Drosophila Toxicogenomics: genetic variation and sexual dimorphism in susceptibility to 4-Methylimidazole.

Background: 4-methylimidazole is a ubiquitous and potentially carcinogenic environmental toxicant. Genetic factors that contribute to variation in susceptibility to its toxic effects are challenging to assess in human populations. We used the Drosophila melanogaster Genetic Reference Panel (DGRP), a living library of natural genetic variation, to identify genes with human orthologs associated with variation in susceptibility to 4-methylimidazole.

The genetic basis of incipient sexual isolation in .

Speciation is a fundamental evolutionary process but the genetic changes accompanying speciation are difficult to determine since true species do not produce viable and fertile offspring. Partially reproductively isolated incipient species are useful for assessing genetic changes that occur prior to speciation. from Zimbabwe, Africa are partially sexually isolated from other populations whose males have poor mating success with Zimbabwe females.

The genetic basis of variation in mating behavior.

Mating behavior is an essential fitness trait. We used the inbred, sequenced lines of the Genetic Reference Panel (DGRP) to gain insights into the evolution of mating success and to evaluate the overlap in genetic architecture of mating behavior between the sexes. We found significant genetic variation for mating success when DGRP males and females from the same line were mated together, and when DGRP males and females were mated to an unrelated strain of the opposite sex.

Pleiotropy, epistasis and the genetic architecture of quantitative traits.

Pleiotropy (whereby one genetic polymorphism affects multiple traits) and epistasis (whereby non-linear interactions between genetic polymorphisms affect the same trait) are fundamental aspects of the genetic architecture of quantitative traits. Recent advances in the ability to characterize the effects of polymorphic variants on molecular and organismal phenotypes in human and model organism populations have revealed the prevalence of pleiotropy and unexpected shared molecular genetic bases among quantitative traits, including diseases. By contrast, epistasis is common between polymorphic loci associated with quantitative traits in model organisms, such that alleles at one locus have different effects in different genetic backgrounds, but is rarely observed for human quantitative traits and common diseases.

Perspectives on the Drosophila melanogaster Model for Advances in Toxicological Science.

The use of Drosophila melanogaster for studies of toxicology has grown considerably in the last decade. The Drosophila model has long been appreciated as a versatile and powerful model for developmental biology and genetics because of its ease of handling, short life cycle, low cost of maintenance, molecular genetic accessibility, and availability of a wide range of publicly available strains and data resources. These features, together with recent unique developments in genomics and metabolomics, make the fly model especially relevant and timely for the development of new approach methodologies and movements toward precision toxicology.

Perceptions of antimicrobial stewardship: identifying drivers and barriers across various professions in Canada utilizing a one health approach.

Introduction: As antimicrobial resistance (AMR) represents a substantial threat to the efficacy of available antimicrobial options, it is important to understand how to implement effective and practical mitigation efforts, including antimicrobial stewardship (AMS), across human, animal, and environmental sectors.

Methods: A mixed-methods questionnaire was distributed virtually to attendees of the virtual One Health Antimicrobial Stewardship Conference (March 10-12, 2021) and their professional networks. Respondents ( = 81) were largely from the veterinary (75%) or human (19%) health sectors.

Natural genetic variation in a dopamine receptor is associated with variation in female fertility in .

Fertility is a major component of fitness but its genetic architecture remains poorly understood. Using a full diallel cross of 50 Genetic Reference Panel inbred lines with whole genome sequences, we found substantial genetic variation in fertility largely attributable to females. We mapped genes associated with variation in female fertility by genome-wide association analysis of common variants in the fly genome.

Genetic and genomic analyses of Drosophila melanogaster models of chromatin modification disorders.

Switch/sucrose nonfermentable (SWI/SNF)-related intellectual disability disorders (SSRIDDs) and Cornelia de Lange syndrome are rare syndromic neurodevelopmental disorders with overlapping clinical phenotypes. SSRIDDs are associated with the BAF (Brahma-Related Gene-1 associated factor) complex, whereas CdLS is a disorder of chromatin modification associated with the cohesin complex. Here, we used RNA interference in Drosophila melanogaster to reduce the expression of six genes (brm, osa, Snr1, SMC1, SMC3, vtd) orthologous to human genes associated with SSRIDDs and CdLS.

Genetic and Genomic Analyses of Models of Chromatin Modification Disorders.

Switch/Sucrose Non-Fermentable (SWI/SNF)-related intellectual disability disorders (SSRIDDs) and Cornelia de Lange syndrome are rare syndromic neurodevelopmental disorders with overlapping clinical phenotypes. SSRIDDs are associated with the BAF ( Associated Factor) complex, whereas CdLS is a disorder of chromatin modification associated with the cohesin complex. Here, we used RNA interference in to reduce expression of six genes () orthologous to human genes associated with SSRIDDs and CdLS.

The genetic architecture of behavioral canalization.

Behaviors are components of fitness and contribute to adaptive evolution. Behaviors represent the interactions of an organism with its environment, yet innate behaviors display robustness in the face of environmental change, which we refer to as 'behavioral canalization'. We hypothesize that positive selection of hub genes of genetic networks stabilizes the genetic architecture for innate behaviors by reducing variation in the expression of interconnected network genes.

Pleiotropic fitness effects of a Drosophila odorant-binding protein.

Insect odorant-binding proteins (OBPs) are members of a rapidly evolving multigene family traditionally thought to facilitate chemosensation. However, studies on Drosophila have shown that members of this family have evolved functions beyond chemosensation, as evident from their expression in reproductive tissues and the brain. Previous studies implicated diverse functions of Obp56h, a member of the largest gene cluster of the D.

Pleiotropic fitness effects of the lncRNA Uhg4 in Drosophila melanogaster.

Background: Long noncoding RNAs (lncRNAs) are a diverse class of RNAs that are critical for gene regulation, DNA repair, and splicing, and have been implicated in development, stress response, and cancer. However, the functions of many lncRNAs remain unknown. In Drosophila melanogaster, U snoRNA host gene 4 (Uhg4) encodes an antisense long noncoding RNA that is host to seven small nucleolar RNAs (snoRNAs).

Gregor Mendel's legacy in quantitative genetics.

Gregor Mendel's discovery of the laws of segregation and independent assortment and his inference of the existence of non-mendelian interactions between loci remain at the heart of today's explorations of the genetic architecture of quantitative traits.

Modulation of the Drosophila transcriptome by developmental exposure to alcohol.

Background: Prenatal exposure to ethanol can cause fetal alcohol spectrum disorder (FASD), a prevalent, preventable pediatric disorder. Identifying genetic risk alleles for FASD is challenging since time, dose, and frequency of exposure are often unknown, and manifestations of FASD are diverse and evident long after exposure. Drosophila melanogaster is an excellent model to study the genetic basis of the effects of developmental alcohol exposure since many individuals of the same genotype can be reared under controlled environmental conditions.

Ibrutinib as a potential therapeutic for cocaine use disorder.

Cocaine use presents a worldwide public health problem with high socioeconomic cost. No current pharmacologic treatments are available for cocaine use disorder (CUD) or cocaine toxicity. To explore pharmaceutical treatments for tthis disorder and its sequelae we analyzed gene expression data from post-mortem brain tissue of individuals with CUD who died from cocaine-related causes with matched cocaine-free controls (n = 71, M = 39.

Prevalence, Risk Factors, and Antimicrobial Resistance Profile of Respiratory Pathogens Isolated From Suckling Beef Calves to Reprocessing at the Feedlot: A Longitudinal Study.

Here, we investigated the prevalence and risk factors for the presence of , and in the respiratory tract of calves from the spring processing to the reprocessing at feedlots. Additionally, we characterized, phenotypically and genotypically, the antimicrobial resistance (AMR) profile of the four species. Calves from 22 cow-calf operations were enrolled in the study ( = 30 calves per operation) and sampled by deep nasopharyngeal swabs at three time points: spring processing, weaning, or induction into feedlots, and at reprocessing at the feedlot.

Knowledge Gaps in the Understanding of Antimicrobial Resistance in Canada.

Current limitations in the understanding and control of antimicrobial resistance (AMR) in Canada are described through a comprehensive review focusing on: (1) treatment optimization; (2) surveillance of antimicrobial use and AMR; and (3) prevention of transmission of AMR. Without addressing gaps in identified areas, sustained progress in AMR mitigation is unlikely. Expert opinions and perspectives contributed to prioritizing identified gaps.

Epistasis for head morphology in Drosophila melanogaster.

Epistasis-gene-gene interaction-is common for mutations with large phenotypic effects in humans and model organisms. Epistasis impacts quantitative genetic models of speciation, response to natural and artificial selection, genetic mapping, and personalized medicine. However, the existence and magnitude of epistasis between alleles with small quantitative phenotypic effects are controversial and difficult to assess.

Physiological and metabolomic consequences of reduced expression of the Drosophila brummer triglyceride Lipase.

Disruption of lipolysis has widespread effects on intermediary metabolism and organismal phenotypes. Defects in lipolysis can be modeled in Drosophila melanogaster through genetic manipulations of brummer (bmm), which encodes a triglyceride lipase orthologous to mammalian Adipose Triglyceride Lipase. RNAi-mediated knock-down of bmm in all tissues or metabolic specific tissues results in reduced locomotor activity, altered sleep patterns and reduced lifespan.

Developmental Alcohol Exposure in Drosophila: Effects on Adult Phenotypes and Gene Expression in the Brain.

Fetal alcohol exposure can lead to developmental abnormalities, intellectual disability, and behavioral changes, collectively termed fetal alcohol spectrum disorder (FASD). In 2015, the Centers for Disease Control found that 1 in 10 pregnant women report alcohol use and more than 3 million women in the USA are at risk of exposing their developing fetus to alcohol. is an excellent genetic model to study developmental effects of alcohol exposure because many individuals of the same genotype can be reared rapidly and economically under controlled environmental conditions.