Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of rat chromosome 4 for skeletal traits at femoral neck

ABSTRACT: Femoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats; Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Previously, we identified that the region of 4q21-q41 on chromosome (Chr) 4 uniquely harbors multiple femoral neck quantitative trait loci (QTLs) in inbred Fischer 344 (F344) and Lewis (LEW) rats. In this study we identified the candidate genes for femoral neck density and structure by correlating gene expression in the proximal femur with the femoral neck phenotypes linked to the QTLs on Chr 4. Microarray analysis was performed using RNA extracted from proximal femora of 4-week-old rats from F344, LEW and two other strains. A total of 104 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 104 genes were then ranked based on the proportion of variation in femoral neck phenotypes in F2 animals homozygous for a particular strainâ??s allele at the Chr 4 QTL explained by the expression level of the gene in that strain. A total of 37 genes, including 21 candidate genes and 16 predicted genes, were strongly correlated (r2>0.50) with different femoral neck phenotypes and prioritized for further analysis. Ingenuity pathway analysis revealed several direct or indirect relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, interleukin 6, insulin growth factor 2, androgen receptor and tumor necrosis factor. Experiment Overall Design: Comparison of differentially expressed genes at the chromosome 4 QTL identified in F344 and LEW F2 rats.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Charles Turner

PROVIDER: E-GEOD-11180 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Bone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats; Genetic mapping in alcohol-preferring (P) and alcohol-non-preferring (NP) rats has identified a major quantitative trait locus (QTL) in the region between q22 â?? q34 on chromosome (Chr) 4 for alcohol preference. In a separate genome-wide linkage study, using inbred Fischer 344 (F344) and Lewis (LEW) rats, several QTL linked to bone density and structure were identified at the same location suggesting that bone mass and strength genes might co-segregate with genes that regulate the alcohol preference trait. The aim of this study is to identify the genes segregating for skeletal phenotypes and alcohol trait in congenic P/NP rats. We compared bone mineral content (BMC), areal/volumetric bone mineral density (aBMD/vBMD) and biomechanical strength at different skeletal sites from 6-month-old inbred and congenic P/NP rats. Transfer of the NP Chr 4 QTL into P background significantly increased body weight but decreased BMC, aBMD/vBMD in whole body, cranium, femur, and lumbar vertebrae. On the other hand, transfer of P Chr 4 QTL into NP background significantly decreased body weight but increased BMC and aBMD in the same skeletal sites. Microarray analysis was performed from the femurs of 4-week-old rats (n = 5 per strain) using Affymetrix Rat Genome 230 2.0 arrays. A total of 53 genes, including 41 candidate genes and 12 predicted genes, were differentially expressed among all strains of rats with a false discovery rate (FDR) less than 10%. Several candidate genes from microarray analysis were found to be were strongly correlated (r2>0.50) with different skeletal phenotypes. Gene expression of top 3 candidate genes from microarray profiling was validated by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, tumor necrosis factor and androgen receptor. Experiment Overall Design: Comparison of differentially expressed genes between 4q22-4q34 on chromosome 4 in NP, P, NP.P and P.NP rats.

Project description:Bone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats Genetic mapping in alcohol-preferring (P) and alcohol-non-preferring (NP) rats has identified a major quantitative trait locus (QTL) in the region between q22 – q34 on chromosome (Chr) 4 for alcohol preference. In a separate genome-wide linkage study, using inbred Fischer 344 (F344) and Lewis (LEW) rats, several QTL linked to bone density and structure were identified at the same location suggesting that bone mass and strength genes might co-segregate with genes that regulate the alcohol preference trait. The aim of this study is to identify the genes segregating for skeletal phenotypes and alcohol trait in congenic P/NP rats. We compared bone mineral content (BMC), areal/volumetric bone mineral density (aBMD/vBMD) and biomechanical strength at different skeletal sites from 6-month-old inbred and congenic P/NP rats. Transfer of the NP Chr 4 QTL into P background significantly increased body weight but decreased BMC, aBMD/vBMD in whole body, cranium, femur, and lumbar vertebrae. On the other hand, transfer of P Chr 4 QTL into NP background significantly decreased body weight but increased BMC and aBMD in the same skeletal sites. Microarray analysis was performed from the femurs of 4-week-old rats (n = 5 per strain) using Affymetrix Rat Genome 230 2.0 arrays. A total of 53 genes, including 41 candidate genes and 12 predicted genes, were differentially expressed among all strains of rats with a false discovery rate (FDR) less than 10%. Several candidate genes from microarray analysis were found to be were strongly correlated (r2>0.50) with different skeletal phenotypes. Gene expression of top 3 candidate genes from microarray profiling was validated by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, tumor necrosis factor and androgen receptor. Keywords: Comparison of gene expression profiles between NP, P, NP.P and P.NP rats

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Transcription profiling of rat chromosome 4 for skeletal traits at femoral neck

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