Strain Background and Genetic Drift
- What is the genetic background of this strain?
- What is the right control for this mouse?
- I’m not sure about the purity of the background of my mouse strain. What can I do?
- What is the difference between inbred and outbred mice? Inbred and outbred nude mice?
- What is genetic drift?
- How do I detect genetic drift?
- How do I prevent genetic drift?
- What is the difference between C57BL/6J and C57BL/6N? Or BALB/c and BALB/cByJ? What are substrains?
- Do I really need to backcross my mutant to the inbred line to “refresh” it?
Please refer to the “Detail section of the strain datasheet. The way the strain was made will be in the Development section. The background information can also sometimes be clarified by viewing “Control Suggestions.”
Additionally, the nomenclature may offer some clues:
This can be a challenging situation. You could
- Backcross your strain ~10 times to your desired genetic background. A Genome Scan might help improve the speed at which this can be done, but may be limited in generating reliable data.
- Build your controls into your colony’s breeding plan
- Consider running a high density GigaMUGA analysis which may help in identifying what mouse genetic backgrounds are present.
An inbred strain is one that:
- is produced using at least 20 consecutive generations of sister x brother or parent x offspring matings, or;
- is traceable to a single ancestral pair in the 20th or subsequent generation.
An outbred mouse stock is a closed population (for at least four generations) of genetically variable animals that is bred to maintain maximum heterozygosity.
An inbred mouse has more genetic uniformity than an outbred mouse.
The following definition comes from the online book “Mouse Genetics” by Lee Silver (1995):
“The constant tendency of genes to evolve even in the absence of selective forces. Genetic drift is fueled by spontaneous neutral mutations that disappear or become fixed in a population at random.”
This includes a variety of possible mutations including single base changes, deletions, duplications, or inversions in the DNA.
Detection of genetic drift requires comparison of whole genome sequence data; this is typically not a cost-effective option for most labs. Drift cannot be detected using Single Nucleotide Polymorphism (SNP) scans.
Many times drift is detected through the observation of phenotypic differences; however, often drift does not produce a visible or detectable phenotype and may go undetected.
Genetic drift is a spontaneous biological process that cannot be stopped. The potential deleterious impacts of drift on research can be minimized through the following practices:
- Maintain pedigrees lines and detailed colony records
- Watch for phenotypic changes in mutants and controls
- Refresh breeders frequently (~every 10 generations)
- Avoid selection pressure (choose breeders at random)
- Cryopreserve unique strains
8. What is the difference between C57BL/6J and C57BL/6N? Or BALB/c and BALB/cByJ? What are substrains?
A substrain is a strain that
- has been bred apart from the parental inbred strain for 20 generations;
- has any known, fixed genetic difference, even if that difference is only at one gene;
- has phenotypic differences with the parent colony are discovered.
- See also: Three Ways a B6J Mouse Differs from B6N and Why it Should Matter to Your Research, and BALB/cJ and BALB/cByJ: How can I choose? I’m so confused!
Genetic drift is an issue with mutant mouse strains. Refreshing your colony by backcrossing for a couple of generations to the parent inbred strain, or ordering new breeders from the vendor, can reduce the number of spontaneous mutations that may have accumulated
- Link to On-Demand Webinar on Achieving Reproducible Mouse Studies
- Information on the Patented Genetic Stability Program (GSP)
- Why it Took 2 Years for a Harvard Research Lab to Get Back to Research (Genetic Drift article)
- Three Ways a B6J Mouse Differs from B6N and Why it Should Matter to Your Research
- BALB/cJ and BALB/cByJ: How Can I Choose? I’m So Confused!
- There is no such thing as a C57BL/6 mouse!
- How substrains arise
- A tool for telling apart C57BL/6J versus C57BL/6N substrains