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Note to the Reader: Published winter 2003 in Neuroinformatics Volume 1, Issue 4, pps. 343-358 (ISSN 1539-2791).

PDF Version
Genetic Correlates of Gene Expression in Recombinant Inbred Strains: A Relational Model System to Explore Neurobehavioral Phenotypes


Elissa  J.  Chesler  (Department of Anatomy and Neurobiology, Center for Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, TN) 
Jintao  Wang  (Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY) 
Lu  Lu  (Department of Anatomy and Neurobiology, Center for Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, TN) 
Yanhua  Qu  (Department of Anatomy and Neurobiology, Center for Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, TN) 
Kenneth  F.  Manly  (Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY) 
Robert W. Williams  (Department of Anatomy and Neurobiology, Center for Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, TN) 
 

Full genome sequencing, high-density genotyping, expanding sets of microarray assays, and systematic phenotyping of neuroanatomical and behavioral traits are producing a wealth of data on the mouse central nervous system (CNS). These disparate resources are still poorly integrated. One solution is to acquire these data using a common reference population of isogenic lines of mice, providing a point of integration between the data types. Recombinant inbred (RI) mice, derived through inbreeding of progeny from an inbred cross, are a powerful tool for complex trait mapping and analysis of the challenging phenotypes of neuroscientific interest. These isogenic RI lines are a retrievable genetic resource that can be repeatedly studied using a wide variety of assays. Diverse data sets can be related through fixed and known genomes, using tools such as the interactive webbased system for complex trait analysis, www.WebQTL.org. In this report, we demonstrate the use of WebQTL to explore complex interactions among a wide variety of traits­ from mRNAtranscripts to the impressive behavioral and pharmacological variation among RI strains. The relational approach exploiting a common set of strains facilitates study of multiple effects of single genes (pleiotropy) without a priori hypotheses required. Here we demonstrate the power of this technique through genetic correlation of gene expression with a database of neurobehavioral phenotypes collected in these strains of mice through more than 20 years of experimentation. By repeatedly studying the same panel of mice, early data can be re-examined in light of technological advances unforeseen at the time of their initial collection.

 


   


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