Ultrafine mapping of Dyscalc1 to an 80-kb chromosomal segment on chromosome 7 in mice susceptible for dystrophic calcification.

Abstract:

:In mice, dystrophic cardiovascular calcification (DCC) is controlled by a major locus on proximal mouse chromosome 7 named Dyscalc1. Here we present a strategy that combines in silico analysis, expression analysis, and extensive sequencing for ultrafine mapping of the Dyscalc1 locus. We subjected 15 laboratory mouse strains to freeze-thaw injury of the heart, and association with respective genotypes allowed condensation of the Dyscalc1 locus to 1 Mb. Within this region, 51 known and predicted genes were studied in DCC-susceptible C3H/He and DCC-resistant C57BL/6 mice with respect to mRNA expression in response to injury. Five genes displayed differential expression. Genotyping of seven novel single nucleotide polymorphisms (SNPs) within these genes revealed an 80-Kb region in NZB mice that were found positive for calcification though carrying otherwise alleles from DCC-resistant mice. This microheterogeneity in NZB mice was evolutionary conserved in all DCC-susceptible mouse strains and contains the genes EMP-3, BC013491, and Abcc6 (partially). The flanking SNPs are rs3703247 and NT_039420.5_2757991. mRNA levels of EMP-3 were found to be upregulated in response to injury in both C57BL/6 and C3H/He mice. Sequencing of EMP-3 revealed an SNP leading to an amino acid substitution (p.T153I) that was found in all mouse strains susceptible for DCC but not in resistant strains such as C57BL/6 mice. Thus, the p.T153I changes might affect the biological function of EMP-3 gene product after injury. Using this combined approach, we ultrafine-mapped the Dyscalc1 locus to an 80-Kb region and identified EMP-3 as a new candidate gene for DCC.

journal_name

Physiol Genomics

journal_title

Physiological genomics

authors

Aherrahrou Z,Doehring LC,Kaczmarek PM,Liptau H,Ehlers EM,Pomarino A,Wrobel S,Götz A,Mayer B,Erdmann J,Schunkert H

doi

10.1152/physiolgenomics.00133.2006

subject

Has Abstract

pub_date

2007-01-17 00:00:00

pages

203-12

issue

2

eissn

1094-8341

issn

1531-2267

pii

00133.2006

journal_volume

28

pub_type

杂志文章
  • Iron-related transcriptomic variations in CaCo-2 cells, an in vitro model of intestinal absorptive cells.

    abstract::Regulation of iron absorption by duodenal enterocytes is essential for the maintenance of homeostasis by preventing iron deficiency or overload. Despite the identification of a number of genes implicated in iron absorption and its regulation, it is likely that further factors remain to be identified. For that purpose,...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00297.2005

    authors: Chicault C,Toutain B,Monnier A,Aubry M,Fergelot P,Le Treut A,Galibert MD,Mosser J

    更新日期:2006-06-16 00:00:00

  • Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage.

    abstract::The aim of the study was to explore the genetic architecture influencing weight of fast- and slow-twitch skeletal muscles. The weights of the slow-twitch soleus, the mixed gastrocnemius, the fast-twitch tibialis anterior (TA), and extensor digitorum longus (EDL) muscles were 11-34% greater (P < 0.001) in 200-day-old C...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00103.2003

    authors: Lionikas A,Blizard DA,Vandenbergh DJ,Glover MG,Stout JT,Vogler GP,McClearn GE,Larsson L

    更新日期:2003-12-16 00:00:00

  • Gene expression profile of zebrafish exposed to hypoxia during development.

    abstract::Understanding how vertebrates respond to hypoxia can have important clinical implications. Fish have evolved the ability to survive long exposure to low oxygen levels. However, little is known about the specific changes in gene expression that result from hypoxia. In this study we used a zebrafish cDNA microarray to e...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00128.2002

    authors: Ton C,Stamatiou D,Liew CC

    更新日期:2003-04-16 00:00:00

  • Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation.

    abstract::Mesodermal and epidermal precursor cells undergo phenotypic changes during differentiation to the smooth muscle cell (SMC) lineage that are relevant to pathophysiological processes in the adult. Molecular mechanisms that underlie lineage determination and terminal differentiation of this cell type have received much a...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00148.2004

    authors: Spin JM,Nallamshetty S,Tabibiazar R,Ashley EA,King JY,Chen M,Tsao PS,Quertermous T

    更新日期:2004-11-17 00:00:00

  • Therapeutic potential of microRNAs for the treatment of renal fibrosis and CKD.

    abstract::Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents sh...

    journal_title:Physiological genomics

    pub_type: 杂志文章,评审

    doi:10.1152/physiolgenomics.00039.2017

    authors: Lv W,Fan F,Wang Y,Gonzalez-Fernandez E,Wang C,Yang L,Booz GW,Roman RJ

    更新日期:2018-01-01 00:00:00

  • Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy.

    abstract::Autosomal recessive mandibuloacral dysplasia [mandibuloacral dysplasia type A (MADA); Online Mendelian Inheritance in Man (OMIM) no. 248370] is caused by a mutation in LMNA encoding lamin A/C. Here we show that this mutation causes accumulation of the lamin A precursor protein, a marked alteration of the nuclear archi...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00060.2005

    authors: Filesi I,Gullotta F,Lattanzi G,D'Apice MR,Capanni C,Nardone AM,Columbaro M,Scarano G,Mattioli E,Sabatelli P,Maraldi NM,Biocca S,Novelli G

    更新日期:2005-10-17 00:00:00

  • Cell dormancy plasticity: quiescence deepens into senescence through a dimmer switch.

    abstract::Both being dormant cellular states, quiescence and senescence are traditionally considered distinct. Quiescence is reversible to proliferation upon growth signals, whereas senescence is irreversible in physiological conditions. Recent findings, however, suggest that quiescence deepening with a decreased proliferative ...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00068.2020

    authors: Fujimaki K,Yao G

    更新日期:2020-11-01 00:00:00

  • Noninjurious mechanical ventilation activates a proinflammatory transcriptional program in the lung.

    abstract::Mechanical ventilation is a life-saving intervention in patients with respiratory failure. However, human and animal studies have demonstrated that mechanical ventilation using large tidal volumes (>or=12 ml/kg) induces a potent inflammatory response and can cause acute lung injury. We hypothesized that mechanical ven...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00027.2009

    authors: Gharib SA,Liles WC,Klaff LS,Altemeier WA

    更新日期:2009-05-13 00:00:00

  • Microarray analyses identify molecular biomarkers of Atlantic salmon macrophage and hematopoietic kidney response to Piscirickettsia salmonis infection.

    abstract::Piscirickettsia salmonis is the intracellular bacterium that causes salmonid rickettsial septicemia, an infectious disease that kills millions of farmed fish each year. The mechanisms used by P. salmonis to survive and replicate within host cells are not known. Piscirickettsiosis causes severe necrosis of hematopoieti...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00036.2004

    authors: Rise ML,Jones SR,Brown GD,von Schalburg KR,Davidson WS,Koop BF

    更新日期:2004-12-15 00:00:00

  • Cloning, tissue distribution, and functional expression of the human G protein beta 4-subunit.

    abstract::Heterotrimeric G proteins (Galphabetagamma) play an essential role in coupling membrane receptors to effector proteins such as ion channels and enzymes. Among the five mammalian Gbeta-subunits cloned, the human G protein beta4 has not been described. The purpose of the present study was to functionally characterize th...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00085.2001

    authors: Ruiz-Velasco V,Ikeda SR,Puhl HL

    更新日期:2002-02-11 00:00:00

  • A temporal study of gene expression in rat lung following fixed-volume hemorrhage.

    abstract::Previous studies have indicated that hemorrhage may predispose the lung to respiratory distress syndrome. Gene expression profiling with oligonucleotide microarrays was used to evaluate the genetic responses of the lung to hemorrhage. Conscious rats, chronically instrumented with a catheter and telemetry device to rec...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00075.2005

    authors: Bowman PD,Sondeen JL,Zhao B,Coppes VG,Nelson JJ,Dubick MA,Vaughan GM

    更新日期:2005-11-17 00:00:00

  • Detection of SNP epistasis effects of quantitative traits using an extended Kempthorne model.

    abstract::Epistasis effects (gene interactions) have been increasingly recognized as important genetic factors underlying complex traits. The existence of a large number of single nucleotide polymorphisms (SNPs) provides opportunities and challenges to screen DNA variations affecting complex traits using a candidate gene analys...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00096.2006

    authors: Mao Y,London NR,Ma L,Dvorkin D,Da Y

    更新日期:2006-12-13 00:00:00

  • Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis.

    abstract::In recent years, it has become evident that the adult mammalian CNS contains a population of neural stem cells (NSCs) described as immature, undifferentiated, multipotent cells, that may be called upon for repair in neurodegenerative and demyelinating diseases. NSCs may give rise to oligodendrocyte progenitor cells (O...

    journal_title:Physiological genomics

    pub_type: 杂志文章,评审

    doi:10.1152/physiolgenomics.00021.2002

    authors: Imitola J,Snyder EY,Khoury SJ

    更新日期:2003-08-15 00:00:00

  • Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis.

    abstract::Although some single polymorphism analyses of the angiotensinogen (AGT) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single-nucleotide polymorphisms (SNPs) (...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00133.2003

    authors: Wu SJ,Chiang FT,Chen WJ,Liu PH,Hsu KL,Hwang JJ,Lai LP,Lin JL,Tseng CD,Tseng YZ

    更新日期:2004-04-13 00:00:00

  • Transcriptome profiling and network analysis of genetically hypertensive mice identifies potential pharmacological targets of hypertension.

    abstract::Hypertension is a condition with major cardiovascular and renal complications, affecting nearly a billion patients worldwide. Few validated gene targets are available for pharmacological intervention, so there is a need to identify new biological pathways regulating blood pressure and containing novel targets for trea...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00010.2010

    authors: Puig O,Wang IM,Cheng P,Zhou P,Roy S,Cully D,Peters M,Benita Y,Thompson J,Cai TQ

    更新日期:2010-09-01 00:00:00

  • Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion.

    abstract::The gastric entero-chromaffin-like (ECL) cell plays a key regulatory role in peripheral regulation of acid secretion due to the release of histamine that stimulates acid secretion by the parietal cell. Studies in intact animals, gastric glands, and isolated cells after short-term culture have shown expression of stimu...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00271.2005

    authors: Lambrecht NW,Yakubov I,Zer C,Sachs G

    更新日期:2006-03-13 00:00:00

  • Use of contiguous congenic strains in analyzing compound QTLs.

    abstract::Genetic analysis of polygenic traits in rats and mice has been very useful for finding the approximate chromosomal locations of the genes causing quantitative phenotypic variation, so-called quantitative trait loci (QTL). Further localization of the causative genes and their ultimate identification has, however, prove...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00136.2011

    authors: Rapp JP,Joe B

    更新日期:2012-02-01 00:00:00

  • Functional genomics of the dopaminergic system in hypertension.

    abstract::Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. Under normal conditions, D(1)-like receptors (D(1) and D(5)) inhibit sodium transport in the kidney and intestine. However, in the Dahl salt-sensitive and spontaneou...

    journal_title:Physiological genomics

    pub_type: 杂志文章,评审

    doi:10.1152/physiolgenomics.00127.2004

    authors: Zeng C,Sanada H,Watanabe H,Eisner GM,Felder RA,Jose PA

    更新日期:2004-11-17 00:00:00

  • Vertical selection for nuclear and mitochondrial genomes shapes gut microbiota and modifies risks for complex diseases.

    abstract::Here we postulate that the heritability of complex disease traits previously ascribed solely to the inheritance of the nuclear and mitochondrial genomes is broadened to encompass a third component of the holobiome, the microbiome. To test this, we expanded on the selectively bred low capacity runner/high capacity runn...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00089.2019

    authors: Zhang Y,Kumarasamy S,Mell B,Cheng X,Morgan EE,Britton SL,Vijay-Kumar M,Koch LG,Joe B

    更新日期:2020-01-01 00:00:00

  • In silico structure-function analysis of pathological variation in the HSD11B2 gene sequence.

    abstract::11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) is a short-chain dehydrogenase/reductase (SDR) responsible for inactivating cortisol and preventing its binding to the mineralocorticoid receptor (MR). Nonfunctional mutations in HSD11B2, the gene encoding 11betaHSD2, cause the hypertensive syndrome of apparent m...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00053.2010

    authors: Manning JR,Bailey MA,Soares DC,Dunbar DR,Mullins JJ

    更新日期:2010-08-01 00:00:00

  • Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse.

    abstract::In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, the pathogenic destruction of the insulin-producing pancreatic beta-cells is under the control of and influenced by distinct subsets of T lymphocytes. To identify the critical genes expressed by autoimmune T cells, antigen presenting cells, and pan...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00173.2004

    authors: Vukkadapu SS,Belli JM,Ishii K,Jegga AG,Hutton JJ,Aronow BJ,Katz JD

    更新日期:2005-04-14 00:00:00

  • Identification of new targets of Drosophila pre-mRNA adenosine deaminase.

    abstract::Adenosine deaminase acting on RNA (ADAR) in Drosophila and mammals has recently become the target of numerous investigations. It is now clear that this protein has a number of functions in the nervous system. Indeed, the mutation of ADAR in Drosophila (dADAR) results in many pathological and physiological changes, suc...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00093.2003

    authors: Xia S,Yang J,Su Y,Qian J,Ma E,Haddad GG

    更新日期:2005-01-20 00:00:00

  • Quantitative trait locus on chromosome 20q13 for plasma levels of C-reactive protein in healthy whites: the HERITAGE Family Study.

    abstract::C-reactive protein (CRP) is a sensitive marker of systemic low-grade inflammation. Increased plasma levels of CRP predict the risk of cardiovascular and metabolic diseases. Although genetic factors account for 30-40% of individual differences in plasma CRP levels, genomic regions contributing to CRP levels remain unkn...

    journal_title:Physiological genomics

    pub_type: 杂志文章,多中心研究

    doi:10.1152/physiolgenomics.00054.2005

    authors: Lakka TA,Rankinen T,Rice T,Leon AS,Rao DC,Skinner JS,Bouchard C

    更新日期:2006-10-11 00:00:00

  • A physiogenomic approach to study the regulation of blood pressure.

    abstract::Several vasoregulatory systems including the renin-angiotensin system, sympathetic vasoregulation, and cytokine release have been studied extensively. The aim of the present study was to establish a physiogenomic screening model for differentially expressed genes in the regulation of blood pressure that might give a h...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00077.2005

    authors: Westhoff TH,Scheid S,Tölle M,Kaynak B,Schmidt S,Zidek W,Sperling S,van der Giet M

    更新日期:2005-09-21 00:00:00

  • Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles.

    abstract::Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00210.2004

    authors: Kostrominova TY,Dow DE,Dennis RG,Miller RA,Faulkner JA

    更新日期:2005-07-14 00:00:00

  • Long human CHGA flanking chromosome 14 sequence required for optimal BAC transgenic "rescue" of disease phenotypes in the mouse Chga knockout.

    abstract::Chromogranin A (CHGA) plays a catalytic role in formation of catecholamine storage vesicles and also serves as precursor to the peptide fragment catestatin, a catecholamine secretory inhibitor whose expression is diminished in the hypertensive individuals. We previously reported the hypertensive, hyperadrenergic pheno...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00086.2009

    authors: Vaingankar SM,Li Y,Corti A,Biswas N,Gayen J,O'Connor DT,Mahata SK

    更新日期:2010-03-03 00:00:00

  • Transcriptional reprogramming and ultrastructure during atrophy and recovery of mouse soleus muscle.

    abstract::This study investigated the use of the hindlimb suspension (HS) and reloading model of mice for the mapping of ultrastructural and gene expressional alterations underlying load-dependent muscular adaptations. Mice were hindlimb suspended for 7 days or kept as controls (n = 12). Soleus muscles were harvested after HS (...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00100.2004

    authors: Däpp C,Schmutz S,Hoppeler H,Flück M

    更新日期:2004-12-15 00:00:00

  • Resequencing of IRS2 reveals rare variants for obesity but not fasting glucose homeostasis in Hispanic children.

    abstract::Our objective was to resequence insulin receptor substrate 2 (IRS2) to identify variants associated with obesity- and diabetes-related traits in Hispanic children. Exonic and intronic segments, 5' and 3' flanking regions of IRS2 (∼14.5 kb), were bidirectionally sequenced for single nucleotide polymorphism (SNP) discov...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00019.2011

    authors: Butte NF,Voruganti VS,Cole SA,Haack K,Comuzzie AG,Muzny DM,Wheeler DA,Chang K,Hawes A,Gibbs RA

    更新日期:2011-09-22 00:00:00

  • Patterns of gene expression in the sheep heart during the perinatal period revealed by transcriptomic modeling.

    abstract::Septa from sheep hearts at 130 days gestation, term, and 14-day-old lambs were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. We used Bioconductor for R to model five major patterns of coexpressed genes. Gene ontology and transcription factor anal...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00027.2015

    authors: Richards EM,Rabaglino MB,Antolic A,Wood CE,Keller-Wood M

    更新日期:2015-09-01 00:00:00

  • Both isoforms of ketohexokinase are dispensable for normal growth and development.

    abstract::Dietary fructose intake has dramatically increased over recent decades and is implicated in the high rates of obesity, hypertension, and type 2 diabetes (metabolic syndrome) in Western societies. The molecular determinants of this epidemiologic correlation are incompletely defined, but high-flux fructose catabolism in...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00128.2010

    authors: Diggle CP,Shires M,McRae C,Crellin D,Fisher J,Carr IM,Markham AF,Hayward BE,Asipu A,Bonthron DT

    更新日期:2010-11-29 00:00:00