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 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.
Alam
Imranul
I
Department of Biomedical Engineering, Indiana University Purdue University Indianapolis (IUPUI), Indianapolis, IN 46202-5251, USA.
Sun
Qiwei
Q
Koller
Daniel L
DL
Liu
Lixiang
L
Liu
Yunlong
Y
Edenberg
Howard J
HJ
Li
Jiliang
J
Foroud
Tatiana
T
Turner
Charles H
CH
D000465:Algorithms; D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D016000:Cluster Analysis; D019295:Computational Biology; D003433:Crosses, Genetic; D005260:Female; D005269:Femur / Q000378:metabolism*; D015870:Gene Expression; D053263:Gene Regulatory Networks; D008040:Genetic Linkage; D005819:Genetic Markers; D016678:Genome; D005838:Genotype; D006720:Homozygote; D046228:Microarray Analysis; D018895:Microsatellite Repeats; D005810:Multigene Family; D010641:Phenotype; D040641:Quantitative Trait Loci; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013314:Stress, Mechanical
D005819:Genetic Markers; D012333:RNA, Messenger; D012313:RNA