Lung adenocarcinoma promotion by air pollutants.

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development. Here we propose that environmental particulate matter measuring ≤2.

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease.

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.

Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts.

Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints.

Recombination affects allele-specific expression of deleterious variants in human populations.

How the genetic composition of a population changes through stochastic processes, such as genetic drift, in combination with deterministic processes, such as selection, is critical to understanding how phenotypes vary in space and time. Here, we show how evolutionary forces affecting selection, including recombination and effective population size, drive genomic patterns of allele-specific expression (ASE). Integrating tissue-specific genotypic and transcriptomic data from 1500 individuals from two different cohorts, we demonstrate that ASE is less often observed in regions of low recombination, and loci in high or normal recombination regions are more efficient at using ASE to underexpress harmful mutations.

Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues.

Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control.

Aims/hypothesis: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk.

Methods: We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies.

The genome of the water strider Gerris buenoi reveals expansions of gene repertoires associated with adaptations to life on the water.

Background: Having conquered water surfaces worldwide, the semi-aquatic bugs occupy ponds, streams, lakes, mangroves, and even open oceans. The diversity of this group has inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders our ability to more thoroughly investigate the molecular mechanisms underlying the processes of adaptation and diversification within this group.

Interruption points in the wing gene regulatory network underlying wing polyphenism evolved independently in male and female morphs in Cardiocondyla ants.

Wing polyphenism in ants, which produces a winged female queen caste and a wingless female worker caste, evolved approximately 150 million years ago and has been key to the remarkable success of ants. Approximately 20 million years ago, the myrmicine ant genus Cardiocondyla evolved an additional wing polyphenism among males producing two male morphs: wingless males that fight to enhance mating success and winged males that disperse. Here we show that interruption of rudimentary wing-disc development in larvae of the ant Cardiocondyla obscurior occurs further downstream in the network in wingless males as compared with wingless female workers.

Aberrant expression impacts the pan-cancer genomic landscape.

The binding of PRDM9 to chromatin is a key step in the induction of DNA double-strand breaks associated with meiotic recombination hotspots; it is normally expressed solely in germ cells. We interrogated 1879 cancer samples in 39 different cancer types and found that is unexpectedly expressed in 20% of these tumors even after stringent gene homology correction. The expression levels of in tumors are significantly higher than those found in healthy neighboring tissues and in healthy nongerm tissue databases.

Social regulation of a rudimentary organ generates complex worker-caste systems in ants.

The origin of complex worker-caste systems in ants perplexed Darwin and has remained an enduring problem for evolutionary and developmental biology. Ants originated approximately 150 million years ago, and produce colonies with winged queen and male castes as well as a wingless worker caste. In the hyperdiverse genus Pheidole, the wingless worker caste has evolved into two morphologically distinct subcastes-small-headed minor workers and large-headed soldiers.

Gene-by-environment interactions in urban populations modulate risk phenotypes.

Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to comprehensively assess the interactions between 1.

Allele-specific expression reveals interactions between genetic variation and environment.

Identifying interactions between genetics and the environment (GxE) remains challenging. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on associations between environmental variables and allele-specific expression. Combining whole-blood RNA-seq with extensive environmental annotations collected from 922 human individuals, we identified 35 GxE interactions, compared with only four using standard GxE interaction testing.

Impact of the X Chromosome and sex on regulatory variation.

The X Chromosome, with its unique mode of inheritance, contributes to differences between the sexes at a molecular level, including sex-specific gene expression and sex-specific impact of genetic variation. Improving our understanding of these differences offers to elucidate the molecular mechanisms underlying sex-specific traits and diseases. However, to date, most studies have either ignored the X Chromosome or had insufficient power to test for the sex-specific impact of genetic variation.

Past climate change on Sky Islands drives novelty in a core developmental gene network and its phenotype.

Background: A fundamental and enduring problem in evolutionary biology is to understand how populations differentiate in the wild, yet little is known about what role organismal development plays in this process. Organismal development integrates environmental inputs with the action of gene regulatory networks to generate the phenotype. Core developmental gene networks have been highly conserved for millions of years across all animals, and therefore, organismal development may bias variation available for selection to work on.

Eco-evo-devo: the time has come.

The major goal of ecological evolutionary developmental biology, also known as "eco-evo-devo," is to uncover the rules that underlie the interactions between an organism's environment, genes, and development and to incorporate these rules into evolutionary theory. In this chapter, we discuss some key and emerging concepts within eco-evo-devo. These concepts show that the environment is a source and inducer of genotypic and phenotypic variation at multiple levels of biological organization, while development acts as a regulator that can mask, release, or create new combinations of variation.

Awareness of standard precautions for 4439 healthcare professionals in 34 institutions in France.

Objective: The study objective was to assess the awareness of standard precautions (SP) among healthcare professionals, 1 year after the latest national guidelines were issued.

Methods: A multicenter cross-sectional survey was conducted in 34 volunteer institutions in 2010. Data was collected using an anonymous and self-administered questionnaire.

The genome sequence of the leaf-cutter ant Atta cephalotes reveals insights into its obligate symbiotic lifestyle.

Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies.

Draft genome of the red harvester ant Pogonomyrmex barbatus.

We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing.

Development and transferability of apricot and grape EST microsatellite markers across taxa.

EST microsatellite markers were developed in apricot (Prunus armeniaca L.) and grape (Vitis vinifera L.).

[Risk of deep infection in first-intention total hip replacement. Evaluation concerning a continuous series of 790 cases].

Objective: Deep infections of the operative site is a rare but serious complication of first intention total hip arthroplasties. French data on infections are sparse. We studied the incidence, characteristics and potential risk factors for these infections in a consecutive series of 790 total hip arthroplasties performed as first intention implantations in a University Hospital in France.