Determinants of QTL mapping power in the realized Collaborative Cross

Autor: Keele, Gregory R., Crouse, Wesley L., Kelada, Samir N. P., Valdar, William
Rok vydání: 2018
Předmět:
Collaborative Cross Mice
MPP
recombinant inbred lines
Quantitative Trait Loci
Population structure
allelic series
Context (language use)
Computational biology
QH426-470
Quantitative trait locus
Biology
Genome
Chromosomes
quantitative trait
Mice
03 medical and health sciences
haplotype association
0302 clinical medicine
Gene Frequency
Multiparental Populations
Genetics
Animals
Genetics(clinical)
Reference population
Molecular Biology
Alleles
Crosses
Genetic
Genetics (clinical)
030304 developmental biology
0303 health sciences
Models
Genetic
multiparent advanced generation inter-cross
Strain (biology)
multiparental population
Chromosome Mapping
Reproducibility of Results
MAGIC
Power (physics)
Power analysis
R package
Genetics
Population
Phenotype
Haplotypes
complex trait
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: G3: Genes|Genomes|Genetics
G3: Genes, Genomes, Genetics, Vol 9, Iss 5, Pp 1707-1727 (2019)
DOI: 10.1101/459966
Popis: The Collaborative Cross (CC) is a mouse genetic reference population whose range of applications includes quantitative trait loci (QTL) mapping. The design of a CC QTL mapping study involves multiple decisions, including which and how many strains to use, and how many replicates per strain to phenotype, all viewed within the context of hypothesized QTL architecture. Until now, these decisions have been informed largely by early power analyses that were based on simulated, hypothetical CC genomes. Now that more than 50 CC strains are available and more than 70 CC genomes have been observed, it is possible to characterize power based on realized CC genomes. We report power analyses from extensive simulations and examine several key considerations: 1) the number of strains and biological replicates, 2) the QTL effect size, 3) the presence of population structure, and 4) the distribution of functionally distinct alleles among the founder strains at the QTL. We also provide general power estimates to aide in the design of future experiments. All analyses were conducted with our R package, SPARCC (Simulated Power Analysis in the Realized Collaborative Cross), developed for performing either large scale power analyses or those tailored to particular CC experiments.
Databáze: OpenAIRE
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