Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients

Background and Aims Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Methods Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Results Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). Conclusions This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes

Farelo da raiz integral de mandioca em dietas de frangos de corte tipo caipira #

The aim this work was to evaluate cassava root meal inclusion levels in diets of free-range broiler chickens on performance, carcass yield, parts yield and functional properties of the meat. 384 male chickens of ISA S757-N strain (naked neck) were distributed in a completely randomized design with four treatment and four replicates of 24 birds each. The treatments were 0%, 20%, 40% and 60% of FRIM (cassava root meal) in the total ration. The trial period was divided into three rearing phases: initial (1 to 28 days of age), growth (29 to 56 days of age) and fattening (57 to 84 days of age). Final body weight (PF), weight gain (WG), feed intake, feed conversion and liveability were evaluated. At 84 th day, carcass, breast, thigh + upper thigh, wing, back and abdominal fat yield were obtained. Breast meat was used to determi- ne the pH, water holding capacity (CRA) and cooking loss (PPC) too. The shank and breast skin color scores were determined by visual comparison. The results were submitted to analysis of variance, analysis of regression and averages were compared by Tukey’s test to 5% of probability. The analysis of variance found a significant difference between treatments for BW and WG, only at the phase of 1 to 28 days of age. There was a linear increased in BW and WG when the CRM inclusion level increased in feed. There were no significant differences between the treatments for the variables of carcass yield, cuts yield, pH, CRA and PPC. The use of FRIM in the diets of free- range broiler chickens promoted linear reduction in the shank and breast skin colors with the increase of the inclusion level of this ingredient in the feed. The FRIM can be used in the diets of free- range broiler chickens in the proportion of 60% of total ration without resulting in worst performan- ce, carcass yield, cuts yield and functional properties of the meat, however it promotes shank and breast skin no coloration.O objetivo do trabalho foi avaliar níveis de inclusão de farelo da raiz integral de mandioca, em dietas de frangos de corte tipo caipira, sobre o desempenho, os rendimentos de carcaça, de cortes e as propriedades funcionais da carne. Foram distribuídos 384 pintainhos machos da linhagem ISA S757-N (pescoço pelado) em um delineamento inteiramente casualizado com quatro tratamentos e quatro repetições de 24 aves cada. Os tratamentos foram 0%, 20%, 40% e 60% de FRIM (farelo da raiz integral de mandioca) na ração total. O período experimental foi dividido em três fases de criação: inicial (1 a 28 dias de idade), crescimento (29 a 56 dias de idade) e engorda (57 a 84 dias de idade). Foram obtidos o peso corporal final (PF), o ganho de peso (GP), consumo de ração, conversão alimentar e viabilidade. Aos 84 dias foram obtidos os rendimentos de carcaça, peito, coxa+sobrecoxa, asa, dorso gordura abdo- minal e das carnes de peito das aves foram determinados o pH, capacidade de retenção de água (CRA) e perda de peso por cozimento (PPC).Por comparação visual, foram determinados os escores para as cores de pele de canela e de peito. Os resultados foram submetidos à análise de variância, à análise de regressão e as médias foram comparadas pelo teste de Tukey a 5% de probabilidade. A análise de variância detectou diferença significativa entre os tratamentos para PF e GP, somente na fase de 1 a 28 dias de idade. Foi verificado aumento linear para PF e GP à medida que se aumentou o nível de inclusão de FRIM na ração. Não existiram diferenças significa- tivas entre os tratamentos para as variáveis de rendimento de carcaça, de cortes, pH, CRA e PPC. A utilização do FRIM nas dietas de frangos de corte tipo caipira promoveu redução linear na coloração das peles da canela e do peito das aves com o aumento do nível de inclusão desse ingre- diente nas rações. O farelo da raiz integral de mandioca pode ser utilizado nas dietas de frangos de corte tipo caipira na proporção de 60% da ração total sem prejudicar o desempenho, os rendimentos de carcaça, de corte e as propriedades funcionais da carne, no entanto promove descoloração das peles de canela e peito