A5082241434- Genetic Mapping and Diversity in Plants and Animals
- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- Genetic and phenotypic traits in livestock
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Animal Virus Infections Studies
- Tuberculosis Research and Epidemiology
- RNA Research and Splicing
- Mycobacterium research and diagnosis
- Immune Cell Function and Interaction
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Molecular Biology Techniques and Applications
- COVID-19 Clinical Research Studies
- Computational Drug Discovery Methods
- Epigenetics and DNA Methylation
- Food Allergy and Anaphylaxis Research
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Viral gastroenteritis research and epidemiology
- RNA regulation and disease
- Allergic Rhinitis and Sensitization
- Genetics and Neurodevelopmental Disorders
University of North Carolina at Chapel Hill
2019-2024
University of North Carolina Health Care
2023
University of Utah
2022
Boston University
2022
Pediatrics and Genetics
2022
Stanford University
2022
Duke Medical Center
2009-2015
Duke University
2010-2012
Duke University Hospital
2009-2012
The outcome of an encounter with Mycobacterium tuberculosis ( Mtb ) depends on the pathogen’s ability to adapt variable immune pressures exerted by host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate heterogeneity disease. We leveraged genetically diverse Collaborative Cross (CC) mouse panel in conjunction a library mutants create resource for associating bacterial genetic requirements host genetics and immunity....
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and ability precisely manipulate genome. Despite importance genetics quality control (QC) not standardized, lack cost-effective, informative, robust platforms. Genotyping arrays are standard tools research remain an attractive alternative even era high-throughput whole-genome sequencing. Here, we describe content performance a new iteration...
α-Synuclein ( SNCA) gene has been implicated in the development of rare forms familial Parkinson disease (PD). Recently, it was shown that an increase SNCA copy numbers leads to elevated levels wild-type SNCA- mRNA and protein is sufficient cause early-onset, PD. A critical question concerning molecular pathogenesis PD what contributory role, if any, played by sporadic The expansion -Rep1, upstream, polymorphic microsatellite gene, associated with risk for However, whether -Rep1 causal...
Abstract Background We investigated the genomic region spanning Translocase of Outer Mitochondrial Membrane 40‐kD ( TOMM40 ) and Apolipoprotein E APOE genes, that has been associated with risk age onset late‐onset Alzheimer's disease (LOAD) to determine whether a highly polymorphic, intronic poly‐T within this (rs10524523; hereafter, 523) affects expression genes. Alleles locus are classified as S, short; L, long; VL, very long based on number T residues. Methods evaluated differences in...
Genetic variability across the SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinson's disease (PD). Accumulated evidence emphasizes importance of dosage and expression levels in PD pathogenesis. However whether genetic gene modulates risk develop via regulation remained elusive. We studied effect risk-associated variants at 5' 3'regions on SNCA-mRNA vivo 228 human brain samples from three structures differentially vulnerable pathology (substantia-nigra,...
Two key features of recombinant inbred panels are well-characterized genomes and reproducibility. Here we report on the sequenced six additional Collaborative Cross (CC) strains inbreeding progress 72 CC strains. We have previously reported sequences 69 that were publicly available, bringing total with whole genome sequence up to 75. The sequencing these updates efforts toward undertaken by UNC Systems Genetics Core. timing reflects our competing mandates release public as many possible...
Coronavirus (CoV) cause considerable morbidity and mortality in humans other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) 2003, Middle East (MERS-CoV) 2012, SARS-CoV-2 2019. Although poorly characterized, natural genetic variation human mammals modulate virus pathogenesis, reflected spectrum clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple epidemic zoonotic Sarbecoviruses, coupled with murine Collaborative Cross...
We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset Alzheimer's disease and cognitive performance elderly. Three allele groups were defined for rs10524523, hereafter '523', based on number 'T'-residues: 'Short' (S, T≤19), 'Long' (L, 20≤T≤29) 'Very Long' (VL, T≥30). Homopolymers, particularly long homopolymers like are difficult to genotype because 'slippage' occurs during...
A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset.To explore the effects polyT tract (rs10524523, referred as '523') on cognitive performance in cognitively healthy elderly individuals.One hundred eighty-one participants were recruited from local independent-living retirement communities. Informed consent obtained, completed demographic questionnaires, a conventional paper-and-pencil neuropsychological battery,...
Background & Aims: Human genetic variation is thought to guide the outcome of HCV infection, but model systems within which dissect these host mechanisms are limited. Norway rat hepacivirus, closely related HCV, causes chronic liver infection in rats acute self-limiting hepatitis typical strains laboratory mice, resolves 2 weeks. The Collaborative Cross (CC) a robust mouse genetics resource comprised panel recombinant inbred strains, complexity human genome and provide system understand...
Abstract Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these are protective against homologous coronavirus infection, emergence of novel variants and presence large zoonotic reservoirs harboring heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises risk adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female...
Abstract Introduction We recently showed that tagging single‐nucleotide polymorphisms across the SNCA locus were significantly associated with increased risk for Lewy body (LB) pathology in Alzheimer's disease (AD) cases. However, actual genetic variant(s) underlie observed associations remain elusive. Methods used a bioinformatics algorithm to catalog structural variants region of intron 4, followed by phased sequencing. performed association analysis autopsy series LB variant (LBV/AD)...
Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success, as mutations can dramatically alter efficacy addiction liability. We found robust, sex-dependent BALB/c substrain differences in oxycodone behaviors whole brain concentration metabolites. BALB/cJ females showed robust state-dependent reward learning measured via conditioned place preference when compared with closely related BALB/cByJ substrain. Accordingly, also a increase inactive...
Coronaviruses have caused three severe epidemics since the start of 21
Abstract The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well annotated genome, wealth of genetic resources and ability precisely manipulate genome. Despite importance genetics quality control (QC) not standardized, lack cost effective, informative robust platforms. Genotyping arrays are standard tools research remain an attractive alternative even era high-throughput whole genome sequencing. Here we describe content performance a new...
Abstract The outcome of an encounter with Mycobacterium tuberculosis depends on the pathogen’s ability to adapt variable immune pressures exerted by host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate heterogeneity disease. We leveraged genetically diverse Collaborative Cross (CC) mouse panel in conjunction a library Mtb mutants associate bacterial genetic requirements host genetics and immunity. report that CC...
Abstract Background & Aims Human genetic variation is thought to guide the outcome of hepatitis C virus (HCV) infection but model systems within which dissect these host mechanisms are limited. Norway rat hepacivirus (NrHV), closely related HCV, causes chronic liver in rats acute self-limiting typical strains laboratory mice, resolves two weeks. The Collaborative Cross (CC) a robust mouse genetics resource comprised panel recombinant inbred strains, complexity human genome and provide...
Summary Variation in immune homeostasis, system stability, organ systems such as the lungs is likely to shape host response infection at these exposed tissues. We evaluated homeostasis cell populations of Collaborative Cross (CC) mouse genetic reference population. found vast heritable variation leukocyte with frequency many types showing distinct patterns relative classic inbred strains C57BL/6J and BALB/cJ. identified 28 quantitative trait loci (QTL) associated baseline lung populations,...
Variation in immune homeostasis, the state which system is maintained absence of stimulation, highly variable across populations. This variation attributed to both genetic and environmental factors. However, identity function specific regulators have been difficult identify humans. We evaluated homeostatic antibody levels serum Collaborative Cross (CC) mouse reference population. found heritable all isotypes subtypes measured. identified 4 quantitative trait loci (QTL) associated with 3 IgG...
RNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary of novel variants relative well-studied genotypes epidemic viruses. Competition assays are an effective rigorous system which assess genotypes. However, it challenging cheaply distinguish quantify differences between very similar Here, we describe a protocol using reverse...