Genetic susceptibility, residential radon, and lung cancer in a radon prone area

INTRODUCTION: Radon exposure has been classified as the second cause of lung cancer, after tobacco, and the first in never smokers. GSTM1 and GSTT1 genes deletion increase the risk of lung cancer. We aim to know whether the risk of lung cancer because of residential radon is modulated by these genetic polymorphisms. METHODS: Hospital-based, case-control study where cases had confirmed lung cancer. Cases and controls did not have previous neoplasm and were older than 30. Controls attended hospital for noncomplex surgery. We analyzed the results for the whole sample and separately for never/light smokers and moderate/heavy smokers. RESULTS: Seven-hundred and ninety-two participants were analyzed. GSTM1 and GSTT1 deletion conferred an odds ratio (OR) of 1.38 (95% confidence interval [CI] 0.93-2.04) and 1.13 (95% CI 0.70-1.82), respectively. Individuals with GSTM1 present and residential radon concentrations higher than 148 Bq/m had an OR of 1.48 (95% CI 0.73-3.00), whereas those with GSTM1 deleted had an OR of 2.64 (95% CI 1.18-5.91) when compared with participants with GSTM1 present and radon concentrations below 50 Bq/m3. Similar results were observed for GSTT1 deletion. These results were basically the same for the moderate/heavy smokers' subgroup. CONCLUSIONS: The absence of GSTM1 and GSTT1 genes increases the risk of lung cancer because of radon exposure. These genes might modulate the carcinogenic pathway of alpha radiation. Further studies are warranted analyzing this association in never smokers

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Genetic Diversity in Wheat: Analysis using Diversity Arrays Technology (DArT) in bread and durum wheats

With increasing demands on the quality and quantity of food required now and in the future, improvements to current agriculture practices are required. Increased food production requires utilisation of more agricultural land, pushing crops into non- traditional areas. The need for advances in agricultural technologies are not only required for current crop varieties, but for new varieties with increased tolerance to environmental stresses. Technological improvement means better crop yields and reduced land, water, fertilizer and pesticide use. Diversity Arrays Technology (DArT) was used to study wheat diversity, specifically to identify polymorphic markers between various wheat cultivars for use in marker- assisted breeding programs. The hybridisation based technology was used to analyse various bread and durum wheat cultivars for increased understanding of genomic diversity. Analysis shows that DArT is able to discriminate between tissue samples from wheat cultivars grown under various environmental stresses with polymorphic markers identified between samples treated with differing salt, light and temperature conditions. Epigenetic diversity was analysed through methylation detection using DArT to identify a list of candidate polymorphic markers. Markers were identified using the methylation sensitive restriction enzyme McrBC to generate control and treated targets. Diversity through cultivar exploration, looking at breeding experiments between cultivars with phenotypic extremes to examine salt tolerance versus in-tolerance using DArT produced a recombinant inbred line genetic linkage map. Bulk segregant analysis was also used to group phenotypic samples. Candidate markers were identified between cultivars that can be used to genotyping tetraploid and hexaploid wheat cultivars for germplasm identification. In addition, the identification of trait-linked molecular markers, such as salt resistance, plant breeders can genotype individual plants and populations of cultivars to determine the most suitable cultivar to plant that best complements to its local environment. This eliminates the need for multiple planting cycles to optimize crop selections, and gives the plant breeder the highest possible chance for crop success (yield, quality, performance and cost)

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection

Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome ( approximately 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

Funder: Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Ministry of Culture, Education and University Planning, Government of Galicia); doi: https://doi.org/10.13039/501100008425Funder: Ministerio de Educación, Cultura y Deporte (Ministry of Education, Culture and Sports, Spain); doi: https://doi.org/10.13039/501100003176Funder: EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council); doi: https://doi.org/10.13039/100010663Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Korea Health Industry Development Institute (KHIDI); doi: https://doi.org/10.13039/501100003710Funder: Danish Medical Research CouncilFunder: NIHFunder: Associazione Italiana Contro le Leucemie-Linfomi e MielomaFunder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Abstract: About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors