scholarly journals Genetic variability affects the skeletal response to immobilization in founder strains of the diversity outbred mouse population

Bone Reports ◽  
2021 ◽  
pp. 101140
Author(s):  
Michael A. Friedman ◽  
Abdullah Abood ◽  
Bhavya Senwar ◽  
Yue Zhang ◽  
Camilla Reina Maroni ◽  
...  
Keyword(s):  
Genetic Variability ◽  
Mouse Population ◽  
Diversity Outbred ◽  
Outbred Mouse

scholarly journals High-Resolution Genetic Mapping in the Diversity Outbred Mouse Population Identifies Apobec1 as a Candidate Gene for Atherosclerosis

2014 ◽  
Vol 4 (12) ◽  
pp. 2353-2363 ◽  
Author(s):  
Tangi L. Smallwood ◽  
Daniel M. Gatti ◽  
Pamela Quizon ◽  
George M. Weinstock ◽  
Kuo-Chen Jung ◽  
...  
Keyword(s):  
High Resolution ◽  
Genetic Mapping ◽  
Candidate Gene ◽  
Mouse Population ◽  
Diversity Outbred ◽  
Outbred Mouse

scholarly journals Genome-wide association for testis weight in the diversity outbred mouse population

2018 ◽  
Vol 29 (5-6) ◽  
pp. 310-324 ◽  
Author(s):  
Joshua T. Yuan ◽  
Daniel M. Gatti ◽  
Vivek M. Philip ◽  
Steven Kasparek ◽  
Andrew M. Kreuzman ◽  
...  
Keyword(s):  
Genome Wide Association ◽  
Testis Weight ◽  
Mouse Population ◽  
Genome Wide ◽  
Diversity Outbred ◽  
Outbred Mouse

scholarly journals Mapping metabolic traits in the diversity outbred mouse population (818.12)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Brian Bennett ◽  
Tangi Smallwood ◽  
Pamela Quizon ◽  
Daniel Pomp
Keyword(s):  
Mouse Population ◽  
Metabolic Traits ◽  
Diversity Outbred ◽  
Outbred Mouse

scholarly journals High‐precision genetic mapping of behavioral traits in the diversity outbred mouse population

2013 ◽  
Vol 12 (4) ◽  
pp. 424-437 ◽  
Author(s):  
R. W. Logan ◽  
R. F. Robledo ◽  
J. M. Recla ◽  
V. M. Philip ◽  
J. A. Bubier ◽  
...  
Keyword(s):  
Genetic Mapping ◽  
High Precision ◽  
Mouse Population ◽  
Behavioral Traits ◽  
Diversity Outbred ◽  
Outbred Mouse

scholarly journals The diversity outbred mouse population

2012 ◽  
Vol 23 (9-10) ◽  
pp. 713-718 ◽  
Author(s):  
Gary A. Churchill ◽  
Daniel M. Gatti ◽  
Steven C. Munger ◽  
Karen L. Svenson
Keyword(s):  
Mouse Population ◽  
Diversity Outbred ◽  
Outbred Mouse

scholarly journals Facial shape and allometry quantitative trait locus intervals in the Diversity Outbred mouse are enriched for known skeletal and facial development genes

PLoS ONE ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. e0233377
Author(s):  
David C. Katz ◽  
J. David Aponte ◽  
Wei Liu ◽  
Rebecca M. Green ◽  
Jessica M. Mayeux ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Facial Shape ◽  
Diversity Outbred ◽  
Outbred Mouse ◽  
Trait Locus ◽  
Facial Development

scholarly journals Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

2016 ◽  
Vol 6 (12) ◽  
pp. 3893-3902 ◽  
Author(s):  
Elissa J Chesler ◽  
Daniel M Gatti ◽  
Andrew P Morgan ◽  
Marge Strobel ◽  
Laura Trepanier ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Sex Chromosome ◽  
Allelic Variation ◽  
Allele Frequencies ◽  
Transmission Ratio Distortion ◽  
Chromosome 2 ◽  
Effective Population ◽  
Mouse Population ◽  
Diversity Outbred ◽  
The Impact

Abstract Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.

scholarly journals Identification of Genetic Variants Regulating the Abundance of Clinically Relevant Plasma Proteins using the Diversity Outbred Mouse Model

2021 ◽  
Author(s):  
Stéphanie Philtjens ◽  
Dominic J. Acri ◽  
Byungwook Kim ◽  
Hyewon Kim ◽  
Jungsu Kim
Keyword(s):  
Genetic Variants ◽  
Quantitative Trait ◽  
Plasma Proteins ◽  
Systematic Investigation ◽  
Genetic Modifiers ◽  
Gene Encoding ◽  
Mouse Population ◽  
Aryl Hydrocarbon ◽  
Diversity Outbred ◽  
Trait Locus

Abstract Background: Levels of plasma proteins are under control of environmental and genetic factors. To use plasma proteins in biomarker studies, we need to understand how genetic modifiers influence their abundance. Although there has been expression quantitative trait loci (eQTL) studies on a few limited numbers of proteins, the effect of genetic variants on the levels of multiple plasma proteins still warrants more systematic investigation.Results: To identify genetic modifiers that influence the levels of clinically relevant plasma proteins, we performed protein quantitative trait locus (pQTL) mapping on the 92 proteins present in the Olink Mouse Exploratory Panel using the Diversity Outbred (DO) mouse population. We identified 12 significant pQTL that were located in cis and 6 that were in trans. Among them, we discovered that the presence of coding variants in the gene encoding for the Aryl Hydrocarbon Receptor (Ahr) had a significant effect on its abundance in plasma. Most interestingly, we identified variants in the Regulatory Factor X1 (Rfx1) gene that influence the abundance of the IL-17A protein in plasma.Conclusion: Our study reports an innovative pipeline for the identification of genetic modifiers that may be targeted for drug development.

scholarly journals CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice

2021 ◽  
Vol 17 (8) ◽  
pp. e1009773
Author(s):  
Deniz Koyuncu ◽  
Muhammad Khalid Khan Niazi ◽  
Thomas Tavolara ◽  
Claudia Abeijon ◽  
Melanie L. Ginese ◽  
...  
Keyword(s):  
Serum Protein ◽  
Limit Of Detection ◽  
Area Under The Curve ◽  
World Health ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Protein Biomarker ◽  
Mouse Population ◽  
Diagnostic Quality ◽  
Diversity Outbred

More humans have died of tuberculosis (TB) than any other infectious disease and millions still die each year. Experts advocate for blood-based, serum protein biomarkers to help diagnose TB, which afflicts millions of people in high-burden countries. However, the protein biomarker pipeline is small. Here, we used the Diversity Outbred (DO) mouse population to address this gap, identifying five protein biomarker candidates. One protein biomarker, serum CXCL1, met the World Health Organization’s Targeted Product Profile for a triage test to diagnose active TB from latent M.tb infection (LTBI), non-TB lung disease, and normal sera in HIV-negative, adults from South Africa and Vietnam. To find the biomarker candidates, we quantified seven immune cytokines and four inflammatory proteins corresponding to highly expressed genes unique to progressor DO mice. Next, we applied statistical and machine learning methods to the data, i.e., 11 proteins in lungs from 453 infected and 29 non-infected mice. After searching all combinations of five algorithms and 239 protein subsets, validating, and testing the findings on independent data, two combinations accurately diagnosed progressor DO mice: Logistic Regression using MMP8; and Gradient Tree Boosting using a panel of 4: CXCL1, CXCL2, TNF, IL-10. Of those five protein biomarker candidates, two (MMP8 and CXCL1) were crucial for classifying DO mice; were above the limit of detection in most human serum samples; and had not been widely assessed for diagnostic performance in humans before. In patient sera, CXCL1 exceeded the triage diagnostic test criteria (>90% sensitivity; >70% specificity), while MMP8 did not. Using Area Under the Curve analyses, CXCL1 averaged 94.5% sensitivity and 88.8% specificity for active pulmonary TB (ATB) vs LTBI; 90.9% sensitivity and 71.4% specificity for ATB vs non-TB; and 100.0% sensitivity and 98.4% specificity for ATB vs normal sera. Our findings overall show that the DO mouse population can discover diagnostic-quality, serum protein biomarkers of human TB.

scholarly journals Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer

Cell Systems ◽  
2017 ◽  
Vol 4 (1) ◽  
pp. 31-45.e6 ◽  
Author(s):  
Jean M. Winter ◽  
Derek E. Gildea ◽  
Jonathan P. Andreas ◽  
Daniel M. Gatti ◽  
Kendra A. Williams ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Complex Traits ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Mouse Population ◽  
Diversity Outbred ◽  
Mapping Complex Traits
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