Inbred or Outbred? Genetic Diversity in Laboratory Rodent Colonies
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Abstract
Nonmodel rodents are widely used as subjects for both basic and applied biological research, but the genetic diversity of the study individuals is rarely quantified. University-housed colonies tend to be small and subject to founder effects and genetic drift; so they may be highly inbred or show substantial genetic divergence from other colonies, even those derived from the same source. Disregard for the levels of genetic diversity in an animal colony may result in a failure to replicate results if a different colony is used to repeat an experiment, as different colonies may have fixed alternative variants. Here we use high throughput sequencing to demonstrate genetic divergence in three isolated colonies of Mongolian gerbil (Meriones unguiculatus) even though they were all established recently from the same source. We also show that genetic diversity in allegedly “outbred” colonies of nonmodel rodents (gerbils, hamsters, house mice, deer mice, and rats) varies considerably from nearly no segregating diversity to very high levels of polymorphism. We conclude that genetic divergence in isolated colonies may play an important role in the “replication crisis.” In a more positive light, divergent rodent colonies represent an opportunity to leverage genetically distinct individuals in genetic crossing experiments. In sum, awareness of the genetic diversity of an animal colony is paramount as it allows researchers to properly replicate experiments and also to capitalize on other genetically distinct individuals to explore the genetic basis of a trait.
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Rat strains are more commonly used as outbred stocks, so more genetic variability can be expected.
“While the natural genetics of mice and rats follow the same principles, practically, it is important to note that rat stains are more commonly used as outbred stocks where more genetic variability can be expected (Brekke et al., 2018; Wildt et al., 2008).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Brekke et al., 2018
The Abstract (page unavailable) explains that outbred colonies can have standing genetic variation, but also cautions that an “outbred” label may have little bearing on the diversity actually present. The paper does not say that rat stocks are more commonly outbred than mouse stocks; Results Table 2 (page unavailable) instead includes data from 96 inbred rat strains. Thus the general point about potential variability is supported, but the rat-specific comparison and expectation are not. (LLM, conf=0.83)
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Rodent Genetic Models of Ah Receptor Signaling
Wilson, R. H., & Bradfield, C. A. (2021) · Drug Metabolism Reviews · doi:10.1080/03602532.2021.1955916 · Cited by 16 · see citing works
“…in the rat aryl hydrocarbon receptor While the natural genetics of mice and rats follow the same principles, practically, it is important to note that rat stains are more commonly used as outbred stocks where more genetic variability can be expected (Wildt et al. 2008; Brekke et al. 2018).”
Background
- Authors
- Brekke, T. D., Steele, K. A., & Mulley, J. F.
- Affiliations
- Bangor University (GB)
- Corresponding author
- Mulley, John F
- Venue
- G3 Genes|Genomes|Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-02-01
- Volume
- 8
- Issue
- 2
- Pages
- 679-686
- ISSN
- 2160-1836 (ISSN-L)
- PMC
- PMC5919727
- OpenAlex
- W2745099817
- Cited by
- 67
- References
- 1
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 19 · 2020: 6 · 2019: 5 · 2018: 2
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- G3 Genes Genomes Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Bangor University Research Portal (Bangor University) (submittedVersion, other-oa)
- Funders
- Leverhulme Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- genetic diversity, inbreeding, founder effect, genetic drift, genetic divergence, replication crisis, Mongolian gerbil, hamster, house mice, deer mouse, rats, next-generation sequencing
- MeSH terms
- Animals, Female, Genetics, Population, Gerbillinae, Cricetinae, Male, Polymorphism, Genetic, Genetic Variation, Animals, Inbred Strains, Founder Effect, Animals, Outbred Strains, Genetic Drift, Mice, Rats, High-Throughput Nucleotide Sequencing
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