SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints

Background: Genomic disorders are caused by copy number changes that may exhibit recurrent breakpoints processed by nonallelic homologous recombination. However, region-specific disease-associated copy number changes have also been observed which exhibit non-recurrent breakpoints. The mechanisms underlying these non-recurrent copy number changes have not yet been fully elucidated. Results: We analyze large NF1 deletions with non-recurrent breakpoints as a model to investigate the full spectrum of causative mechanisms, and observe that the

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Production of Υ(nS) mesons in Pb+Pb and pp collisions at 5.02 TeV

A measurement of the production of vector bottomonium states, Υ ( 1S ) , Υ ( 2S ) , and Υ ( 3S ) , in Pb + Pb and p p collisions at a center-of-mass energy per nucleon pair of 5.02 TeV is presented. The data correspond to integrated luminosities of 1.38 nb − 1 of Pb + Pb data collected in 2018, 0.44 nb − 1 of Pb + Pb data collected in 2015, and 0.26 fb − 1 of p p data collected in 2017 by the ATLAS detector at the Large Hadron Collider. The measurements are performed in the dimuon decay channel for transverse momentum p μ μ T < 30 GeV , absolute rapidity | y μ μ | < 1.5 , and Pb + Pb event centrality 0–80%. The production rates of the three bottomonium states in Pb + Pb collisions are compared with those in p p collisions to extract the nuclear modification factors as functions of event centrality, p μ μ T , and | y μ μ | . In addition, the suppression of the excited states relative to the ground state is studied. The results are compared with theoretical model calculations

Learning and transfer in signaling games

Learning, Learning transfer, Cross-game learning, Signaling games, Experiment, C72, C92, D82, L12,

Renal dysfunction during tenofovir use in a regional cohort of HIV-infected individuals in the Asia-Pacific

10.1371/journal.pone.0161562PLoS ONE118e016156