Genome Reshuffling for Advanced Intercross Permutation (GRAIP): Simulation and Permutation for Advanced Intercross Population Analysis

摘要: Background: Advanced intercross lines (AIL) are segregating populations created using a multi-generation breeding protocol for fine mapping complex trait loci (QTL) in mice and other organisms. Applying QTL methods backcross populations, often followed by na ve permutation of individuals phenotypes, does not account the effect AIL family structure which final generations have been expanded leads to inappropriately low significance thresholds. The critical problem with approaches is that individual an exchangeable unit. Methodology/Principal Findings: has immediate implications optimal creation (many crosses, few animals per cross, population expansion before generation) we discuss these utility mapping. We also describe Genome Reshuffling Intercross Permutation, (GRAIP) method analyzing data accounts structure. GRAIP permutes more interchangeable unit generation crosses - parental genome simulating regeneration permuted based on exchanged identities. determines appropriate genome-wide thresholds locus-specific Pvalues AILs similar structures. Wemore » contrast large densely genotyped mouse (1333 from 32 crosses). A coat color as model phenotype demonstrates high false-positive locus identification uncertain levels, corrected GRAIP. detects established hippocampus weight new locus, Hipp9a. Conclusions Significance: populations.« less