Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 62

While there is genetic diversity in the outbred stocks described above, over time the genetic diversity will decrease without a very large colony maintained by a careful breeding scheme to avoid inbreeding. In addition, because each mouse is unique, there are no relevant control animals or sequenced reference genomes. These factors present significant difficulties in using outbred stocks. To address these issues and further expand genetic diversity, another approach was taken in recent years. As described above, the Collaborative Cross strains were developed using a mix of eight inbred strains that represented the most genetic diversity possible with existing inbred strains at the time. In the process of producing these mice, an alternative approach was developed in which 144 partially inbred Collaborative Cross strains, at generations ranging from F4 to F12, were maintained by randomized outcrossing, to create a novel population of mice, the Diversity Outbred stock, in which each individual mouse had an equal amount of DNA from all the progenitor strains, but all in a unique mix [34]. Each mouse is phenotypically and genetically different from the next and resulting in a huge variation in phenotypes. Large SNP genotyping arrays make it possible to phenotype large numbers of these mice that share the same phenotype and identify the candidate genes that might cause the problem [35–37].

Nomenclature for the Diversity Outbred stocks follows that of outbred stocks, J:DO, where J is the breeder, The Jackson Laboratory in this example, and DO stands for Diversity Outbred.