Differentially expressed genes strongly correlated with femur strength in rats

The region of chromosome 1q33–q54 harbors quantitative trait loci (QTL) for femur strength in COP × DA and F344 × LEW F2 rats. The purpose of this study is to identify the genes within this QTL region that contribute to the variation in femur strength. Microarray analysis was performed using RNA extracted from femurs of COP, DA, F344 and LEW rats. Genes differentially expressed in the 1q33–q54 region among these rat strains were then ranked based on the strength of correlation with femur strength in F2 animals derived from these rats. A total of 214 genes in this QTL region were differentially expressed among all rat strains, and 81 genes were found to be strongly correlated (r2 > 0.50) with femur strength. Of these, 12 candidate genes were prioritized for further validation, and 8 of these genes (Ifit3, Ppp2r5b, Irf7, Mpeg1, Bloc1s2, Pycard, Sec23ip, and Hps6) were confirmed by quantitative PCR (qPCR). Ingenuity Pathway Analysis suggested that these genes were involved in interferon alpha, nuclear factor-kappa B (NFkB), extracellular signal-related kinase (ERK), hepatocyte nuclear factor 4 alpha (HNF4A) and tumor necrosis factor (TNF) pathways.