International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 113 -  GENETIC ANALYSIS OF GENE EXPRESSION IN MOUSE CNS REVEALS MAJOR PLEIOTROPIC AND POLYGENIC CONTROL OF SYNAPTIC MACHINERY.

Chesler EJ 1, Baldwin NE 2, Zhang B 3, Kirov S 3, Wang J 1, Lu L 1, Snoddy JR 3, Langston MA 2, Manly KF 1, Williams RW 1

1 Center for Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, TN, United States, 2 Department of Computer Science, University of Tennessee, Knoxville, TN, United States,

3 Oak Ridge National Laboratory, Oak Ridge, TN, United States

In our ongoing microarray-based analysis of genetic regulation of gene transcription in recombinant inbred strains generated by crossing

C57BL/6J and DBA/2J (BXD RI), we have identified a small number of chromosomal loci that modulate mRNA abundance of several hundred transcripts each. These loci were detected using a novel application of clique analysis for dimension reduction of microarray data. Many of these results can be explored using new tools and external links in WebQTL (www.webqtl.org/search.html), which allows users to rapidly examine multiple traits and interpret their relations and patterns of covariance. Using a combination of genetic correlation analysis, clique analysis, Quantitative trait locus (QTL) analysis, and Gene Ontology category representation analysis, we have identified loci that modulate expression of components of the synaptic vesicle cycling system.  Using Batch Sequence Analysis, we have identified putative novel conserved regulatory sequences for one highly co-regulated group of transcripts. Specific candidate genes that reside at some of these regulatory loci have been identified. A single locus has been identified that regulates the transcription of over 1500 transcripts. The synaptic vesicle structure and function is dependent on a large number of cytoskeletal, anchoring, motor and fusion proteins. Vesicle mediated transport, exocytosis and endocytosis are major means of effecting and controlling cell-cell communication in the CNS. Other related cellular processes that rely on the same gene networks are similarly varied. Genetic variation also affects mRNA translocation, and possibly synaptic gene expression mechanisms. The relationship of these cliques of genetically correlated transcript abundances to systems level phenotypes such as ethanol withdrawal severity demonstrates the utility of this mouse reference population for systems biological research.

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