(To view the Health Monitoring Program Description and Reports, Click Here.)
Genetic Quality and Colony Management
Genetic drift describes random fluctuations in the numbers of gene variants in a population. This takes place when the occurrence of variant forms of a gene, called alleles, increases and decreases by chance over time. These variations in the presence of alleles are measured as changes in allele frequencies. In inbred models, where each individual animal is 99.9% genetically identical to other animals in the colony, genetic drift happens very slowly. In outbred models, genetic drift can happen more rapidly due to constantly changing allelic frequencies in a heterogeneous population of animals. Genetic drift is a basic mechanism of evolution and is nearly impossible to halt completely; however, there are breeding tactics that can be employed to slow or manage genetic drift in rodent colonies.
Harlan Laboratories has initiated a genetic recycling program for select models, including Hsd:Sprague Dawley® SD®, RccHan®:WIST, C57BL/6NHsd, BALB/cAnNHsd, C57BL/6JOlaHsd, and BALB/cOlaHsd. For each of these models, a Source Colony has been rederived and is currently housed in flexible-film isolators in either Livermore, California or Gannat, France. These Source Colonies will be used to repopulate Barrier Foundation Colonies (inbred) or Barrier Founder Colonies (outbred) on a regular basis to ensure that animals will be genetically consistent both within and across Barriers globally. The first models to be recycled, the C57BL/6OlaHsd and BALB/cOlaHsd colonies in the Netherlands and the United Kingdom, begins in Q3/4 2014.
For more information on our Genetic Recycling program, please contact Harlan’s Global Manager of Genetic Quality and Breeding at 800.473.6423800.473.6423
, ext. 19532 (North America) or +1 317.806.6080+1 317.806.6080
, ext. 19532 (EU and Asia).
Genetic Quality Control
Genetic monitoring is an essential part of inbred colony quality control. 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, Harlan Laboratories uses SNP analysis because of the combination of speed, efficiency and sensitivity at detecting genetic contamination of inbred lines.
It should be noted that currently available methods of monitoring are relatively insensitive at detecting genetic drift because they sample only a small portion of the genome. To rule out genetic drift, the full genome would have to be sequenced for all animals. All vendor programs for genetic monitoring currently are designed to detect genetic contamination, not genetic drift.
Prevention of Genetic Contamination
Preventing genetic contamination due to accidental mismating is the first priority for a genetic quality control program. Procedures such as room coat color separation, pest control, and exclusion methods are employed to minimize this risk. Animal care technicians are trained to recognize and report phenotypic deviations. Harlan regularly monitors growth data and production indices that are specific to each model (i.e., detailed production records, pedigrees, and cage cards) to ensure the consistency of our models.
Inbred Routine Genetic Monitoring
Harlan Laboratories’ global routine genetic monitoring program consists of collecting tissue samples quarterly from all new pedigreed Foundation Colony breeding cages in non-isolator-bred colonies. Tests are conducted on all pedigreed Foundation Colony breeding cages in newly-populated isolator-bred colonies, and then five (5) new foundation colony breeder cages annually thereafter.
Tissue samples are sent to the Harlan laboratory located at the Bionomics Research and Technology Center (BRTC) in Piscataway, New Jersey. The Harlan laboratory employs a customized panel of single nucleotide polymorphisms (SNPs) to evaluate strain differences in both rats and mice. Our routine rat and mouse SNP panels consist of 48 markers. Analysis is performed by utilizing allelic discrimination technology in a fully automated fashion. Our laboratory includes high throughput liquid handling robots that can process up to 500,000 SNPs daily.
Outbred Genetic Monitoring
Harlan performs routine global genetic monitoring on select outbred stocks, including Hsd:Sprague Dawley® SD®, Hsd:Athymic nude Foxn1rnu, Hsd:LE, RccHan®:WIST, Hsd:ICR(CD-1®), and Hsd:Athymic nude Foxn1nu. These stocks are tested at all locations to compare allelic frequencies both within and between colonies. Forty-eight (48) tissue samples per colony are tested using a panel of 96 SNP markers.