Identification of genes influencing skeletal phenotypes in congenic P/NP rats

Imranul Alam, Lucinda G. Carr, Tiebing Liang, Yunlong Liu, Howard Edenberg, Michael Econs, Charles H. Turner

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-nonpreferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22 and 4q34 for alcohol preference. At the same location, several QTLs linked to bone density and structure were detected in Fischer 344 (F344) and Lewis (LEW) rats, suggesting that bone mass and strength genes might cosegregate with genes that regulate alcohol preference. The aim of this study was to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome 4 QTL into the P background (P.NP) significantly decreased areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of the P chromosome 4 QTL into the NP background (NP.P) significantly increased bone mineral content (BMC) and aBMD in the same skeletal sites. Microarray analysis from the femurs using Affymetrix Rat Genome arrays revealed 53 genes that were differentially expressed among the rat strains with a false discovery rate (FDR) of less than 10%. Nine candidate genes were found to be strongly correlated (r2>0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), α synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using real-time quantitative PCR (qPCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism involving β-estradiol, interferon-γ, and a voltage-gated calcium channel. We identified several candidate genes, including some novel genes on chromosome 4 segregating for skeletal phenotypes in reciprocal congenic P and NP rats.

Original languageEnglish
Pages (from-to)1314-1325
Number of pages12
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume25
Issue number6
DOIs
StatePublished - Jun 2010

Fingerprint

Phenotype
Bone Density
Genes
Chromosomes, Human, Pair 4
Quantitative Trait Loci
Alcohols
sepiapterin reductase
Bone and Bones
Synucleins
Neuropeptide Y
Calcium Channels
Microarray Analysis
Femur
Interferons
Real-Time Polymerase Chain Reaction
Estradiol
Genome

Keywords

  • Bone mass
  • Congenic
  • Gene
  • Neuropeptide Y
  • QTL

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{b06947d468c34bfba3e164747c7ec65a,
title = "Identification of genes influencing skeletal phenotypes in congenic P/NP rats",
abstract = "We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-nonpreferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22 and 4q34 for alcohol preference. At the same location, several QTLs linked to bone density and structure were detected in Fischer 344 (F344) and Lewis (LEW) rats, suggesting that bone mass and strength genes might cosegregate with genes that regulate alcohol preference. The aim of this study was to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome 4 QTL into the P background (P.NP) significantly decreased areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of the P chromosome 4 QTL into the NP background (NP.P) significantly increased bone mineral content (BMC) and aBMD in the same skeletal sites. Microarray analysis from the femurs using Affymetrix Rat Genome arrays revealed 53 genes that were differentially expressed among the rat strains with a false discovery rate (FDR) of less than 10{\%}. Nine candidate genes were found to be strongly correlated (r2>0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), α synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using real-time quantitative PCR (qPCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism involving β-estradiol, interferon-γ, and a voltage-gated calcium channel. We identified several candidate genes, including some novel genes on chromosome 4 segregating for skeletal phenotypes in reciprocal congenic P and NP rats.",
keywords = "Bone mass, Congenic, Gene, Neuropeptide Y, QTL",
author = "Imranul Alam and Carr, {Lucinda G.} and Tiebing Liang and Yunlong Liu and Howard Edenberg and Michael Econs and Turner, {Charles H.}",
year = "2010",
month = "6",
doi = "10.1002/jbmr.8",
language = "English",
volume = "25",
pages = "1314--1325",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Identification of genes influencing skeletal phenotypes in congenic P/NP rats

AU - Alam, Imranul

AU - Carr, Lucinda G.

AU - Liang, Tiebing

AU - Liu, Yunlong

AU - Edenberg, Howard

AU - Econs, Michael

AU - Turner, Charles H.

PY - 2010/6

Y1 - 2010/6

N2 - We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-nonpreferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22 and 4q34 for alcohol preference. At the same location, several QTLs linked to bone density and structure were detected in Fischer 344 (F344) and Lewis (LEW) rats, suggesting that bone mass and strength genes might cosegregate with genes that regulate alcohol preference. The aim of this study was to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome 4 QTL into the P background (P.NP) significantly decreased areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of the P chromosome 4 QTL into the NP background (NP.P) significantly increased bone mineral content (BMC) and aBMD in the same skeletal sites. Microarray analysis from the femurs using Affymetrix Rat Genome arrays revealed 53 genes that were differentially expressed among the rat strains with a false discovery rate (FDR) of less than 10%. Nine candidate genes were found to be strongly correlated (r2>0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), α synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using real-time quantitative PCR (qPCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism involving β-estradiol, interferon-γ, and a voltage-gated calcium channel. We identified several candidate genes, including some novel genes on chromosome 4 segregating for skeletal phenotypes in reciprocal congenic P and NP rats.

AB - We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-nonpreferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22 and 4q34 for alcohol preference. At the same location, several QTLs linked to bone density and structure were detected in Fischer 344 (F344) and Lewis (LEW) rats, suggesting that bone mass and strength genes might cosegregate with genes that regulate alcohol preference. The aim of this study was to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome 4 QTL into the P background (P.NP) significantly decreased areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of the P chromosome 4 QTL into the NP background (NP.P) significantly increased bone mineral content (BMC) and aBMD in the same skeletal sites. Microarray analysis from the femurs using Affymetrix Rat Genome arrays revealed 53 genes that were differentially expressed among the rat strains with a false discovery rate (FDR) of less than 10%. Nine candidate genes were found to be strongly correlated (r2>0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), α synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using real-time quantitative PCR (qPCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism involving β-estradiol, interferon-γ, and a voltage-gated calcium channel. We identified several candidate genes, including some novel genes on chromosome 4 segregating for skeletal phenotypes in reciprocal congenic P and NP rats.

KW - Bone mass

KW - Congenic

KW - Gene

KW - Neuropeptide Y

KW - QTL

UR - http://www.scopus.com/inward/record.url?scp=77953499068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953499068&partnerID=8YFLogxK

U2 - 10.1002/jbmr.8

DO - 10.1002/jbmr.8

M3 - Article

C2 - 20200994

AN - SCOPUS:77953499068

VL - 25

SP - 1314

EP - 1325

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 6

ER -