Simulating the collaborative cross: power of quantitative trait loci detection and mapping resolution in large sets of recombinant inbred strains of mice.
It has been suggested that the collaborative cross, a large set of recombinant inbred strains derived from eight inbred mouse strains, would be a powerful resource for the dissection of complex phenotypes. Here we use simulation to investigate the power of the collaborative cross to detect and map small genetic effects. We show that for a fixed population of 1000 individuals, 500 RI lines bred using a modified version of the collaborative cross design are adequate to map a single additive locus that accounts for 5% of the phenotypic variation to within 0.96 cM. In the presence of strong epistasis more strains can improve detection, but 500 lines still provide sufficient resolution to meet most goals of the collaborative cross. However, even with a very large panel of RILs, mapping resolution may not be sufficient to identify single genes unambiguously. Our results are generally applicable to the design of RILs in other species.
Valdar
William
W
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom. valdar@well.ox.ac.uk
Flint
Jonathan
J
Mott
Richard
R
D000818:Animals; D003198:Computer Simulation; D003433:Crosses, Genetic; D004843:Epistasis, Genetic; D040961:Genetic Drift; D005819:Genetic Markers; D006239:Haplotypes; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008957:Models, Genetic; D020161:Physical Chromosome Mapping / Q000379:methods*; D040641:Quantitative Trait Loci
D005819:Genetic Markers