The purpose of the QTL analysis Core is to provide a resource, common to all research components of the program, of centralized data management, organization and analysis of data to identify quantitative trait loci (QTLs) for age-related phenotypes, and assessment of QTL origins of genetic associations across time and among phenotypic domains. This Core will have the primary responsibility for integrating data from the multiple projects into a centralized database managed under a rigorous routine of data checking, cleaning, file maintenance, backup, and quality control. Analyses for the detection of QTLs will be undertaken using the RI sample to nominate QTLs using carefully specified criteria for significance designed to minimize false positive results. The F2 sample will be used as a replication to confirm nominated QTLs. The QTL analyses will be conducted at three ages representing key developmental phases of the mouse lifespan: 150, 450, and 750 days of age. Ten male and ten female mice from each of 22 recombinant inbred lines (and the two parental inbred lines) will be used to nominate QTLs. The replication sample will consist of 400 F2 animals (net, after loss due to death) derived from the same progenitor strains that were used to derive the RI lines at each of the three ages. Three phenotypic measures will be obtained at each measurement occasion on non-destructive measures in F2 animals to minimize the effect of intra-individuals variability and to enhance the power to detect QTL effects. Interval QTL mapping will be conducted using existing software routines. A regression model is described for analyzing data across time points to test for QTL effects that are common to all time points or unique to a particular time point. The QTL Analysis Core will provide a resource for integrated data management and QTL analyses across all phenotypic domains of the program project.
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