Physiol. Genomics AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Physiol. Genomics (August 26, 2008). doi:10.1152/physiolgenomics.90237.2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
35/2/191    most recent
90237.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alam, I.
Right arrow Articles by Turner, C. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alam, I.
Right arrow Articles by Turner, C. H.
Submitted on May 2, 2008
Revised on August 20, 2008
Accepted on August 20, 2008

Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck

Imranul Alam1, Qiwei Sun1, Lixiang Liu1, Daniel L. Koller1, Yunlong Liu1, Howard J. Edenberg1, Michael J. Econs1, Tatiana Foroud1, and Charles H. Turner1*

1 Indiana University

* To whom correspondence should be addressed. E-mail: turnerch{at}iupui.edu.

Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans and animal models identified chromosomal regions linked to hip size and bone mass. Previously, we identified that the region of 4q21-q41 on rat chromosome (Chr) 4 harbors multiple femoral neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW) rats. The purpose of this study is to identify the candidate genes for femoral neck structure and density by correlating gene expression in the proximal femur with the femoral neck phenotypes linked to the QTLs on Chr 4. RNA was extracted from proximal femora of 4-week-old rats from F344 and LEW strains and two other strains, Copenhagen 2331 (COP) and Dark Agouti (DA), were used as a negative control. Microarray analysis was performed using Affymetrix Rat Genome 230 2.0 arrays. A total of 99 genes in the 4q21-q41 region were differentially expressed (p<0.05) among all strains of rats with a false discovery rate (FDR) less than 10%. These 99 genes were then ranked based on the strength of correlation between femoral neck phenotypes measured in F2 animals, homozygous for a particular strain's allele at the Chr 4 QTL, and the expression level of the gene in that strain. A total of 18 candidate genes were strongly correlated (r2>0.50) with femoral neck width and prioritized for further analysis. Quantitative PCR analysis confirmed 14 of 18 of the candidate genes. Ingenuity pathway analysis revealed several direct or indirect relationships among the candidate genes related to angiogenesis (VEGF), bone growth (FGF2), bone formation (IGF2 and IGF2BP3), and resorption ( TNF). This study provides a shortened list of genetic determinants of skeletal traits at the hip and may lead to novel approaches for prevention and treatment of hip fracture.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.