Functional & Integrative Genomics

, Volume 10, Issue 1, pp 63–72

Genes influencing spinal bone mineral density in inbred F344, LEW, COP, and DA rats

  • Imranul Alam
  • Qiwei Sun
  • Daniel L. Koller
  • Lixiang Liu
  • Yunlong Liu
  • Howard J. Edenberg
  • Tatiana Foroud
  • Charles H. Turner
Original Paper
  • 135 Downloads

Abstract

Previously, we identified the regions of chromosomes 10q12–q31 and 15p16–q21 harbor quantitative trait loci (QTLs) for lumbar volumetric bone mineral density (vBMD) in female F2 rats derived from Fischer 344 (F344) × Lewis (LEW) and Copenhagen 2331 (COP) × Dark Agouti (DA) crosses. The purpose of this study is to identify the candidate genes within these QTL regions contributing to the variation in lumbar vBMD. RNA was extracted from bone tissue of F344, LEW, COP, and DA rats. Microarray analysis was performed using Affymetrix Rat Genome 230 2.0 Arrays. Genes differentially expressed among the rat strains were then ranked based on the strength of the correlation with lumbar vBMD in F2 animals derived from these rats. Quantitative PCR (qPCR) analysis was performed to confirm the prioritized candidate genes. A total of 285 genes were differentially expressed among all strains of rats with a false discovery rate less than 10%. Among these genes, 18 candidate genes were prioritized based on their strong correlation (r2 > 0.90) with lumbar vBMD. Of these, 14 genes (Akap1, Asgr2, Esd, Fam101b, Irf1, Lcp1, Ltc4s, Mdp-1, Pdhb, Plxdc1, Rabep1, Rhot1, Slc2a4, Xpo4) were confirmed by qPCR. We identified several novel candidate genes influencing spinal vBMD in rats.

Keywords

Lumbar vBMD Gene expression Microarray QTLs Osteoporotic fracture 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Imranul Alam
    • 1
  • Qiwei Sun
    • 1
  • Daniel L. Koller
    • 2
  • Lixiang Liu
    • 2
  • Yunlong Liu
    • 3
  • Howard J. Edenberg
    • 4
  • Tatiana Foroud
    • 2
  • Charles H. Turner
    • 1
  1. 1.Department of Biomedical EngineeringIndiana University Purdue University IndianapolisIndianapolisUSA
  2. 2.Medical and Molecular GeneticsIndiana University Purdue University Indianapolis (IUPUI)IndianapolisUSA
  3. 3.Medicine, Indiana University Purdue University Indianapolis (IUPUI)IndianapolisUSA
  4. 4.Biochemistry and Molecular BiologyIndiana University Purdue University Indianapolis (IUPUI)IndianapolisUSA

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