Phenomic analysis of the murine hippocampus

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DESCRIPTION (provided by applicant): The mouse and human genomes have now been sequenced, but the task of linking genes to functions is just beginning. We will combine old and new technologies as a generalized method of linking genetic loci to functions and also as a method of linking disparate functions to each other. The proposed project depends on the existence of resources that have been produced by mouse geneticists over the past century, including the numerous inbred, recombinant inbred (RI), consomic, and congenic strains. These resources are a rich source of genetic diversity that remains essentially untapped for studies of the central nervous system. In this project we will exploit this genetic diversity to begin to define the set of traits that comprise the "hippocampal phenotype," i.e., what might be termed the hippocampal "phenome." We call this approach a "phenomic analysis." This project will focus on traits that involve inter-strain variation in adult neurogenesis and in hippocampal morphology and development. The general strategy will be to: 1) Identify multiple genetic traits that vary among a set of inbred strains and to use network construction (i.e., a novel approach consisting of a collection of statistical methods and data visualization techniques) to generate hypotheses about the potential relationships among these diverse traits (Specific Aim 1); 2) exploit existing mouse genetic resources, i.e., RI strains and consomic strains, to test the hypotheses generated from the network analysis and simultaneously to map the genetic loci responsible for the identified traits (Specific Aim 2); and 3) to determine the developmental basis for the traits identified as significant and/or possible related from the network analysis of the traits identified in adult animals (Specific Aim 3). As described in Preliminary Results, we have made some progress towards each of these steps, and it is clear that there are numerous genetic traits that we will be able to study and map simultaneously. This "moderate throughput" approach, in effect, provides a genetic dissection of hippocampal structure, function, and development