skeletal class I crowding cases. CONCLUSION: This study concludes that BMP2 variants rs1005464 and rs15705 can be used as genetic markers for skeletal class I bases having crowding. CLINICAL SIGNIFICANCE: Predisposing genetic markers BMP2 can be identified prior and this would help in predicting the probability of potential crowding in the future and this would help in early prevention and intervention of crowding.


Assuntos
Má Oclusão , Polimorfismo de Nucleotídeo Único , Proteína Morfogenética Óssea 2/genética , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética
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