Identification of age-dependent gene expression changes in rTg4510 females.

<p>(A) Animals available for analysis included age groups averaging 1.9 months, 4.7 months and 6.1 months, respectively. The 1.9 month old age group was only available for the rTg4510 genotype, while the other age groups were available for all genotypes. (B) Principle Component Analysis (PCA) of full genome expression data of all samples was used to identify any outliers in the sample set. One outlier (6.1 month tTA, not shown) was removed for all analyses. Samples are colored by age (green: 1.9 months; red: 4.7 months; blue: 6.1 months). Genotypes are represented by shapes (spheres: DN; pyramids: rTg4510; octahedra: tTA). (C) Principle Component Analysis (PCA) with samples colored by genotype (green: DN; blue: rTg4510; red: tTA) highlight differences amongst all three genotypes. (D) 447 probe sets were altered as a function of age in rTg4510 females (“rTg4510 Age”, 1-way ANOVA of 1.9, 4.7 and 6.1 month old rTg4510 females, FDR<0.05, no fold-change cutoff). 1523 probe sets were different between rTg4510 and tTA animals at 4.7 months (“rTg4510 vs tTA 4.7 mo”, 1-way ANOVA of 4.7 month old DN, tTA and rTg4510 females followed by Fisher’s Least Significant Difference [LSD] test comparing rTg4510 and tTA, FDR<0.05, no fold-change cutoff), while 2749 probe sets were different at 6.1 months (“rTg4510 vs tTA 6.1 mo”, 1-way ANOVA of 6.1 month-old DN, tTA and rTg4510 females followed by Fisher’s Least Significant Difference [LSD] test comparing rTg4510 and tTA, FDR<0.05, no fold-change cutoff). The intersection of these 3 datasets contained 165 probe sets, representing 139 genes, which define the genes that are significantly altered with age in rTg4510 animals compared to control tTA animals. A 2-way ANOVA to look at an interaction between age and genotype could not be used for this dataset because data for all age groups were not available for all genotypes. (E) Volcano plot of p-value versus fold change of all genes comparing 4.7 month old rTg4510 and tTA animals. The FDR<0.05 cutoff is indicated with a red line. (F) Volcano plot of p-value versus fold change of all genes comparing 6.1 month old rTg4510 and tTA animals. The FDR<0.05 cut-off is indicated with a red line.