Risk of cancer in family members of patients with lynch-like syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk

Identification and characterization of putative targets of VEGETATIVE1/FULc, a key regulator of development of the compound inflorescence in pea and related legumes

Inflorescence architecture contributes to essential plant traits. It determines plant shape, contributing to morphological diversity, and also determines the position and number of flowers and fruits produced by the plant, thus influencing seed yield. Most legumes have compound inflorescences, where flowers are produced in secondary inflorescences (I2), formed at the flanks of the main primary inflorescence (I1), in contrast to simple inflorescences of plants like Arabidopsis, in which flowers are directly formed on the I1. The pea VEGETATIVE1/FULc (VEG1) gene, and its homologs in other legumes, specify the formation of the I2 meristem, a function apparently restricted to legumes. To understand the control of I2 development, it is important to identify the genes working downstream of VEG1. In this study, we adopted a novel strategy to identify genes expressed in the I2 meristem, as potential regulatory targets of VEG1. To identify pea I2-meristem genes, we compared the transcriptomes of inflorescence apices from wild-type and mutants affected in I2 development, such as proliferating inflorescence meristems (pim, with more I2 meristems), and veg1 and vegetative2 (both without I2 meristems). Analysis of the differentially expressed genes using Arabidopsis genome databases combined with RT-qPCR expression analysis in pea allowed the selection of genes expressed in the pea inflorescence apex. In situ hybridization of four of these genes showed that all four genes are expressed in the I2 meristem, proving our approach to identify I2-meristem genes was successful. Finally, analysis by VIGS (virus-induced gene silencing) in pea identified one gene, PsDAO1, whose silencing leads to small plants, and another gene, PsHUP54, whose silencing leads to plants with very large stubs, meaning that this gene controls the activity of the I2 meristem. PsHUP54-VIGS plants are also large and, more importantly, produce large pods with almost double the seeds as the control. Our study shows a new useful strategy to isolate I2-meristem genes and identifies a novel gene, PsHUP54, which seems to be a promising tool to improve yield in pea and in other legumes

Evidence of the role of QTL epistatic interactions in the increase of melon fruit flesh content during domestication

Cultivated melon was domesticated from wild melons, which produce small fruits with non-edible fruit flesh. The increase in fruit flesh is one of the major domestication achievements in this species. In previous work, a quantitative trait locus (QTL) on chromosome 6 (paqt6.1) linked to fruit flesh content was detected in a cross between cultivated ("Piel de Sapo", PS) and wild (Ames 24294, TRI) accessions. The QTL was introgressed into the PS background, generating the TRI_6-3 introgression line (IL) that confirmed the effects of paqt6.1. The primary objective of this work was to fine-map paqt6.1 as the first step for the map-based cloning. Two different approaches were carried out; however, the results were not consistent, precluding the fine mapping of paqt6.1. TRI_6-3 and other related ILs were genotyped by genotyping-by-sequencing, finding additional introgressions in other chromosomes. In an F2 population from TRI_6-3-x-PS, we found an epistatic interaction between paqt6.1 and another locus on chromosome 11. The interaction was verified in advanced populations, suggesting that the effects of paqt6.1 are conditioned by the allelic composition at another locus in chromosome 11. Both loci should have TRI alleles to reduce the flesh content in the PS background. The implications on the history of melon domestication are discussed

A DSP implementation of an AOM and its application to defects detection in textile material

This paper explains a method of defects detection in textile material using a DSP. This Supervised Learning method will allow the detection of defects in anyone of the phases of production. An algorithm of pattern classification based on minimum distance is used to carry out this method. Scalar distance in an Associative Orthogonal Memory (AOM network) is used to provide a measure of the angle which form the 2 compared vectors too. In our system, we can appreciate that the method doesn't require an excessive processing time, so we can implement it for real time processing. Other advantage of the system is that it is applied to different types of clothes and defects (In general, other approaches are centred in only one type of defect). In the other hand, our algorithms produce rates of success around 94%. These results are quite encouraging if we keep in mind that it has been analysed some complex cloth types (such as lined cloth). To finish, and since the results obtained both in error rate and in execution times have been quite good, the application of this method can be very advantageous, moreover knowing that the development environment used is relatively simple

Risk of cancer in family members of patients with Lynch-Like Syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk

Risk of cancer in family members of patients with lynch-like syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56–2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67–4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44–2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26–5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk