A5039035475- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Genomics and Phylogenetic Studies
- Neurotransmitter Receptor Influence on Behavior
- Genetic Mapping and Diversity in Plants and Animals
- Genetic diversity and population structure
- Plant Disease Resistance and Genetics
- Chromosomal and Genetic Variations
- Neuropeptides and Animal Physiology
- Neuroendocrine regulation and behavior
- Adipose Tissue and Metabolism
- Plant Pathogens and Fungal Diseases
- Radiomics and Machine Learning in Medical Imaging
- Bioenergy crop production and management
- AI in cancer detection
- Genetic and phenotypic traits in livestock
- Anesthesia and Neurotoxicity Research
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- Wheat and Barley Genetics and Pathology
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Nuclear Receptors and Signaling
- Neurobiology and Insect Physiology Research
Commonwealth Scientific and Industrial Research Organisation
2018-2025
Australian National University
2018-2024
Rocky Vista University
2024
BioDelivery Sciences International (United States)
2024
Children's Hospital of Western Ontario
2024
Western University of Health Sciences
2024
Western University
2024
Harvard University
2024
Cleveland Clinic
2024
Rush University Medical Center
2024
A major challenge of biology is understanding the relationship between molecular genetic variation and in quantitative traits, including fitness. This determines our ability to predict phenotypes from genotypes understand how evolutionary forces shape within species. Previous efforts dissect genotype–phenotype map were based on incomplete genotypic information. Here, we describe Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis population genomics...
Comparisons of orthologous genomic DNA sequences can be used to characterize regions that have been subject purifying selection and are enriched for functional elements. We here present the results such an analysis on alignment from 29 mammalian species. The captures ∼3.9 neutral substitutions per site spans ∼1.9 Mbp human genome. identify constrained elements 3 bp over 1 kbp in length, covering ∼5.5% locus. Our estimate total amount nonexonic constraint experienced by this locus is roughly...
The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding the effects naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy identify 4,853,802 single nucleotide polymorphisms (SNPs) 1,296,080 non-SNP variants. Our population genomic analyses show higher deletion than insertion mutation rates stronger purifying selection deletions....
We find that the degree of impairment protein function by missense variants is predictable comparative sequence analysis alone. The applicable range not confined to binary predictions distinguish normal from deleterious variants, but extends continuously mild severe effects. accuracy strongly dependent on variation and highest when diverse orthologs are available. High predictive achieved quantification physicochemical characteristics in each position protein, based observed evolutionary...
Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding synaptic protein SHANK3 in 285 controls 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X R536W) were identified two families, one being found three affected brothers, suggesting germline mosaicism. Zebrafish rat hippocampal neuron assays revealed behavior differentiation defects resulting R1117X mutant. As previously reported autism, occurrence...
Saccharomyces cerevisiae , a well-established model for species as diverse humans and pathogenic fungi, is more recently population quantitative genetics. S. found in multiple environments—one of which the human body—as an opportunistic pathogen. To aid understanding genetics, well its emergence pathogen, we sequenced, de novo assembled, extensively manually edited annotated genomes 93 strains from geographic environmental origins, including many clinical origin strains. These strains, are...
Epistasis—nonlinear genetic interactions between polymorphic loci—is the basis of canalization and speciation, epistatic can be used to infer networks affecting quantitative traits. However, role that epistasis plays in architecture traits is controversial. Here, we compared three Drosophila life history sequenced inbred lines melanogaster Genetic Reference Panel (DGRP) a large outbred, advanced intercross population derived from 40 DGRP (Flyland). We assessed allele frequency changes pools...
In phylogenetic inference, we commonly use models of substitution which assume that sequence evolution is stationary, reversible, and homogeneous (SRH). Although the such often criticized, extent SRH violations their effects on inference tree topologies edge lengths are not well understood. Here, introduce apply maximal matched-pairs tests homogeneity to assess scale impact model 3,572 partitions from 35 published data sets. We show roughly one-quarter all analyzed (23.5%) reject...
A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for initially targeted 1% human genome. Here, we present orthologous generation, alignment, and evolutionary constraint 23 mammalian species all targets. Alignments were generated using four different methods; comparisons these methods reveal large-scale consistency but substantial differences in terms small genomic rearrangements, sensitivity (sequence coverage), specificity (alignment accuracy)....
Predicting organismal phenotypes from genotype data is important for plant and animal breeding, medicine, evolutionary biology. Genomic-based phenotype prediction has been applied single-nucleotide polymorphism (SNP) genotyping platforms, but not using complete genome sequences. Here, we report genomic starvation stress resistance startle response in Drosophila melanogaster, ∼2.5 million SNPs determined by sequencing the Genetic Reference Panel population of inbred lines. We constructed a...
Problems with current hypotheses of catecholamine involvement in antidepressant action are reviewed. The theories examined include those that attribute a key role to increased brain norepinephrine (NE) availability or the desensitization beta adrenergic receptors. Although these consistent great deal relevant laboratory and clinical data there arc an increasing number findings cannot be explained by them. These contradictions on lag time between pharmacological therapeutic effects...
Significance RNA provides a link between variation at the DNA and phenotypic levels. We measured abundances of products protein-coding genes novel transcribed regions in population wild-derived inbred strains Drosophila melanogaster whose genome sequences are also available. exploited this unique resource to characterize genetic basis transcriptome diversity. found high complexity control gene expression, including widespread sexual dimorphism, highly modularized expression patterns with...
Understanding the relationship between genetic and phenotypic variation is one of great outstanding challenges in biology. To meet this challenge, comprehensive genomic maps human as well model organism populations are required. Here, we present a nucleotide resolution catalog single-nucleotide, multi-nucleotide, structural variants 39 Drosophila melanogaster Genetic Reference Panel inbred lines. Using an integrative, local assembly-based approach for variant discovery, identify more than...
Abstract Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It thought that many common variant gene loci of weak effect act additively to predispose diseases, while contribution rare variants remains unclear. Here we describe coding in lupus-risk genes are present most SLE patients and healthy controls. We demonstrate functional consequences low frequency missense interacting proteins BLK BANK1, which alone, or combination, a substantial proportion patients....
Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response changing environments. We assessed variation genome-wide gene expression and four fitness-related an outbred Drosophila melanogaster population under 20 physiological, social, nutritional, chemical, physical environments; we compared phenotypically plastic transcripts genetically variable environment. The environmentally sensitive transcriptome consists two transcript categories, which...