Genetic dissection of complex, polygenic trait variation is a key goal medical and evolutionary genetics. Attempts to identify genetic variants underlying complex traits have been plagued by low mapping resolution in traditional linkage studies, an inability that cumulatively explain the bulk standing genome-wide association studies (GWAS). Thus, much heritability remains unexplained for most traits. Here we describe novel, freely available resource Drosophila community consisting two sets...

Abstract It has been hypothesized that individually-rare hidden structural variants (SVs) could account for a significant fraction of variation in complex traits. Here we identified more than 20,000 euchromatic SVs from 14 Drosophila melanogaster genome assemblies, which ~40% are invisible to high specificity short-read genotyping approaches. common, with 31.5% diploid individuals harboring SV genes larger 5kb, and 24% multiple 10kb. minor allele frequencies rarer amino acid polymorphisms,...

The Drosophila Synthetic Population Resource (DSPR) is a newly developed multifounder advanced intercross panel consisting of >1600 recombinant inbred lines (RILs) designed for the genetic dissection complex traits. Here, we describe inference underlying mosaic founder structure full set RILs from dense semicodominant restriction-site-associated DNA (RAD) markers and use simulations to explore how variation in marker density sequencing coverage affects inference. For given effort, more...

Here we present computational machinery to efficiently and accurately identify transposable element (TE) insertions in 146 next-generation sequenced inbred strains of Drosophila melanogaster. The panel lines use our study is composed from a pair genetic mapping resources: the Genetic Reference Panel (DGRP) Synthetic Population Resource (DSPR). We identified 23,087 TE these lines, which 83.3% are found only one line. There marked differences distribution elements over genome, with TEs at...

ABSTRACT Herpes simplex virus type 1 (HSV-1) strain KOS has been extensively used in many studies to examine HSV-1 replication, gene expression, and pathogenesis. Notably, is known be less pathogenic than the first sequenced genome of HSV-1, 17. To understand genotypic differences between other phenotypically distinct strains we viral KOS. When comparing 17, there are at least 1,024 small nucleotide polymorphisms (SNPs) 172 insertions/deletions (indels). The observed will likely provide...

Modern genetic mapping is plagued by the "missing heritability" problem, which refers to discordance between estimated heritabilities of quantitative traits and variance accounted for mapped causative variants. One major potential explanation missing heritability allelic heterogeneity, in there are multiple variants at each gene with only a fraction having been identified. The majority genome-wide association studies (GWAS) implicitly assume that single SNP can explain all locus. However, if...

Abstract A quantitative trait locus (QTL) genetic analysis of morphological and reproductive traits distinguishing the sibling species Drosophila simulans D. sechellia was carried out in a backcross design, using 38 markers with an average spacing 8.4 cM. The direction QTL effects for size posterior lobe consistent across identified QTL, indicating directional selection this trait. Directional also appears to have acted on testis length, that sexual may influenced many traits, although other...

Natural populations exhibit a great deal of interindividual genetic variation in the response to toxins, exemplified by variable clinical efficacy pharmaceutical drugs humans, and evolution pesticide resistant insects. Such can result from several phenomena, including metabolic detoxification xenobiotic, differential sensitivity molecular target toxin. Our goal is genetically dissect xenobiotics, characterize naturally-segregating polymorphisms that modulate toxicity. Here, we use Drosophila...

Abstract Animals in nature are frequently challenged by toxic compounds, from those that occur naturally plants as a defense against herbivory, to pesticides used protect crops. On exposure such xenobiotic substances, animals mount transcriptional response, generating detoxification enzymes and transporters metabolize remove the toxin. Genetic variation this response can lead susceptibility of different genotypes effects given xenobiotic. Here we use Drosophila melanogaster dissect genetic...

Abstract Work in many systems has shown large-scale changes gene expression during aging. However, studies employ just two, arbitrarily-chosen timepoints at which to measure expression, and can only observe an increase or a decrease between “young” “old” animals, failing capture any dynamic, non-linear that occur throughout the aging process. We used RNA sequencing male head tissue 15 through lifespan of inbred Drosophila melanogaster strain. detected >6,000 significant, age-related...

We develop and implement a strategy to map QTL in two synthetic populations of Drosophila melanogaster each initiated with eight inbred founder strains. These recombinant allow simultaneous estimates location, effect, frequency. Five X-linked influencing bristle number were resolved intervals approximately 1.3 cM. confirm previous observations distal 4A at the tip chromosome identify novel 7F-8C, an interval that does not include any classic candidate genes. If X are biallelic they appear be...

The herpes simplex virus 1 (HSV-1) strain McKrae is highly virulent compared to other wild-type strains of HSV-1. To help us better understand the genetic determinants that lead differences in pathogenicity and HSV-1 strains, we sequenced its genome. Comparing sequence McKrae's genome 17 revealed genomes differ by at least 752 single nucleotide polymorphisms (SNPs) 86 insertion/deletion events (indels). Although majority these reside noncoding regions, 241 SNPs 10 indels alter protein-coding...

In the process of generating herpes simplex virus 1 (HSV-1) mutations in viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a mutant, termed KOS-NA, that was severely impaired for acute replication eyes and trigeminal ganglia (TG) mice, defective establishing latent infection, reactivated poorly from explanted TG. To identify secondary mutation(s) responsible phenotypes this sequenced KOS-NA genome noted it contained two nonsynonymous UL39, which encodes large subunit...

Considerable natural variation for lifespan exists within human and animal populations. Genetically dissecting this can elucidate the pathways genes involved in aging, help uncover genetic mechanisms underlying risk age-related diseases. Studying aging model systems is attractive due to their relatively short lifespan, ability carry out programmed crosses under environmentally-controlled conditions. Here we investigate architecture of using Drosophila Synthetic Population Resource (DSPR), a...

Abstract The ability to survive periods without food is an important component of individual fitness, and genetic dissection can provide insight into the mechanisms evolution starvation resistance. Everman et al. use several genome-wide... We leverage two complementary Drosophila melanogaster mapping panels genetically dissect resistance—an fitness trait. Using >1600 genotypes from multiparental Synthetic Population Resource (DSPR), we map numerous stress QTL that collectively explain...

Abstract The observation that male genitalia diverge more rapidly than other morphological traits during evolution is taxonomically widespread and likely due to some form of sexual selection. One way elucidate the evolutionary forces acting on these detail genetic architecture variation both within between species, a program research considerably tractable in model system. Drosophila melanogaster its sibling D. simulans, mauritiana, sechellia, are morphologically distinguishable only by...

The severity of the toxic side effects chemotherapy varies among patients, and much this variation is likely genetically based. Here, we use model system Drosophila melanogaster to dissect toxicity methotrexate (MTX), a drug used primarily treat childhood acute lymphoblastic leukemia rheumatoid arthritis. We Synthetic Population Resource, panel recombinant inbred lines derived from multiparent advanced intercross, quantify MTX as reduction in female fecundity. identify three quantitative...

Abstract Populations maintain considerable segregating variation in the response to toxic, xenobiotic compounds. To identify variants associated with resistance boric acid, a commonly-used household insecticide poorly understood mechanism of action, we assayed thousands individuals from hundreds strains. Using Drosophila Synthetic Population Resource (DSPR), multi-parental population (MPP) inbred genotypes, mapped six QTL short genomic regions containing few protein-coding genes (3–188),...

Introduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and shape the evolution of species. The persistent ubiquitous nature heavy pollution provides an opportunity to characterize genetic mechanisms that contribute resistance in natural populations. Methods: We examined variation copper, a common contaminant, using wild collections model organism Drosophila melanogaster . Flies were collected from multiple sites varied copper contamination risk....

Abstract The Enhancer of split complex [E(spl)-C] in Drosophila encompasses a variety functional elements controlling bristle patterning and on the basis prior work is strong candidate for harboring alleles having subtle effects number variation. Here we extend earlier studies identifying associations between phenotypes polymorphisms segregating among inbred laboratory lines test influence E(spl)-C variation natural cohort. We describe results from an association mapping study using 203...

Abstract Identifying the sequence polymorphisms underlying complex trait variation is a key goal of genetics research, since knowing precise causative molecular events allows insight into pathways governing variation. Genetic analysis traits in model systems regularly starts by constructing QTL maps, but generally fails to identify polymorphisms. Previously we mapped series contributing resistance nicotine Drosophila melanogaster multiparental mapping resource and here use battery functional...