A5018305231- Genetic Mapping and Diversity in Plants and Animals
- Genetic and phenotypic traits in livestock
- Chromosomal and Genetic Variations
- interferon and immune responses
- Adipose Tissue and Metabolism
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- Genetics and Physical Performance
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Genetic diversity and population structure
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Evolution and Genetic Dynamics
- Animal Virus Infections Studies
- Influenza Virus Research Studies
- Erythrocyte Function and Pathophysiology
- Genetic Syndromes and Imprinting
- Genetic Associations and Epidemiology
- Lipid Membrane Structure and Behavior
- Cancer-related molecular mechanisms research
- Genomics and Rare Diseases
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
University of North Carolina at Chapel Hill
2016-2025
UNC Lineberger Comprehensive Cancer Center
2016-2025
University of North Carolina at Charlotte
2024
University of North Carolina Health Care
2014-2023
University of North Carolina System
2023
Pediatrics and Genetics
2010-2022
Public Health Department
2020
Segeberger Kliniken
2005-2018
University of Concepción
2000-2016
Communities In Schools of Orange County
2014
Ovarian clear-cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a mutant mouse model OCCC. We find that inactivation not sufficient for tumour formation, but requires concurrent activation the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, mice develop highly penetrant tumours OCCC-like histopathology, culminating in haemorrhagic ascites and median survival period 7.5 weeks. Therapeutic treatment pan-PI3K...
Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice the Collaborative Cross panel recombinant inbred exhibit distinct disease phenotypes after mouse-adapted infection. Phenotypes range complete resistance severe fever characterized by prolonged times 100% mortality....
Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the integrity laboratory stocks. We have developed third generation Mouse Universal Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array house mouse (Mus musculus). The bulk content GigaMUGA is optimized mapping in Collaborative Cross Diversity Outbred populations, substrain-level identification mice. In addition to 141,090 single nucleotide polymorphism probes,...
Abstract The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because their long-term genetic stability, which enhances reproducibility and integration data collected across time conditions. Characterization genomes can be community effort, reducing the burden on individual users. Here we present CC using two complementary approaches as resource to improve power interpretation...
Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms confounding environmental factors have made it difficult identify polymorphic genes that contribute differential in human populations. Therefore, control for these variables a system models the levels genetic diversity found outbred populations such as humans, we used incipient lines highly genetically diverse Collaborative...
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....
Mouse genetic resources include inbred strains, recombinant lines, chromosome substitution heterogeneous stocks, and the Collaborative Cross (CC). These were generated through various breeding designs that potentially produce different architectures, including level of diversity represented, spatial distribution variation, allele frequencies within resource. By combining sequencing data for 16 strains recorded history related architecture variation in mouse was determined. The most commonly...
New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range phenotypes relative classical models SARS-CoV infection including lung pathology, weight loss viral titer. Genetic mapping revealed several loci contributing differential responses, an 8.5Mb locus associated with vascular...
The Collaborative Cross (CC) is a genetic reference panel of recombinant inbred lines mice, designed for the dissection complex traits and gene networks. Each line independently descended from eight genetically diverse founder strains such that genomes CC lines, once fully inbred, are fine-grained homozygous mosaics haplotypes. We present an analysis 120 cohort bred at Tel Aviv University in collaboration with Oxford, which time this study were between sixth 12th generations inbreeding...
The Collaborative Cross (CC) is a panel of recombinant inbred lines derived from eight genetically diverse laboratory strains. Recently, the genetic architecture CC population was reported based on genotype single male per line, and other publications incompletely mice that have been used to map variety traits. three breeding sites, in US, Israel, Australia, are actively collaborating accelerate inbreeding process through marker-assisted expedite community access deemed reached defined...
The outcome of respiratory virus infection is determined by a complex interplay viral and host factors. Some potentially important factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred regulatory lncRNAs in response to influenza A severe acute syndrome coronavirus (SARS-CoV) based on their similarity expression with genes known function. We performed total RNA-Seq viral-infected lungs from eight...
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...
Abstract Hematological parameters, including red and white blood cell counts hemoglobin concentration, are widely used clinical indicators of health disease. These traits tightly regulated in healthy individuals under genetic control. Mutations key genes that affect hematological parameters have important phenotypic consequences, multiple variants susceptibility to malarial However, most variation is continuous presumably influenced by loci with small effects. We a newly developed mouse...
Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported multiple crosses, including the Collaborative Cross (CC). Among eight CC founder inbred strains, we found that Chr was exclusive to females were heterozygous for WSB/EiJ allele within a 9.3 Mb region (Chr 76.9 - 86.2 Mb). A copy number gain of 127 kb-long DNA...
Host genetic variation is known to contribute differential pathogenesis following infection. Mouse models allow direct assessment of host factors responsible for susceptibility Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an early stage lines from the Collaborative Cross mouse multi-parent population, we identified two showing highly divergent susceptibilities SARS-CoV: resistant CC003/Unc and susceptible CC053/Unc. We generated 264 F2 mice between these strains,...
Outbreaks of influenza occur on a yearly basis, causing wide range symptoms across the human population. Although evidence exists that host response to infection is influenced by genetic differences in host, this has not been studied system with diversity mirroring Here we used mice from 44 influenza-infected pre-Collaborative Cross lines determined have extreme phenotypes regard A virus infection. Global transcriptome profiling identified 2671 transcripts were significantly differentially...
The Collaborative Cross (CC) is an emerging panel of recombinant inbred (RI) mouse strains. Each strain genetically distinct but all descended from the same eight founders. In 66 strains incipient lines CC (pre-CC), as well 8 founders and some their F1 offspring, we examined subsets lymphocytes antigen-presenting cells. We found significant variation among founders, with even greater diversity in pre-CC. Genome-wide association using inferred haplotypes detected highly loci controlling...
Since the publication of first comprehensive linkage map for laboratory mouse, architecture recombination as a basic biological process has become amenable to investigation in mammalian model organisms. Here we take advantage high-density genotyping and unique pedigree structure incipient Collaborative Cross investigate roles sex genetic background recombination. Our results confirm observation that length is longer when measured through female meiosis than male meiosis, but find this...
Abstract Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution mapping through accumulation of recombination events over many generations. Breeding designs that large effective population size with randomized assignment breeders at each generation can minimize impact selection, inbreeding, drift on allele frequencies. Small deviations expected frequencies will have little effect power...
Abstract The goal of the Collaborative Cross (CC) project was to generate and distribute over 1000 independent mouse recombinant inbred strains derived from eight founders. With inbreeding nearly complete, we estimated extinction rate among CC lines at a remarkable 95%, which is substantially higher than in derivation other populations. Here, report genome-wide allele frequencies 347 extinct lines. Contrary expectations, autosomes had equal allelic contributions founders, but chromosome X...