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 s...

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Bibliographic Details
Published in:Genetics (Austin) 2006-03, Vol.172 (3), p.1783-1797
Main Authors: Valdar, William, Flint, Jonathan, Mott, Richard
Format: Article
Language:English
Subjects:
Animals
Chromosomes
Computer Simulation
Confidence intervals
Crosses, Genetic
Design
Epistasis, Genetic
Genetic diversity
Genetic Drift
Genetic Markers
Genomics
Haplotypes
Inbreeding
Investigations
Mice
Mice, Inbred A
Mice, Inbred AKR
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Inbred DBA
Models, Genetic
Physical Chromosome Mapping - methods
Population
Quantitative Trait Loci
Studies
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Summary: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.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1534/genetics.104.039313