Alam Imranul, Sun Qiwei, Koller Daniel L, Liu Lixiang, Liu Yunlong, Edenberg Howard J, Li Jiliang, Foroud Tatiana, Turner Charles H
Department of Biomedical Engineering, Indiana University Purdue University Indianapolis (IUPUI), Indianapolis, IN 46202-5251, USA.
Genomics. 2009 Oct;94(4):257-62. doi: 10.1016/j.ygeno.2009.05.008. Epub 2009 May 29.
The region of chromosome 1q33-q54 harbors quantitative trait loci (QTL) for femur strength in COPxDA and F344xLEW 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 (r(2)>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.
在COP×DA和F344×LEW F2大鼠中,1号染色体1q33 - q54区域含有影响股骨强度的数量性状基因座(QTL)。本研究的目的是确定该QTL区域内导致股骨强度变异的基因。使用从COP、DA、F344和LEW大鼠股骨中提取的RNA进行微阵列分析。然后,根据这些大鼠衍生的F2动物中与股骨强度的相关强度,对这些大鼠品系中在1q33 - q54区域差异表达的基因进行排名。在所有大鼠品系中,该QTL区域共有214个基因差异表达,发现81个基因与股骨强度高度相关(r²>0.50)。其中,12个候选基因被优先进行进一步验证,通过定量PCR(qPCR)证实了其中8个基因(Ifit3、Ppp2r5b、Irf7、Mpeg1、Bloc1s2、Pycard、Sec23ip和Hps6)。 Ingenuity通路分析表明,这些基因参与了α干扰素、核因子-κB(NFkB)、细胞外信号调节激酶(ERK)、肝细胞核因子4α(HNF4A)和肿瘤坏死因子(TNF)通路。