Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways

Obesity-related diseases are poised to become the primary cause of death in developed nations. While a number of monogenic causes of obesity have recently been identified, these are responsible for only a small proportion of human cases of obesity. Quantitative trait locus (QTL) studies using animal models have revealed hundreds of potential loci that affect obesity; however, few have been further analyzed beyond the original QTL scan. We previously mapped four QTL in an F2 between divergently selected Fat (F) and Lean (L) lines. A QTL of large effect on chromosome 15 ( Fob3) was subsequently mapped to a higher resolution into two smaller-effect QTL ( Fob3a and Fob3b) using crosses between the F-line and a congenic line containing L-line alleles at the Fob3 QTL region. Here we report the gene expression characterization of Fob3b. Microarray expression analysis using the NIA-NIH 15K cDNA array set containing 14,938 mouse ESTs was employed to identify candidate genes and pathways that are differentially expressed between the F-line and a congenic line containing only the Fob3b QTL ( Fob3b-line). Our study suggests squalene epoxidase (Sqle), a cholesterol biosynthesis enzyme, as a strong positional candidate gene for Fob3b. Several other cholesterol biosynthesis pathway genes unlinked to Fob3b were found to be differentially expressed, suggesting that a perturbation of this pathway could be in part responsible for the phenotypic difference between the F-line and Fob3b-line mice.

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Gene expression analysis of 1,25(OH)2 D3 -dependent differentiation of HL-60 cells: a cDNA array study

British Journal of Haematology ◽

10.1046/j.1365-2141.2002.03734.x ◽

2002 ◽

Vol 118 (4) ◽

pp. 1065-1070 ◽

Cited By ~ 30

Author(s):

Hakan Savli ◽

Yan Aalto ◽

Bálint Nagy ◽

Sakari Knuutila ◽

Seppo Pakkala

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Cdna Array

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Fine Mapping and Positional Candidate Gene Analysis of Chromosome 3p21 in Inflammatory Bowel Disease: Association with CCR5 Δ32

Clinical Science ◽

10.1042/cs098016pc ◽

2000 ◽

Vol 98 (s42) ◽

pp. 16P-17P

Author(s):

JD Simmons ◽

M Parkes ◽

J Satsangi ◽

KI Welsh ◽

DP Jewell

Keyword(s):

Inflammatory Bowel Disease ◽

Candidate Gene ◽

Fine Mapping ◽

Bowel Disease ◽

Disease Association ◽

Gene Analysis ◽

Positional Candidate Gene ◽

Positional Candidate ◽

Inflammatory Bowel ◽

Chromosome 3P21

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Isolation of differentially expressed genes in wheat caryopses with contrasting starch granule size

Open Life Sciences ◽

10.2478/s11535-013-0127-z ◽

2013 ◽

Vol 8 (3) ◽

pp. 297-305

Author(s):

Rita Armonienė ◽

Kristina Jonavičienė ◽

Vytautas Ruzgas ◽

Gintaras Brazauskas

Keyword(s):

Gene Expression ◽

Winter Wheat ◽

Differentially Expressed Genes ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Starch Granule ◽

Wheat Breeding ◽

Granule Size ◽

Differentially Expressed ◽

Breeding Lines

AbstractIn order to identify genes responsible for starch granule initiation during early development of wheat caryopsis, nine winter wheat breeding lines were studied. Two breeding lines, which are the most diverse in A-type granule size (26.85 µm versus 23.65 µm) were chosen for further differential gene expression analysis in developing caryopses at 10 and 15 days post-anthesis (DPA). cDNA-amplified fragment length polymorphism (cDNA-AFLP) analysis resulted in 384 transcript-derived fragments, out of which 18 were identified as being differentially expressed. Six differentially expressed genes, together with the six well-known starch biosynthesis genes, were chosen for semi-quantitative gene expression analysis in developing wheat caryopses at 10 and 15 DPA. This study provides genomic information on 18 genes differentially expressed at early stages of wheat caryopses development and reports on the identification of genes putatively involved in the production of large A-type granules. These genes are targets for further validation on their role in starch granule synthesis control and provide the basis for the development of DNA marker tools in winter wheat breeding for enhanced starch quality.

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Fine mapping of a QTL for ear size on porcine chromosome 5 and identification of high mobility group AT-hook 2 (HMGA2) as a positional candidate gene

Genetics Selection Evolution ◽

10.1186/1297-9686-44-6 ◽

2012 ◽

Vol 44 (1) ◽

pp. 6 ◽

Cited By ~ 20

Author(s):

Pinghua Li ◽

Shijun Xiao ◽

Na Wei ◽

Zhiyan Zhang ◽

Ruihua Huang ◽

...

Keyword(s):

Candidate Gene ◽

Fine Mapping ◽

High Mobility ◽

High Mobility Group ◽

Positional Candidate Gene ◽

Porcine Chromosome ◽

Chromosome 5 ◽

Positional Candidate

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Analysis of a positional candidate gene for inflammatory bowel disease: NRAMP2

Inflammatory Bowel Diseases ◽

10.1002/ibd.3780060205 ◽

2007 ◽

Vol 6 (2) ◽

pp. 92-98 ◽

Cited By ~ 9

Author(s):

Pieter C. F. Stokkers ◽

Kees Huibregtse ◽

A. C. Leegwater ◽

Pieter H. Reitsma ◽

Guido N. J. Tytgat ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Candidate Gene ◽

Bowel Disease ◽

Positional Candidate Gene ◽

Positional Candidate ◽

Inflammatory Bowel

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Global Gene Expression Analysis Demonstrates that Transforming Growth Factor β1 (TGF-β1) Signals Exclusively through Receptor Complexes Involving TGF-β Receptor I and Identifies Numerous Targets of TGF-β Signaling.

Blood ◽

10.1182/blood.v104.11.2178.2178 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2178-2178

Author(s):

Goran Karlsson ◽

Yingchun Liu ◽

Marie-José Goumans ◽

Jonas Larsson ◽

Ju-Seog Lee ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Target Genes ◽

Global Gene Expression ◽

Differentially Expressed ◽

Global Gene Expression Analysis ◽

Β Receptor ◽

Tgf Β1

Abstract In the hematopoietic system, TGF-β1 is one of the most potent extrinsic regulators, affecting both early progenitors and committed cells. At the top of the hematopoietic hierarchy, TGF-β1 maintains hematopoietic stem cells (HSCs) in quiescence in vitro through transcriptional regulation of genes encoding proteins important in the cell cycle. We have shown that TGF-β receptor I (TβRI) −/− HSCs exhibit increased proliferative capacity in vitro and that TβRII−/− mice develop a multifocal autoimmune disease, mainly mediated by T-cells (Larsson et al, 2003, Levéen et al 2002). The mechanisms of TGF-β signaling in hematopoietic cells are poorly understood and many target genes of TGF-β signaling remain elusive. In this study we have used global gene expression analysis to investigate whether all TGF-β signaling is mediated by TβRI and II. Furthermore, we asked what target genes are affected upon TGF-β stimulation in normal and TGF-β signaling deficient murine embryonic fibroblasts (MEFs). MEFs were grown with and without TGF-β1 stimulation and proliferation, transcriptional responses and expression analysis were performed. We demonstrate through Western Blot analysis, luciferase reporter assays and cell expansion experiments how these cells lack functional TβRI. Additionally, transcriptional assays show that no other Smad activity is triggered by TGF-β1 stimulation. Furthermore, we demonstrate through quantitative RT-PCR that the inhibitor of differentiation family of genes, known targets of TGF-β signaling, are not affected by TGF-β1 in TβRI−/− MEFs, while wt cells downregulate these genes 4–8.5 fold in response to stimulation. In order to completely exclude alternative receptors outside the TGF-β superfamily and signaling pathways activated through TβRII alone, we performed global gene expression profiling on TGF-β1 stimulated TβRI−/− MEFs with unstimulated TβRI deficient cells as reference. Very few (0.05 %) of the more than 37,000 spots on the microarray had a >2 fold differential expression in the two experiments conducted. Similar experiments performed on wt cells resulted in differential expression of between 2.6–3.9 % of the genes printed. From this data we conclude that no signaling affecting gene expression occur in the absence of TβRI in these cells. Additionally we present transcriptional profiles of MEF cell lines that either are normal or are TβRI deficient. By means of cDNA microarray technology, we have identified genes that were differentially expressed when TβRI deficient fibroblasts were compared to wt cells stimulated with TGF-β1. Our results create a data base of 461 significantly differentially expressed (p<0.01) target genes of TGF-β signaling. These include genes potentially responsible for the growth arrest induced by TGF-β1, like Gadd45g, Gas5, Id1, Id2 and Id3. However, the most significantly enriched number of differentially expressed genes are involved in protein folding and chaperone activities (Hspa9a, Hsp105, Hspe1, Hsp60, Cct2, Cct3, Cct8, Tcp1 and Dnaja1. Studies to identify TGF-β signaling responsive genes in HSCs are in progress.

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Genome-wide Association Study Identified the BCL11B Gene as a Positional Candidate Gene Affecting GPT Levels in Pigs

Journal of Agriculture & Life Science ◽

10.14397/jals.2014.48.4.197 ◽

2014 ◽

Vol 48 (4) ◽

pp. 197-205

Author(s):

Jae-Bong Lee ◽

◽

Beom-Mo Kim ◽

Chae-Kyoung Yoo ◽

Hee-Bok Park ◽

...

Keyword(s):

Association Study ◽

Candidate Gene ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Positional Candidate Gene ◽

Positional Candidate ◽

Genome Wide

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Demonstration of diet-induced decoupling of fatty acid and cholesterol synthesis by combining gene expression array and 2H2O quantification

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00436.2011 ◽

2012 ◽

Vol 302 (2) ◽

pp. E209-E217 ◽

Cited By ~ 11

Author(s):

Kristian K. Jensen ◽

Stephen F. Previs ◽

Lei Zhu ◽

Kithsiri Herath ◽

Sheng-Ping Wang ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Expression Analysis ◽

Cholesterol Synthesis ◽

Gene Expression Analysis ◽

Cholesterol Biosynthesis ◽

Acid Synthesis ◽

Gene Expression Array ◽

Expression Array ◽

High Carbohydrate

The liver is a crossroad for metabolism of lipid and carbohydrates, with acetyl-CoA serving as an important metabolic intermediate and a precursor for fatty acid and cholesterol biosynthesis pathways. A better understanding of the regulation of these pathways requires an experimental approach that provides both quantitative metabolic flux measurements and mechanistic insight. Under conditions of high carbohydrate availability, excess carbon is converted into free fatty acids and triglyceride for storage, but it is not clear how excessive carbohydrate availability affects cholesterol biosynthesis. To address this, C57BL/6J mice were fed either a low-fat, high-carbohydrate diet or a high-fat, carbohydrate-free diet. At the end of the dietary intervention, the two groups received 2H2O to trace de novo fatty acid and cholesterol synthesis, and livers were collected for gene expression analysis. Expression of lipid and glucose metabolism genes was determined using a custom-designed pathway focused PCR-based gene expression array. The expression analysis showed downregulation of cholesterol biosynthesis genes and upregulation of fatty acid synthesis genes in mice receiving the high-carbohydrate diet compared with the carbohydrate-free diet. In support of these findings, 2H2O tracer data showed that fatty acid synthesis was increased 10-fold and cholesterol synthesis was reduced by 1.6-fold in mice fed the respective diets. In conclusion, by applying gene expression analysis and tracer methodology, we show that fatty acid and cholesterol synthesis are differentially regulated when the carbohydrate intake in mice is altered.

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