Differentially expressed genes strongly correlated with femur strength in rats

Alam, Imranul; Sun, Qiwei; Koller, Daniel L.; Liu, Lixiang; Liu, Yunlong; Edenberg, Howard J.; Li, Jiliang; Foroud, Tatiana; Turner, Charles H.

doi:10.1016/j.ygeno.2009.05.008

Cited by 13 publications

(11 citation statements)

References 44 publications

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“…A previous gene expression profiling study identified SEC23IP as an important mediator of bone formation and metabolism (29). Interestingly, 3 of the top candidate genes from that study ( IFIT3, SEC23IP , and PPP2R2D ) were also found to be among the most differentially expressed between NM and SSM in our study.…”

Section: Discussionmentioning

confidence: 99%

Integrative Genomics Identifies Molecular Alterations that Challenge the Linear Model of Melanoma Progression

et al. 2011

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Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N ¼ 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM. Cancer Res; 71(7); 2561-71. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Integrative Genomics Identifies Molecular Alterations that Challenge the Linear Model of Melanoma Progression

et al. 2011

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“…However, apparent craniofacial symptoms were not observed in p125 KO mice, which suggests that the Xenopus and mammalian p125s may have somewhat different physiological functions. Mircoarray analysis has suggested a correlation of the expression level of p125 and femur strength in rats (47) . This possibility should be examined in future studies.…”

Section: Introductionmentioning

confidence: 99%

The intracellular phospholipase A1 protein family

Tani

Kogure

Inoue

2012

BioMolecular Concepts

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Phospholipase A1 is an enzyme that hydrolyzes phospholipids, producing 2-acyl-lysophospholipids and fatty acids. The intracellular phospholipase A1 (iPLA1) protein family is a relatively recently discovered lipid-metabolizing enzyme family. Lower eukaryotes, such as yeasts and nematodes, and plants have only one iPLA1 protein, whereas mammals have three iPLA1 family proteins (PA-PLA1/DDHD1/iPLA1α, p125/Sec23IP/iPLA1β and KIAA0725p/DDHD2/iPLA1γ). Mammalian iPLA1 proteins are localized in different cellular compartments, and two of them, p125 and KIAA0725p, have been implicated in membrane trafficking events. Recent gene targeting studies on several organisms showed that iPLA1 family proteins are involved in various physiological functions, including plant shoot gravitropism, epithelial stem cell differentiation and spermiogenesis. In this review, we describe the features of iPLA1 family proteins and recent progress regarding our understanding of their physiological functions.

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“…Although these inbred rat models have served an important role in genetic mapping for bone fragility phenotypes, most of these quantitative trait loci (QTLs) encompass 20 to 30 cM and harbor hundreds of potential candidate genes. Subsequently, using genomic expression analysis, we identified several potential candidate genes within some of these QTLs . However, it is a formidable challenge to narrow these critical QTL regions to a small chromosomal segment containing a few genes.…”

Section: Introductionmentioning

confidence: 99%

High-Resolution Genome Screen for Bone Mineral Density in Heterogeneous Stock Rat

Alam

Koller

Cañete

et al. 2014

Journal of Bone and Mineral Research

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We previously demonstrated that skeletal mass, structure and biomechanical properties vary considerably in heterogeneous stock (HS) rat strains. In addition, we observed strong heritability for several of these skeletal phenotypes in the HS rat model, suggesting that it represents a unique genetic resource for dissecting the complex genetics underlying bone fragility. The purpose of this study was to identify and localize genes associated with bone mineral density in HS rats. We measured bone phenotypes from 1524 adult male and female HS rats between 17 to 20 weeks of age. Phenotypes included DXA measurements for bone mineral content and areal bone mineral density for femur and lumbar spine (L3-5), and volumetric BMD measurements by CT for the midshaft and distal femur, femur neck and 5th lumbar vertebra. A total of 70,000 polymorphic SNPs distributed throughout the genome were selected from genotypes obtained from the Affymetrix rat custom SNPs array for the HS rat population. These SNPs spanned the HS rat genome with a mean linkage disequilibrium coefficient between neighboring SNPs of 0.95. Haplotypes were estimated across the entire genome for each rat using a multipoint haplotype reconstruction method, which calculates the probability of descent for each genotyped locus from each of the 8 founder HS strains. The haplotypes were tested for association with each bone density phenotype via a mixed model with covariate adjustment. We identified quantitative trait loci (QTLs) for bone mineral density phenotypes on chromosomes 2, 9, 10 and 13 meeting a conservative genome-wide empiric significance threshold (FDR=5%; P<3 × 10−6). Importantly, most QTLs were localized to very small genomic regions (1-3 Mb), allowing us to identify a narrow set of potential candidate genes including both novel genes and genes previously shown to have roles in skeletal development and homeostasis.

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Differentially expressed genes strongly correlated with femur strength in rats

Cited by 13 publications

References 44 publications

Integrative Genomics Identifies Molecular Alterations that Challenge the Linear Model of Melanoma Progression

Integrative Genomics Identifies Molecular Alterations that Challenge the Linear Model of Melanoma Progression

The intracellular phospholipase A1 protein family

High-Resolution Genome Screen for Bone Mineral Density in Heterogeneous Stock Rat

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