Genetic integrity assurance program

Maintaining the genetic integrity of your research models is essential to minimize variability and improve reproducibility in your research experiments. At Envigo, we manage our models under the Genetic Integrity Assurance Program, which represents the most comprehensive and transparent program in the industry.

  • Robust colony management: Rely on our industry-standard breeding schemes along with robust operational procedures and internal quality auditing to minimize the genetic divergence of your models.
  • Genetic monitoring program: Benefit from our extensive Genetic Monitoring Program and gain a transparent view of our operations.
  • Genetic drift management program: Trust in a more consistent model as we address the natural mechanism of cumulative genetic drift with a routine colony refreshing program.

It’s important to fully understand how a laboratory animal vendor ensures genetic integrity to maintain quality control. Learn more about how our three-tiered strategy supports high quality standards in our rodent models.

Three-tiered strategy supports high quality standards in our rodent models

Colony management describes the breeding, husbandry, and
quality control program for managing colonies of rodents.
A breeding scheme is the system of mating a succession
of generations. There are many different mating systems or breeding
schemes, depending on the desired result, such as preserving
or controlling the genetic causes of variability in traits of interest.
Genetic monitoring is the process of detecting a change
in a species, which can be performed by evaluating genetic
markers in DNA. Genetic monitoring is important for quality
control in inbred lines of research animals to maintain consistency.
Over time, a natural accumulation of spontaneous,
random genetic mutations occurs in populations of both inbred
and outbred rodent colonies. This tendency for genes to evolve
is called genetic drift.

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Breeding inbred strains
The three groups of inbred coloniesTo reduce the potential for spontaneous mutations becoming fixed in an inbred colony, Envigo breeds inbred strains using a pyramid mating system. The structure of inbred colonies consists of three groups: the Foundation Colony (FC), Pedigreed Expansion Colony (PEC) and the Production Colony (PC). Breeders for the FC only come from the FC while breeders for the PEC only come from the FC. Breeders for the PC can come from the FC and the PEC but never from the PC.  This breeding methodology reduces the chance of cumulative genetic drift because spontaneous mutations are more likely to occur on the larger PC where they would be eliminated within one generation.

Breeding outbred stocks
In contrast to inbred strains, outbred stocks must be bred to maintain maximum heterogeneity.   Envigo employs a Poiley1 rotational breeding system in barrier-bred rodent models to ensure that only unrelated animals are mated together. This system reduces the inbreeding coefficient within each colony and limits cumulative genetic drift by preventing genetic bottlenecks.

Example of a 4-Section Poiley Rotational Breeding System

Example of a 4-Section Poiley rotational breeding system:  Females from Section A are mated to males from Section B. Their offspring are assigned to Section C.  Females from Section B are mated to males from Section C.  Their offspring are assigned to Section D, etc.  By using the Poiley Rotational Breeding System, each generation of animals are rotated throughout different sections in the colony to ensure a low inbreeding coefficient. .

(1) Poiley, S.M. (1960). A systematic method for breeder rotation for inbred laboratory animal colonies. Proc Anim Care Pan 10, 159–166.

If a model is produced by sibling matings for more than
20 consecutive generations, it is considered inbred. Inbred
strains are considered nearly genetically identical.
Spontaneous mutation is a naturally occurring change in
the DNA sequence that makes up a gene, resulting in a
variant form that may be transmitted to subsequent generations.
An outbred stock is a closed population for at least four
generations of genetically variable animals bred to
maintain maximum heterozygosity.
The process of selectively mating animal models in
rotation to minimize inadvertent bias in the outbred
breeding as described in: Poiley S. M. 1960. A systematic
method of breeder rotation for non-inbred laboratory animal
colonies. Anim. Care Panel 10:15-166.
A barrier is a facility that houses rodents in which
there is a systematic, comprehensive program for the
prevention of pathogen contamination.
Genetic bottlenecking refers to losing genetic variation
when a population’s size is reduced.

Understanding the essentials: Genetic monitoring is an essential part of maintaining the genetic integrity of animal models. Genetic monitoring programs are employed for the detection of genetic contamination or bottlenecking, but are not designed to detect genetic drift due to spontaneous mutations. Several methods of genetic monitoring are available, including biochemical markers, phenotypic analysis, and, more recently, microsatellite DNA and single nucleotide polymorphism (SNP) analysis. While each method has its advantages, Envigo uses SNP analysis because of the combination of speed, efficiency and accuracy at detecting genetic contamination.

Monitoring for consistency: Envigo regularly monitors production indices that are specific to each model (i.e., detailed production records, pedigrees, and cage cards) to ensure operational consistency in breeding our models. Technicians are also trained to identify and report phenotypic deviants.

SNP analysis: Testing is performed at the Bionomics Research and Technology Center (BRTC) at Rutgers University, a world-renowned genomics laboratory, which uses high-throughput liquid handling robot technology to evaluate the genetic integrity of Envigo’s rat and mouse colonies globally.

Testing inbred models: Using a custom panel of 48 single nucleotide polymorphism (SNP) markers, all new barrier-bred foundation colony (FC) cages are tested quarterly. All isolator bred foundation colonies are tested annually (five inbred isolator cages per FC).

Testing outbred models: Using a custom panel of 96 single nucleotide polymorphism (SNP) markers, colonies are tested from select models annually. These models include Hsd:Sprague Dawley® SD®, Hsd:RH Foxn1rnu, HsdBlu:LE, RccHan®:WIST, Hsd:ICR(CD-1®), and Hsd:Athymic nude-Foxn1nu.

Current routine genetic monitoring reports can be found on our genetic monitoring reports page.

A phenotype a set of observable characteristics resulting
from a genotype.
A short sequence of DNA consisting of multiple repetitions
of a set of two to nine base pairs, used as a genetic marker
when individuals differ in the number of repetitions.
A SNP is a variation in a single nucleotide that occurs
at a specific position in the genome, where each variation
is present to some appreciable degree within a population.
A pedigree is the record of descent, generally used to
track the ancestry of inbred mouse colonies.

Understanding the essentials: Genetic drift describes fluctuations in the numbers of gene variants in a population that can be caused by various mechanisms, such as spontaneous mutation, bottlenecking, and migration. Many of these genetic alterations are in regions of non-coding DNA. A smaller but significant change could occur in protein-coding regions of the genome and potentially could alter the gene expression, which may lead to a change in the gene function and/or phenotype. 

Genetic Drift Management at Envigo
Envigo uses a colony refreshing program with cryopreserved embryos from a single source. Here, a single source colony is used to replace all foundation colony breeders every two years in our C57BL/6NHsd, BALB/cAnNHsd, C57BL/6JOlaHsd and BALB/cOlaHsd inbred mouse models. Embryos are cryopreserved from the Source Colony every two years and used to completely replace the Source Colony two years later, just prior to the next round of foundation colony replacements. C57BL/6JOlaHsd and BALB/cOlaHsd foundation colonies in Europe and Israel will be refreshed between the 2nd and 3rd quarter of 2018.  C57BL/6NHsd and BALB/cAnNHsd foundation colonies will be refreshed in North America and Europe in 2019.

Genetic migration or gene flow is the transfer of gene or
alleles (alternative forms of a gene that are found at the
same place on a chromosome) from one population to another.
In laboratory animal colonies, this occurs when the wrong
stock or strain of animals are mated together, resulting in
a genetic contamination.

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