A5052323669- Genetic Mapping and Diversity in Plants and Animals
- Genetic diversity and population structure
- Malaria Research and Control
- Chromosomal and Genetic Variations
- Genetic and phenotypic traits in livestock
- Animal Genetics and Reproduction
- Evolution and Genetic Dynamics
- Gut microbiota and health
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Molecular Biology Techniques and Applications
- Tryptophan and brain disorders
- Mosquito-borne diseases and control
- Genomics and Chromatin Dynamics
- Diversity and Career in Medicine
- Atherosclerosis and Cardiovascular Diseases
- Genetic factors in colorectal cancer
- Bat Biology and Ecology Studies
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Genetic Syndromes and Imprinting
- Diet and metabolism studies
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
University of North Carolina at Chapel Hill
2014-2024
Duke University Hospital
2020-2023
Duke University
2023
UNC Lineberger Comprehensive Cancer Center
2014-2022
University of Missouri–Kansas City
2022
Pediatrics and Genetics
2016-2017
Jackson Laboratory
2017
Idaho State University
2009
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...
The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain human patients. We investigated the role of gut microbiota this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that bacteria are necessary and sufficient for caused by oral delivery olanzapine. Second, surveyed fecal before, during, after treatment found potentiated shift towards an “obesogenic” bacterial profile....
Abstract The Democratic Republic of the Congo (DRC) harbors 11% global malaria cases, yet little is known about spatial and genetic structure parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative sample from DRC samples surrounding countries, using molecular inversion probes - high-throughput genotyping tool. identify an east-west divide haplotypes to confer resistance chloroquine sulfadoxine-pyrimethamine. Furthermore,...
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...
Inflammatory bowel disease (IBD) is an immune-mediated condition driven by improper responses to intestinal microflora in the context of environmental and genetic background. GWAS humans have identified many loci associated with IBD, but animal models are valuable for dissecting underlying molecular mechanisms, characterizing contributions developing treatments. Mouse rely on interventions such as chemical treatment or introduction infectious agent induce disease. Here, we describe a new...
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,...
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...
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 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...
Abstract Meiotic recombination ensures the faithful segregation of chromosomes and influences patterns genetic diversity. Morgan et al. used genotype data.. is an essential feature sexual reproduction that redistributes variants in populations. Multiparent populations such as Diversity Outbred (DO) mouse stock accumulate large numbers crossover (CO) events between founder haplotypes, thus present a unique opportunity to study role variation shaping landscape. We obtained high-density data...
A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter pattern distribution allelic diversity in a population. Population-level sequencing data have enabled discoveries sweeps associated with genes involved recent adaptations many species. In contrast, much debate but little evidence addresses whether “selfish” are capable fixation—thereby leaving signatures identical classical sweeps—despite...
Over the 180 My since their origin, sex chromosomes of mammals have evolved a gene repertoire highly specialized for function in male germline. The mouse Y chromosome is unique among mammalian characterized to date that it large, gene-rich and euchromatic. Yet, little known about its diversity natural populations. Here, we take advantage published whole-genome sequencing data survey sequence copy number sex-linked genes three subspecies house mice. Copy on repetitive long arm both variable,...
Tanzania's Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for elimination. Despite consistent implementation of effective tools since 2002, elimination not been achieved. Importation parasites from outside thought to be an important cause malaria's persistence, but this paradigm studied using modern genetic tools. Whole-genome sequencing (WGS) was used investigate impact importation, employing population analyses Plasmodium falciparum...
Abstract Genotyping microarrays are an important and widely-used tool in genetics. I present argyle, R package for analysis of genotyping array data tailored to Illumina arrays. The goal the argyle is provide simple, expressive tools nonexpert users perform quality checks exploratory analyses data. To these ends, consists a suite quality-control functions, normalization procedures, utilities visually statistically summarizing such Format-conversion allow interoperability with popular...
Abstract The classical definition posits hybrid sterility as a phenomenon when two parental taxa each of which is fertile produce that sterile. first gene in vertebrates, Prdm9, coding for histone methyltransferase, was identified crosses between laboratory mouse strains derived from Mus mus musculus and M. m. domesticus subspecies. unique function PRDM9 protein the initiation meiotic recombination led to discovery basic molecular mechanism crosses. However, role this component reproductive...
Reports of P. vivax infections among Duffy-negative hosts have accumulated throughout sub-Saharan Africa. Despite this growing body evidence, no nationally representative epidemiological surveys in Africa been performed. To overcome gap knowledge, we screened over 17,000 adults the Democratic Republic Congo (DRC) for using samples from 2013-2014 Demographic Health Survey. Overall, found a 2.97% (95% CI: 2.28%, 3.65%) prevalence across DRC. Infections were associated with few risk-factors and...
Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa with dimorphic sex chromosomes, between them in the heterogametic is limited to a narrow interval residual sequence homology known as pseudoautosomal region (PAR). Failure form obligate crossover PAR associated male infertility house mice (Mus musculus) humans. Yet despite this apparent functional constraint, boundary organization highly variable mammals, even subspecies mice. Here, we...
Gene duplication and loss are major sources of genetic polymorphism in populations, important forces shaping the evolution genome content organization. We have reconstructed origin history a 127-kbp segmental duplication, R2d, house mouse (Mus musculus). R2d contains single protein-coding gene, Cwc22 De novo assembly both ancestral (R2d1) derived (R2d2) copies reveals that they been subject to nonallelic gene conversion events spanning tens kilobases. R2d2 is also hotspot for structural...
Abstract Background Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine in absence of amplified plasmepsin II (pfpm2). In this study, we estimated prevalence co-circulating P. isolates collected northern Cambodia from 2009 to 2017. Methods The sequence pfcrt was determined for 410 using PacBio amplicon sequencing or whole genome sequencing. Quantitative polymerase chain reaction used estimate pfpm2 and pfmdr1 copy number....