RGD Reference Report - Identification of genes influencing skeletal phenotypes in congenic P/NP rats. - Rat Genome Database

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

Authors: Alam, I  Carr, LG  Liang, T  Liu, Y  Edenberg, HJ  Econs, MJ  Turner, CH 
Citation: Alam I, etal., J Bone Miner Res. 2010 Jan 8.
RGD ID: 2317896
Pubmed: PMID:20200994   (View Abstract at PubMed)
PMCID: PMC3153136   (View Article at PubMed Central)
DOI: DOI:10.1002/jbmr.8   (Journal Full-text)

We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-non-preferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22-q34 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 co-segregate with genes that regulate alcohol preference. The aim of this study is to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome (Chr) 4 QTL into P background (P.NP) significantly decreased areal (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of P Chr 4 QTL into 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 (r(2) > 0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), alpha synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using quantitative real-time PCR (q-PCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism, involving beta-estradiol, interferon gamma 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. (c) 2010 American Society for Bone and Mineral Research.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Iusm:PRatWeight Loss  IAGP as compared to NP/IusmRGD 
NP.P-(D4Rat119-D4Rat55)/IusmRatWeight Loss  IAGP as compared to NP/IusmRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Iusm:PRatdecreased body weight  IAGP as compared to NP/IusmRGD 
NP.P-(D4Rat119-D4Rat55)/IusmRatdecreased body weight  IAGP as compared to NP/IusmRGD 
P.NP-(D4Rat119-D4Rat55)/IusmRatdecreased bone mineral density  IAGP as compared to P/IusmRGD 
Iusm:PRathyperactivity  IAGP as compared to NP/IusmRGD 
NP.P-(D4Rat119-D4Rat55)/IusmRathyperactivity  IAGP as compared to NP/IusmRGD 
P.NP-(D4Rat119-D4Rat55)/IusmRatincreased body weight  IAGP as compared to P/IusmRGD 
Iusm:PRatincreased bone mineral density  IAGP compared to NP/IusmRGD 
NP.P-(D4Rat119-D4Rat55)/IusmRatincreased bone mineral density  IAGP as compared to P/IusmRGD 
Iusm:PRatincreased bone strength  IAGP as compared to NP/IusmRGD 

Objects Annotated

Strains
Iusm:P  (alcohol-preferring)
NP.P-(D4Rat119-D4Rat55)/Iusm  (NA)
P.NP-(D4Rat119-D4Rat55)/Iusm  (NA)

Objects referenced in this article
QTL Alc18 Alcohol consumption QTL 18 Rattus norvegicus

Additional Information