Microbial Status and Genetic Evaluation of Mice and Rats Proceedings of the 1999 US/Japan Conference (2000) / Chapter Skim
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Genetic Evaluation of Outbred Rats from the Breeder's Perspective
Genetic Evaluation of Outbred Rats from the Breeder's Perspective
Pages 51-64
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From page 51... ...
It was considered more important simply to begin breeding in a way that was not purposeful inbreeding with the hope that heterozygosity would be maintained. Unfortunately, the current interest in preserving and perhaps increasing heterozygosity in outbred populations, as well as addressing random genetic drift, is "historically" 51
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From page 52... ...
Worldwide, pharmaceutical and contract research organizations consume more than 70% of all commercially produced laboratory animals including rats. Because this demand will likely continue, we need to manage and genetically monitor outbred animals and, in particular, outbred rats correctly.
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From page 53... ...
To interpret information gathered from phenotype assessment of outbred populations using biochemical, immunologic, or DNA makers, it is necessary to view this information as a whole and to consider not only sim~lanties but also differences in the marker profiles. This inclusive information can best be obtained through the calculation of certain genetic monitoring statistics such as fixation index, estimate of polymorphism, conformity to Hardy-Weinberg equilibnum, and an estimate of average heterozygosity (Hartle 1988~.
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From page 54... ...
The second method is natural selection, which probably has a limited role in laboratory populations especially when rearing practices and the environment are relatively constant. The third method is unconscious selection wherein future breed selection is biased unconsciously by practices such as preferentially breeding good-tempered animals, animals with large litter size, or animals with lack of runted offspring.
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From page 55... ...
Another common error that produces nonrepresentative sampling is using entire litters as breed stock when forming a new colony. In addition, if a foundation colony that is linked to subpopulations by a regular migration process of breeders is not present, selection of a single production colony as a source of breed stock for a new colony may also misrepresent the genetic diversity present in all of the production colonies being maintained by an institution or breeder 100 90 80 70 60 50 40 30 20 10 o inbred coefficient (°/0)
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From page 56... ...
In constructing our foundation colony-orientated outbred production system for CD rats, we began by identifying the 27 existing colonies of these animals worldwide and examining their stocking and production histories. To preserve the maximum amount of genetic diversity, we searched for colonies that had been separated for at least 5 to 10 years and found eight colonies that had been separated from each other (no infusion of new breed stock)
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From page 57... ...
Pups were obtained by hysterotomy under aseptic conditions using a dual laminar flow hood technique. Rederived pups were aseptically transferred into 3-foot semirigid isolators and cross-fostered onto lactating females of defined flora status (Charles River A1tered Schaedler Flora [CRASFj)
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From page 58... ...
Each isolator contained up to 13 cages of breeding pairs, 12 cages holding future breed and stock, and two cages holding animals used for health monitoring of the isolator. In the case of the CD IGS foundation colony, the 20 isolators produce weanlings each week that are used for future breed replacement, forward migration, colony setup, and limited sale of overproduction for specialized customer use (Figure 7~.
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From page 59... ...
This process links all of the colonies to the foundation colony proactively making corrections without waiting for genetic monitoring to detect drift and a course of action to be undertaken. Unlike some migration systems, the genetic management of outbred foundation colonies by our company also includes backward migration (in-migration)
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From page 60... ...
Replacement breeders are then introduced into the foundation colony (Figure 11~. This process of in-migration helps maintain genetic diversity in the foundation colony and ensures that the foundation colony reflects the variation found in the production colonies.
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From page 61... ...
| Japan it= North America ~ = Forward migration, Replace 25% of production male breeders with foundation stock males = Individual production colonies FIGURE 10 IGS: Forward migration—every 3 years. Europe ~ ' - HM | in QuaraIll;ine ~ > ~ Rederivation F-O s~ ~ ~ ~ ~ ~ ~ ~ ~ 88 ~ ~ 88 88 Wilmington IGS ' ' .
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From page 62... ...
Monitoring and management of outbred populations inevitably comes down to the issue of comparisons. It is unlikely that there is a single marker or set of markers, or a specific value in a population genetic statistic calculated from the frequencies of such markers, that can be used as an absolute cutoff in determining similarity of subpopulations.
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From page 63... ...
If you have an outbred stock such as Sprague Dawley or Wistar Han and you have 20 colonies (subpopulations) , they are all going to drift independently unless you migrate animals between them to make them one functional colony.
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From page 64... ...
This is an important point to consider even if biochemical markers are used. We are in the process of developing more effective DNA monitoring and results analysis techniques that should aid in comparison of genetic divergence between colonies.
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