Table 1.
Key features of the population-based models discussed in this report.
| Human Cell Lines | Human Primary Cells | Mouse Populations | |
|---|---|---|---|
| Availability | Commercial Cell Repositories | 1) Commercial Blood Banks 2) Organ Donation 3) Surgical Waste Products 4) Long-Term Cultures from Commercial Cell Repositories |
Commercial Animal Vendors (i.e. Jackson Labs) |
| Availability of Genotype Data | Available for many of the lymphoblastoid cell lines (1000 Genomes Project) | This Approach Requires Genotyping | 1) Genotypes available for many of the inbred panels such as the Collaborative Cross and Mouse Diversity Panel 2) Diversity Outbred Population requires genotyping |
| Key Advantages | 1) Cell lines provide unlimited resource to test responses over longer-periods of time 2) Easily-obtainable 3) High-throughput capability 4) Genotyping not required |
1) Primary cells likely mirror human responses better than immortalized cell lines 2) Some cells can be easily-obtained through commercial sources 3) High-throughput capable |
1) Some genetic resource panels have already been genotyped 2) Genetic polymorphisms are better randomized in mouse populations as compared to human resulting in a great statistical power to detect association 3) Minor allele frequencies are lower in mouse populations providing the need to use less animals as compared to assaying the human population |
| Key Limitations | 1) Immortalized cells respond different than primary cells 2) In vitro conditions likely do not mirror in vivo conditions 3) Need for large numbers of individuals to make an association |
1) In vitro conditions likely do not mirror in vivo conditions 2) Need to acquire primary cells for each individual experiment 3) Need to genotype each individual 4) Need for large numbers of individuals to make an association 5) Individuals have differing background exposures, disease states, ages, sexes, etc. |
1) Toxicodynamic/Toxicokinetic differences between mice and human impact responses to chemicals 2) Need to maintain a mouse colony or purchase mice for each study 3) Some populations, such as the DO stock, require genotyping for each individual |