scholarly journals Variation in the response to malaria in Diversity Outbred mice

2021 ◽  
Author(s):  
Avni S Gupta ◽  
Victoria Chevee ◽  
Adam S. Kirosingh ◽  
Nicole M Davis ◽  
David S Schneider
Keyword(s):  
Host Response ◽  
Statistical Significance ◽  
Plasmodium Chabaudi ◽  
Genetic Loci ◽  
Binary Traits ◽  
Diversity Outbred ◽  
Outbred Mice

We infected Diversity Outbred mice with Plasmodium chabaudi to better understand how the host response to infection can vary and to try to identify genetic loci responsible for this variation. We identified two loci correlating with binary traits: one on chromosome two was linked to undetectable parasite loads and another on chromosome ten which was linked to death. Though we tested many variable traits, none of those reached statistical significance using the 489 mice we tested.

scholarly journals Correction to: Quantitative trait mapping in Diversity Outbred mice identifies two genomic regions associated with heart size

2018 ◽  
Vol 30 (1-2) ◽  
pp. 42-42
Author(s):  
John R. Shorter ◽  
Wei Huang ◽  
Ju Youn Beak ◽  
Kunjie Hua ◽  
Daniel M. Gatti ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Trait Mapping ◽  
Quantitative Trait Mapping ◽  
Diversity Outbred ◽  
Heart Size ◽  
Outbred Mice ◽  
Genomic Regions

scholarly journals Precise genetic mapping and integrative bioinformatics in Diversity Outbred mice reveals Hydin as a novel pain gene

2014 ◽  
Vol 25 (5-6) ◽  
pp. 211-222 ◽  
Author(s):  
Jill M. Recla ◽  
Raymond F. Robledo ◽  
Daniel M. Gatti ◽  
Carol J. Bult ◽  
Gary A. Churchill ◽  
...  
Keyword(s):  
Genetic Mapping ◽  
Diversity Outbred ◽  
Outbred Mice

scholarly journals Genetic mapping in Diversity Outbred mice identifies a Trpa1 variant influencing late-phase formalin response

Pain ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1740-1753 ◽  
Author(s):  
Jill M. Recla ◽  
Jason A. Bubier ◽  
Daniel M. Gatti ◽  
Jennifer L. Ryan ◽  
Katie H. Long ◽  
...  
Keyword(s):  
Genetic Mapping ◽  
Late Phase ◽  
Diversity Outbred ◽  
Outbred Mice

scholarly journals Age-associated changes in hippocampal-dependent cognition in Diversity Outbred mice

Hippocampus ◽  
2014 ◽  
Vol 24 (11) ◽  
pp. 1300-1307 ◽  
Author(s):  
Ming Teng Koh ◽  
Amy M. Spiegel ◽  
Michela Gallagher
Keyword(s):  
Diversity Outbred ◽  
Outbred Mice

scholarly journals Quantitative trait mapping in Diversity Outbred mice identifies two genomic regions associated with heart size

2017 ◽  
Vol 29 (1-2) ◽  
pp. 80-89 ◽  
Author(s):  
John R. Shorter ◽  
Wei Huang ◽  
Ju Youn Beak ◽  
Kunjie Hua ◽  
Daniel M. Gatti ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Trait Mapping ◽  
Quantitative Trait Mapping ◽  
Diversity Outbred ◽  
Heart Size ◽  
Outbred Mice ◽  
Genomic Regions

scholarly journals Idiosyncratic Drug‐Induced Liver Injury Potential of Zileuton is Detected in Diversity Outbred Mice

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Alison Harrill ◽  
Lascelles Lyn‐cook ◽  
Daniel Gatti ◽  
Shaoke Luo ◽  
Gary Churchill
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Diversity Outbred ◽  
Outbred Mice ◽  
Injury Potential

scholarly journals The Effects of Sex and Diet on Physiology and Liver Gene Expression in Diversity Outbred Mice

2017 ◽  
Author(s):  
Daniel M. Gatti ◽  
Petr Simecek ◽  
Lisa Somes ◽  
Clifton T. Jeffrey ◽  
Matthew J. Vincent ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Transcript Abundance ◽  
Physiological Traits ◽  
Chow Diet ◽  
Late Time ◽  
High Fat ◽  
Cholesterol Levels ◽  
Diversity Outbred ◽  
Outbred Mice ◽  
Liver Gene

ABSTRACTInter-individual variation in metabolic health and adiposity is driven by many factors. Diet composition and genetic background and the interactions between these two factors affect adiposity and related traits such as circulating cholesterol levels. In this study, we fed 850 Diversity Outbred mice, half females and half males, with either a standard chow diet or a high fat, high sucrose diet beginning at weaning and aged them to 26 weeks. We measured clinical chemistry and body composition at early and late time points during the study, and liver transcription at euthanasia. Males weighed more than females and mice on a high fat diet generally weighed more than those on chow. Many traits showed sex- or diet-specific changes as well as more complex sex by diet interactions. We mapped both the physiological and molecular traits and found that the genetic architecture of the physiological traits is complex, with many single locus associations potentially being driven by more than one polymorphism. For liver transcription, we find that local polymorphisms affect constitutive and sex-specific transcription, but that the response to diet is not affected by local polymorphisms. We identified two loci for circulating cholesterol levels. We performed mediation analysis by mapping the physiological traits, given liver transcript abundance and propose several genes that may be modifiers of the physiological traits. By including both physiological and molecular traits in our analyses, we have created deeper phenotypic profiles to identify additional significant contributors to complex metabolic outcomes such as polygenic obesity. We make the phenotype, liver transcript and genotype data publicly available as a resource for the research community.

scholarly journals Intermittent fasting and caloric restriction interact with genetics to shape physiological health in mice

2021 ◽  
Author(s):  
Guozhu Zhang ◽  
Andrew Deighan ◽  
Anil Raj ◽  
Laura Robinson ◽  
Hannah J. Donato ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Dietary Intervention ◽  
Early Adulthood ◽  
Genetic Correlations ◽  
Intermittent Fasting ◽  
Cardiac Physiology ◽  
Dietary Interventions ◽  
Diversity Outbred ◽  
Outbred Mice ◽  
One Year

Dietary interventions can dramatically affect physiological health and organismal lifespan. The degree to which organismal health is improved depends upon genotype and the severity of dietary intervention, but neither the effects of these factors, nor their interaction, have been quantified in an outbred population. Moreover, it is not well understood what physiological changes occur shortly after dietary change and how these may affect the health of early adulthood population. In this article, we investigated the effect of six month exposure of either caloric restriction or intermittent fasting on a broad range of physiological traits in 960 one year old Diversity Outbred mice. We found caloric restriction and intermittent fasting affected distinct aspects of physiology and neither the magnitude nor the direction (beneficial or detrimental) of effects were concordant with the severity of the intervention. In addition to the effects of diet, genetic variation significantly affected 31 of 36 traits (heritabilties ranged from 0.04-0.65). We observed significant covariation between many traits that was due to both diet and genetics and quantified these effects with phenotypic and genetic correlations. We genetically mapped 16 diet-independent and 2 diet-dependent significant quantitative trait loci, both of which were associated with cardiac physiology. Collectively, these results demonstrate the degree to which diet and genetics interact to shape the physiological health of early adult-hood mice following six months of dietary intervention.

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