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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
1P01AG014731-01A1
Application #
6098770
Study Section
Project Start
1999-02-01
Project End
2000-01-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Sandri, M; Barberi, L; Bijlsma, A Y et al. (2013) Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology 14:303-23
Ramamurthy, B; Larsson, L (2013) Detection of an aging-related increase in advanced glycation end products in fast- and slow-twitch skeletal muscles in the rat. Biogerontology 14:293-301
Sloane, Lauren B; Stout, Joseph T; Austad, Steven N et al. (2011) Tail tendon break time: a biomarker of aging? J Gerontol A Biol Sci Med Sci 66:287-94
Sloane, Lauren B; Stout, Joseph T; Vandenbergh, David J et al. (2011) Quantitative trait loci analysis of tail tendon break time in mice of C57BL/6J and DBA/2J lineage. J Gerontol A Biol Sci Med Sci 66:170-8
Lionikas, Arimantas; Carlborg, Orjan; Lu, Lu et al. (2010) Genomic analysis of variation in hindlimb musculature of mice from the C57BL/6J and DBA/2J lineage. J Hered 101:360-7
Lang, Dean H; Conroy, David E; Lionikas, Arimantas et al. (2009) Bone, muscle, and physical activity: structural equation modeling of relationships and genetic influence with age. J Bone Miner Res 24:1608-17
Blizard, David A; Lionikas, Arimantas; Vandenbergh, David J et al. (2009) Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences. Physiol Genomics 36:158-66
Foreman, J E; Lionikas, A; Lang, D H et al. (2009) Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice. Genes Brain Behav 8:714-27
Norman, Holly; Zackrisson, Håkan; Hedström, Yvette et al. (2009) Myofibrillar protein and gene expression in acute quadriplegic myopathy. J Neurol Sci 285:28-38
Cristea, A; Korhonen, M T; Hakkinen, K et al. (2008) Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single-fibre levels in elite master sprinters. Acta Physiol (Oxf) 193:275-89

Showing the most recent 10 out of 48 publications