Análise citogenética de híbridos entre Triticum durum x Aegilops tauschii com potencial uso em programas de melhoramento genético de trigo.

Editores técnicos: Joseani Mesquita Antunes, Ana Lídia Variani Bonato, Márcia Barrocas Moreira Pimentel

CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

Contrasting results exist on the association between CTLA-4 rs231775 and acute rejection in kidney transplant recipients. We herein conducted an updated systematic review with meta-analysis and trial sequential analysis (TSA) to clarify this relationship and to establish whether the current evidence is sufficient to draw firm conclusions. In addition, noteworthiness of significant pooled odds ratios (ORs) was estimated by false positive report probability (FPRP). A comprehensive search was performed through PubMed, Web of Knowledge, Cochrane Library and Open Grey up to October 2019. Fifteen independent cohorts, including a total of 5,401 kidney transplant recipients, were identified through the systematic review. Overall, no association was detected with the allelic (OR 1.07, 95% CI 0.88\u20131.30, P = 0.49), dominant (OR 0.94, 95% CI 0.73\u20131.22, P = 0.66) or the recessive (OR 1.18, 95% CI 0.97\u20131.43, P = 0.096) model of CTLA-4 rs231775. In each genetic model, the cumulative Z-curve in TSA crossed the futility boundary and entered the\ua0futility\ua0area. In addition, none of the significant genetic comparisons detected in the subsequent and sensitivity analyses or in previously reported meta-analyses were found to be noteworthy by FPRP. In conclusion, this study provides strong evidence that CTLA-4 rs231775 is not a clinically-relevant genetic risk determinant of acute rejection after renal transplantation

Caracterização citogenética clássica e molecular de trigos brasileiros.

Editores técnicos: Joseani Mesquita Antunes, Ana Lídia Variani Bonato, Márcia Barrocas Moreira Pimentel

DPYD IVS14+1G>A and 2846A>T genotyping for the prediction of severe fluoropyrimidine-related toxicity: a meta-analysis.

Aim: In the present study we conducted a systematic review and meta-analysis of published data to quantify the impact of the DPYD IVS14+1G>A and 2846A>T variants on the risk of fluoropyrimidine-related toxicities and to determine sensitivity and specificity testing for DPYD variants. Methods: Relevant studies were identified through PubMed and Web of Knowledge databases, studies included were those published up until to May 2012. Study quality was assessed according to the HuGENET guidelines and Strengthening the Reporting of Genetic Association (STREGA) recommendations. Results: Random-effects meta-analysis provided evidence that carriers of DPYD IVS14+1G>A are at higher risk of ≥3 degrees of overall grade toxicity, hematological toxicity, mucositis and diarrhea. In addition, a strong association was also found between carriers of the DPYD 2846T allele and overall grade ≥3 toxicity or grade ≥3 diarrhea. An inverse linear relationship was found in prospective studies between the odds ratio of DPYD IVS14+1G>A and the incidence of overall grade ≥3 toxicity, indicating an higher impact in cohorts in which the incidence of severe toxicity was lower. Conclusion: The results of this meta-analysis confirm clinical validity of DPYD IVS14+1G>A and 2846A>T as risk factors for the development of severe toxicities following fluoropyrimidine treatment. Furthermore, the sensitivity and specificity estimates obtained could be useful in establishing the cost-effectiveness of testing for DPYD variants. Original submitted 4 March 2013; Revision submitted 17 June 2013

Pathogenesis of eosinophilic esophagitis: A comprehensive review of the genetic and molecular aspects

Eosinophilic esophagitis (EoE) is a relatively new condition described as an allergicmediated disease of the esophagus. Clinically, it is characterized by dysphagia, food impaction, and reflux-like symptoms. Multiple genome-wide association studies (GWAS) have been conducted to identify genetic loci associated with EoE. The integration of numerous studies investigating the genetic polymorphisms in EoE and the Mendelian diseases associated with EoE are discussed to provide insights into the genetic risk of EoE, notably focusing on CCL26 and CAPN14. We focus on the genetic loci investigated thus far, and their classification according to whether the function near the loci is known. The pathophysiology of EoE is described by separately presenting the known function of each cell and molecule, with the major contributors being eosinophils, Th2 cells, thymic stromal lymphopoietin (TSLP), transforming growth factor (TGF)-β1, and interleukin (IL)-13. This review aims to provide detailed descriptions of the genetics and the comprehensive pathophysiology of EoE

Targeted next-generation sequencing for the identification of genetic predictors of radiation-induced late skin toxicity in breast cancer patients: A preliminary study

Normal tissue radiosensitivity is thought to be influenced by an individual’s genetic back-ground. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we carried out targeted next-generation sequencing of germline DNA samples from 48 breast cancer patients with extreme late skin toxicity phenotypes, consisting of 24 cases with grade 2–3 subcutaneous fibrosis and/or grade 2–3 telangiectasia (LENT-SOMA scales) and 24 controls with grade 0 fibrosis and grade 0 telangiectasia. In this exploratory study, a total of five single-nucleotide variants (SNVs) located in three genes (TP53, ERCC2, and LIG1) reached nominal levels of statistical significance (p C, Pro72Arg) in the replication cohort had an effect (OR per C allele: 1.52, 95%CI: 0.82–2.83, p = 0.186) in the same direction as in the exploratory cohort (OR per C allele: 4.70, 95%CI: 1.51–14.6, p = 0.007) and was found be nominally associated to the risk of radiation-induced late skin toxicity in the overall combined cohort (OR per C allele: 1.79, 95%CI: 1.06–3.02, p = 0.028). These results raise the possibility of an association between TP53 rs1042522 and risk of radiation-induced late skin toxicity in breast cancer patients; however, large replication studies are warranted for conclusive evidence

Ocorrência de micronúcleos e inferência da instabilidade genética em acessos de trigos sintéticos.

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Estabilidade genética em genótipos de trigo estimada pela viabilidade polínica.

Objetivou-se estimar a estabilidade genética de 170 genótipos de trigo por meio da viabilidade polínica. Os genótipos foram provenientes do Banco Ativo de Germoplasma e dos ensaios de Valor e Cultivo e Uso da Embrapa Trigo, no período 2011 a 2013. Foram coletadas espigas em pré-antese, fixadas em Carnoy 3:1 e armazenadas em álcool 70%. As lâminas citológicas foram preparadas pela técnica de ?Squash? e corante carmin acético 1%. As análises foram em microscopia ótica, com três repetições e 1500 células/genótipo. Os resultados indicaram que 98% dos genótipos apresentaram viabilidade polínica acima de 95%, identificados como estáveis. Quanto às anormalidades, foram observados grãos de pólens vazios na maioria dos genótipos, mas com incidência muito baixas, não significativas