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doi:10.1534/genetics.104.038174
A more recent version of this article appeared on November 1, 2005.
REGULAR RESEARCH PAPERS |
Expression Quantitative Trait Loci Analysis of 13 Genes in the Rat Prostate
Satoshi Yamashita 1, Kuniko Wakazono 1, Tomoko Nomoto 1, Yoshimi Tsujino 1, Takashi Kuramoto 1 and Toshikazu Ushijima 1*
1 National Cancer Center Research Institute
* To whom correspondence should be addressed. E-mail: tushijim{at}ncc.go.jp.
Submitted on November 5, 2004
Revised on December 2, 2004
Accepted on 29 July 2005
Differential expression of mRNA among animal strains is one of the mechanisms for their diversity. cDNA microarray analysis of the prostates of BUF/Nac (BUF) and ACI/N (ACI) rats, which show different susceptibility to prostate cancers, found 195 differentially expressed genes. To identify loci that control differential expression of 13 genes with diverse expression levels, their expression levels were measured by quantitative RT-PCR in 89 backcross rats, and expression quantitative trait locus (eQTL) analysis was performed. Nine genes (Aldh1a1, Aldr1, Bmp6, Cdkn1a (p21), Cntn6, Ghr, Jund, Nupr1, and RT1-M3) were controlled by cis-acting loci. Cdkn1a, a cell cycle regulator and a candidate for a prostate cancer susceptibility gene, was mapped to its own locus, and had polymorphisms, including a 119-bp insertion in the 5' upstream region in BUF rats. Four genes (Kclr, Pbsn, Psat1, and Ptn) were controlled by trans-acting loci. Pbsn, a prostate-specific gene on chr. X, was controlled by a QTL on chr. 8. Depending upon which gene we selected from the genes widely used for normalization (Actb, Gapd, or Ppia), different QTLs were mapped for Kclr, Psat1, and Ptn. Normalization using Actb most appropriately explained the expression levels in a congenic strain for chr. 3. eQTL analysis with precise measurement of expression levels and appropriate normalization was shown to be effective to map loci that control gene expression in vivo.
Key Words: Actb, Cdkn1a, gene expressions, quantitative trait loci, rat prostate
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