A5037829890- Fibromyalgia and Chronic Fatigue Syndrome Research
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Neuroendocrine regulation and behavior
- Birth, Development, and Health
- Functional Brain Connectivity Studies
- Genomics and Phylogenetic Studies
- Climate Change and Health Impacts
- Diet and metabolism studies
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Epigenetics and DNA Methylation
- Children's Physical and Motor Development
- Genetics and Neurodevelopmental Disorders
- Stress Responses and Cortisol
- Genetic Syndromes and Imprinting
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Animal Behavior and Reproduction
- RNA Research and Splicing
- Cognitive Abilities and Testing
- Spaceflight effects on biology
- Mitochondrial Function and Pathology
- Gene expression and cancer classification
University of Tennessee Health Science Center
2017-2025
Center for Cancer Research
2024
Institut thématique Génétique, génomique et bioinformatique
2024
Ducks Unlimited
2024
University of Toronto
2017-2018
University of Manchester
2013-2017
Eastern Illinois University
2011
Abstract Pangenome graphs can represent all variation between multiple reference genomes, but current approaches to build them exclude complex sequences or are based upon a single reference. In response, we developed the PanGenome Graph Builder (PGGB), pipeline for constructing pangenome without bias exclusion. PGGB uses all-to-all alignments graph in which identify variation, measure conservation, detect recombination events, and infer phylogenetic relationships.
We have developed workflows to align 3D magnetic resonance histology (MRH) of the mouse brain with light sheet microscopy (LSM) and delineations same specimen. start MRH in skull gradient echo diffusion tensor imaging (DTI) at 15 μm isotropic resolution which is ~ 1,000 times higher than that most preclinical MRI. Connectomes are generated superresolution tract density images ~5 μm. Brains cleared, stained for selected proteins, imaged by LSM 1.8 μm/pixel. data registered into reference...
Hundreds of inbred mouse strains and intercross populations have been used to characterize the function genetic variants that contribute disease. Thousands disease-relevant traits characterized in mice made publicly available. New including consomics, collaborative cross, expanded BXD, wild-derived add existing complex disease models, mapping populations, sensitized backgrounds for engineered mutations. The genome sequences strains, along with dense genotypes from others, enable integrated...
Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and neuroimmune neuroinflammatory components. An estimated 25-32% of the over 900,000 veterans 1991 fulfil requirements a GWI diagnosis. It has been hypothesised that high physical psychological stress combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading priming system. A number studies linked levels...
Genome-wide association studies have demonstrated significant links between human brain structure and common DNA variants. Similar with rodents been challenging because of smaller volumes. Using high field MRI (9.4 T) compressed sensing, we achieved microscopic resolution sufficiently throughput for rodent population studies. We generated whole structural diffusion connectomes four diverse isogenic lines mice (C57BL/6J, DBA/2J, CAST/EiJ, BTBR) at spatial 20,000 times higher than connectomes....
Variation in hippocampal volume has been linked to significant differences memory, behavior, and cognition among individuals. To identify genetic variants underlying such associated disease phenotypes, multinational consortia as ENIGMA have used large magnetic resonance imaging (MRI) data sets human GWAS studies. In addition, mapping studies mouse model systems identified for brain structure variation with great power. A key challenge is understand how genetically based lead the propensity...
Abstract The challenge of precision medicine is to model complex interactions among DNA variants, sets phenotypes, and environmental factors confounders. We have expanded the BXD family, creating a powerful extensible test bed for experimental an ideal cohort study gene-by-environmental interactions. These segregate over 6 million with mean minor allele frequency close 0.5. increased family two-fold 150 inbred strains, all derived from C57BL/6J DBA/2J. also generated updated comprehensive...
DNA methylation (DNAm) is shaped by genetic and environmental factors modulated aging. Here, we examine interrelations between epigenetic aging, body weight (BW), life span in 12 isogenic strains from the BXD family of mice that exhibit over twofold variation longevity. Genome-wide DNAm was assayed 70 liver specimens predominantly female cases, 6-25 months old, were maintained on normal chow or high-fat diet (HFD). We defined subsets CpG regions associated with age, BW at young adulthood,...
Conflict over parental investment between parent and offspring is predicted to lead selection on genes expressed in for traits influencing maternal investment, parentally affecting behaviour. However, the specific genetic variants that indirectly modify or behaviour remain largely unknown. Using a cross-fostered population of mice, we map genetically uniform mothers as function variation identify loci chromosomes 5 7 Conversely, found among influences development, independent genotype....
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning ME/CFS patients as well specific genetic polymorphisms and alterations the DNA methylome lymphocytes. However, potential interactions between methylation background relation have not been examined. In this study we explored association by characterizing epigenetic (~480 thousand CpG loci) (~4.3 million SNPs) variation cohorts...
Alzheimer's disease (AD) affects brain regions with remarkable heterogeneity, but the precise impact of this on hundreds small cortical, subcortical, and brainstem remains poorly defined. Here, as a prelude to testing preclinical models prevent AD, we systematically quantified effects human AD mutations in APP PSEN1 231 comprehensively evaluated changes volume unprecedented resolution genetically diverse mice function sex genetic background. We studied 34 5XFAD F1 hybrids 23 sibling controls...
ABSTRACT The fundamental skills for motor coordination and control emerge through development. Neurodevelopmental disorders such as developmental disorder (DCD) lead to impaired acquisition of skills. This study investigated behaviors that reflect the core symptoms human DCD use BXD recombinant inbred strains mice are known have divergent phenotypes in many behavioral traits, including activity. We sought correlate behavior basic tasks with genotypes these reference populations using...
The dynamics of lifespan are shaped by DNA variants that exert effects at different ages. We have mapped genetic loci modulate age-specific mortality using a new actuarial method. started with 6,438 pubescent mice and ended survivorship 559 lived to least 1100 days age. Twenty-nine Vita dynamically strong age-delimited after correction for multiple tests. Fourteen relatively steady but genotype-dependent on from pubescence old age candidate aging rate modulators. Other act most forcefully...
Infant vocalizations are one of the most fundament and innate forms behavior throughout avian mammalian orders. They have a critical role in motivating parental care through this contribute significantly to fitness reproductive success. Dysregulation these has been reported predict risk central nervous system pathologies such as hypoxia, meningitis or autism spectrum disorder. Here we used expanded BXD family mice, diallel cross between DBA/2J C57BL/6J strains, begin process genetically...
Abstract The BXD recombinant inbred (RI) mouse strains are the largest and most deeply phenotyped panel of vertebrate organisms. RIs allow phenotyping isogenic individuals across virtually any environment or treatment. We performed whole genome sequencing generated a compendium SNPs, indels, short tandem repeats, structural variants in these used them to analyze phenomic data accumulated over past 50 years. show that BXDs segregate >6 million with high minor allele which dervied from...
Bipolar disorder (BD) is a significant neuropsychiatric with lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS) have been carried out. While many small effect associated identified few yet confirmed, partly because the low power GWAS due to multiple comparisons being made. Complementary mapping using murine models for behavioral traits linked BD, often high power, but these regions contain too genes clear identification candidate...
Abstract Genetic differences among mammalian hosts and strains of Mycobacterium tuberculosis (Mtb) are well-established determinants (TB) patient outcomes. The advent recombinant inbred mouse panels next-generation transposon mutagenesis sequencing approaches has enabled dissection complex host–pathogen interactions. To identify host pathogen genetic Mtb pathogenesis, we infected members the highly diverse BXD family with a comprehensive library mutants (TnSeq). Members segregate for...
Acute lung injury (ALI) is an important cause of morbidity and mortality after viral infections, including influenza A virus H1N1, SARS-CoV, MERS-CoV, SARS-CoV-2. The angiotensin I converting enzyme 2 (ACE2) a key host membrane-bound protein that modulates ALI induced by infection, pulmonary acid aspiration, sepsis. However, the contributions ACE2 sequence variants to individual differences in disease risk severity infection are not understood. In this study, we quantified H1N1...
Family members show behavioural strategies predicted to maximize individual fitness. These behaviours depend directly on genes expressed in focal individuals but also indirectly other family members. However, how sibling and parental are modified by members, what degree, remains unclear. To answer this question, we have used a split litter design an experimental population of genetically variable mouse families, identified loci that affected maternal behaviour simultaneously. map genomic...