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POSTER 67 - THE INTEGRATION OF FUNCTIONAL GENOMICS AND QTL ANALYSIS
R Hitzemann
Oregon Health & Sciences
University
2) Williams R,
1) Reed C
1)Oregon Health & Sciences
University, 2) University of Tennessee Health Sciences Center
Data have been obtained for gene expression (Affymetrix -U74aV2 array) for 9 inbred mouse strains (C57BL/6, DBA/2, LP, BALB/c, C3H, CBA, A, AKR and 129/Sv) in whole brain (N=6/strain) and in two discrete brain areas, the dorsomedial straitum and central extended amygdala (CeA+BSTLP)(N=3/strain, bold strains). Of the 12488 genes or transcripts found on the U74aV2 array, 6357 were scored as present in all nine strains. The ANOVA for the whole brain data revealed 851, 1135 and 1480 genes or transcripts differentially expressed at p < 10-7, 10-6 and 10-5, respectively. Comparison of the whole brain and discrete brain regions, revealed some similar and different patterns of gene expression. For example, as reported by Sandberg et al. (2000), GIRK3 (Kcnj9) shows a lower expression level in the B6 strain across all regions. The expression data were used to create chromosome gene expression maps which were then compared with the QTL maps for three phenotypes: basal locomotor activity, ethanol-induced locomotor activity and haloperidol-induced catalepsy. QTL maps were available for the 6 F2 intercrosses possible from the bold strains and for two heterogenous stock populations. For basal activity, strong candidate quantitative trait genes (QTGs) include Kcnj9 and Rgs5. Previously suggested QTG candidates for ethanol response (Bdnf) and haloperidol response (Drd2) were eliminated. Supported by AA 11034, 13484, MH 51372 and the VA Research Service.
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