Studying complex biological systems using multifactorial perturbation

Replication in genetic studies of complex traits

“…Examples include certain statistical designs that enrich for cosegregation, population structure, ascertainment, and measurement scale. In contrast, use of scale transformations may destroy true biological interactions (Jansen 2003).…”

“…More extended applications of animal models will also be facilitated by future approaches, capable of linking information from phenotypes, segregating populations and gene expression microarrays, as well as gene annotations from databases (O'Brien & Woychik, 2003;Jansen & Nap, 2001;Quackenbush, 2001;Jansen et al 2002;Kell, 2002;Jansen, 2003;Darvasi, 2003;Perez-Enciso et al 2003;Schadt et al 2003). However, the use of animal models is not without problems as the same heterogeneity issues reviewed above are also present in comparative mapping, and may distort replication between human and animal data sets.…”

The Collaborative Cross, a community resource for the genetic analysis of complex traits

“…We believe that computational, statistical and genomic resources are now sufficiently mature to address these mechanisms in the context of an experimental model system that more accurately reflects the genetic structure of human populations 2,3 . Global analysis of complex biological systems can be implemented most efficiently using experimental designs that employ multifactorial perturbations 4,5 . A well-designed model-organism resource for a new synthetic phase of genetic studies will have a direct, positive and long-lasting impact on the diagnosis and treatment of common and chronic human disease, including cancer, pulmonary and cardiovascular diseases, obesity and diabetes, behavioral disorders and neurodegenerative diseases.…”

Wild-derived mouse stocks: an underappreciated tool for aging research

“…Instead, the construction of F2 intercross stocks (i.e., by crossing F1 hybrids) is needed since it results in a significant degree of genome reshuffling, thereby producing offspring with variable combinations of alleles (Jansen 2003). And, unlike F1 hybrids, which are heterozygous at all loci (except those that happen to be the same in each of the parental strains), F2 intercross stocks have three possible genotypes for each allele: (1) homozygous for parent A; (2) heterozygous; or (3) homozygous for parent B.…”