K C Chang

University of Glasgow, Glasgow, Scotland, United Kingdom

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Publications (18)36.75 Total impact

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    ABSTRACT: Ten genes (ANK1, bR10D1, CA3, EPOR, HMGA2, MYPN, NME1, PDGFRA, ERC1, TTN), whose candidacy for meat-quality and carcass traits arises from their differential expression in prenatal muscle development, were examined for association in 1700 performance-tested fattening pigs of commercial purebred and crossbred herds of Duroc, Pietrain, Pietrain x (Landrace x Large White), Duroc x (Landrace x Large White) as well as in an experimental F(2) population based on a reciprocal cross of Duroc and Pietrain. Comparative sequencing revealed polymorphic sites segregating across commercial breeds. Genetic mapping results corresponded to pre-existing assignments to porcine chromosomes or current human-porcine comparative maps. Nine of these genes showed association with meat-quality and carcass traits at a nominal P-value of < or = 0.05; PDGFRA revealed no association reaching the P < or = 0.05 threshold. In particular, HMGA2, CA3, EPOR, NME1 and TTN were associated with meat colour, pH and conductivity of loin 24 h postmortem; CA3 and MYPN exhibited association with ham weight and lean content (FOM) respectively at P-values of < 0.003 that correspond to false discovery rates of < 0.05. However, none of the genes showed significant associations for a particular trait across all populations. The study revealed statistical-genetic evidence for association of the functional candidate genes with traits related to meat quality and muscle deposition. The polymorphisms detected are not likely causal, but markers were identified that are in linkage disequilibrium with causal genetic variation within particular populations.
    No preview · Article · Oct 2007 · Animal Genetics
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    ABSTRACT: In skeletal muscle, calcineurin is crucial for myocyte differentiation and in the determination of the slow oxidative fibre phenotype, both processes being important determinants of muscle performance, metabolic health and meat-animal production. Fibre type is defined by the isoform identity of the skeletal myosin heavy chain (MyHC). We have examined the responses of the major MyHC genes to calcineurin signalling during fibre formation of muscle C2C12 cells. We have found that calcineurin acts as a signal to up-regulate the fast-oxidative MyHC2a gene and to down-regulate the faster MyHC2x and MyHC2b genes in a manner that appears to be NFAT-independent. Contrary to expectation, the up-regulation of MyHCslow by calcineurin seems to be time-dependent and is only detectable once the initial differential expression of the post-natal fast MyHC genes has been established. The simultaneous elevated expression of MyHC2a and the repression of MyHC2x and MyHC2b expression indicate that both processes (elevation and repression) are actively coordinated during oxidative fibre conversion. We have further determined that muscle LIM protein (MLP), a calcineurin-binding Z-line co-factor, is induced by calcineurin and that its co-expression with calcineurin has an additive effect on MyHCslow expression. Hence, post-natal fast MyHCs are important early effector targets of calcineurin, whereas MyHCslow up-regulation is mediated in part by calcineurin-induced MLP.
    No preview · Article · Oct 2007 · Cell and Tissue Research
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    K.C. Chang
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    ABSTRACT: The molecular basis and control of the biochemical and biophysical properties of skeletal muscle, regarded as muscle phenotype, are examined in terms of fibre number, fibre size and fibre types. A host of external factors or stimuli, such as ligand binding and contractile activity, are transduced in muscle into signalling pathways that lead to protein modifications and changes in gene expression which ultimately result in the establishment of the specified phenotype. In skeletal muscle, the key signalling cascades include the Ras-extracellular signal regulated kinase-mitogen activated protein kinase (Erk-MAPK), the phosphatidylinositol 3'-kinase (PI3K)-Akt1, p38 MAPK, and calcineurin pathways. The molecular effects of external factors on these pathways revealed complex interactions and functional overlap. A major challenge in the manipulation of muscle of farm animals lies in the identification of regulatory and target genes that could effect defined and desirable changes in muscle quality and quantity. To this end, recent advances in functional genomics that involve the use of micro-array technology and proteomics are increasingly breaking new ground in furthering our understanding of the molecular determinants of muscle phenotype.
    Preview · Article · Jun 2007 · animal
  • JD Meissner · KC Chang · HP Kubis · AR Nebreda · G Gros · RJ Scheibe

    No preview · Article · Jan 2006

  • No preview · Article · Jan 2005
  • N da Costa · C McGillivray · QF Bai · J.D. Wood · G Evans · K.-C. Chang
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    ABSTRACT: Little is known about the molecular changes in response to dietary restriction (energy and/or protein) in young growing skeletal muscles. To profile such changes and to gain insights into the signaling molecules that could mediate the diet effects, a dedicated porcine skeletal muscle cDNA-microarray approach was used to characterize differential muscle gene expression between conventionally fed and diet-restricted (20% less protein and 7% less energy) growing pigs, reared from 9 to 21 wk of age. In both red and white muscles, diet restriction resulted in the accumulation of significantly more intramuscular fat, and in the increased expression of genes involved in substrate (protein, glycogen, and lipid) turnover, in translation and mitochondrial function, and in raising glycolytic and oxidative phosphorylation potentials. The unexpected increase in intramuscular lipids in diet-restricted growing pigs could have important health implications for restricted diets in childhood. Despite reduced circulating insulin, more genes, including several novel growth modulatory genes, had higher expression levels, indicating that the cellular response to dietary restriction is an active process. One such responsive gene, P311, was most highly expressed in striated muscles and had a differentiation-dependent increase of expression in murine C2C12 cells, suggesting a role in differentiation/postdifferentiation phenotype determination.
    No preview · Article · Oct 2004 · Journal of Nutrition
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    ABSTRACT: A study in 192 entire male pigs examined the effects of breed, diet and muscle on growth, fatness, sensory traits and fatty acid composition. There were four breeds: two modern breeds, Duroc and Large White and two traditional breeds, Berkshire and Tamworth. The diets differed in energy:protein ratio, being conventional (C) and low protein (LP) diets, respectively. Muscles investigated were the `white' longissimus dorsi (LD) and the `red' psoas major (PS). Breed influenced growth rate and fatness, the modern breeds being faster-growing with leaner carcasses. However, the concentrations of neutral lipid fatty acids and marbling fat (neutral lipid+phosopholipid fatty acids) were higher in Berkshire and Duroc, in both LD and PS. Relationships between marbling fat and P2 fat thickness showed clear breed effects, with Duroc having high marbling fat at low P2 and Tamworth low marbling fat at high P2. Breed effects on sensory scores given by the trained taste panel to griddled LD and PS steaks were relatively small. Breed affected the fatty acid composition of intramuscular neutral lipid, with high % values for the saturated fatty acids, 14:0 and 16:0 in Berkshire and Tamworth (fat carcasses) and high values for polyunsaturated fatty acids in Duroc and Large White (lean carcasses). Duroc had particularly high concentrations of the long-chain polyunsaturated fatty acids, 20:5n-3 and 22:6n-3 in phospholipid of both muscles. Diet influenced growth rate and fatness, the LP diet slowing growth and producing fatter meat, more so in the two modern breeds, and particularly in intramuscular rather than subcutaneous fat. This diet produced more tender and juicy meat, although pork flavour and flavour liking were reduced. The PS muscle had higher tenderness, juiciness, pork flavour, flavour liking and overall liking scores than LD. The concentration of phospholipid fatty acids was higher in PS than LD but neutral lipid fatty acid content and marbling fat were higher in LD.
    Full-text · Article · Aug 2004 · Meat Science

  • No preview · Article · Jan 2004
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    ABSTRACT: Porcine skeletal muscle fibres were molecularly classified, using in situ hybridisation and immunocytochemistry, into four types, according to the isoform of myosin heavy chain (MyHC) that was present in each fibre (MyHC slow/I, MyHC 2a, MyHC 2x and MyHC 2b). The relationship between MyHC fibre types and meat quality traits between two phenotypically divergent muscles [longissimus dorsi (LD) and psoas], and between the same muscles of different breeds (traditional Berkshire and Tamworth, and modern Duroc-based and Large White-based) were examined. We found that the greater abundance of fast oxidative-glycolytic MyHC 2a and 2x fibres in the psoas was associated with superior meat quality traits, and that the greater presence of fast glycolytic MyHC 2b fibres in the LD could account for less favourable quality traits, both in terms of pH, drip loss, grain, colour, yield force and work done. Although significant correlations were found between specific fibre types and quality traits, within either the psoas or LD muscle of some breeds, no consistent correlation was found across both muscles and all breeds. This finding was in line with the view that a given fibre type could have considerable differences in phenotype between breeds, and between muscles. The observed inverse compositional and functional-meat quality relationship between MyHC 2b and 2x fibres, and MyHC 2b and 2a fibres could form a basis of fibre type manipulation to improve meat quality.
    No preview · Article · May 2003 · Meat Science
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    ABSTRACT: Microarray profiling has the potential to illuminate the molecular processes that govern the phenotypic characteristics of porcine skeletal muscles, such as hypertrophy or atrophy, and the expression of specific fibre types. This information is not only important for understanding basic muscle biology but also provides underpinning knowledge for enhancing the efficiency of livestock production. We report on the de novo development of a composite skeletal muscle cDNA microarray, comprising 5500 clones from two developmentally distinct cDNA libraries (longissimus dorsi of a 50-day porcine foetus and the gastrocnemius of a 3-day-old pig). Clones selected for the microarray assembly were of low to moderate abundance, as indicated by colony hybridisation. We profiled the differential expression of genes between the psoas (red muscle) and the longissimus dorsi (white muscle), by co-hybridisation of Cy3 and Cy5 labelled cDNA derived from these two muscles. Results from seven microarray slides (replicates) correctly identified genes that were expected to be differentially expressed, as well as a number of novel candidate regulatory genes. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray. We have developed a porcine skeletal muscle cDNA microarray and have identified a number of candidate genes that could be involved in muscle phenotype determination, including several members of the casein kinase 2 signalling pathway.
    Full-text · Article · Apr 2003 · BMC Genomics
  • K C Chang · N D Beuzen · A.D Hall
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    ABSTRACT: We investigated the presence of dinucleotide repeats (microsatellites) in a porcine skeletal muscle cDNA library. In total, microsatellites were found in nearly 4% of all muscle cDNA clones, of which CT- and TG-repeats were the most prevalent. We found a near full-length desmin cDNA clone with a CT-repeat sited downstream from its stop codon. From 44 commercially reared pigs, six allelic length polymorphisms were identified at this microsatellite locus (128, 131, 134, 135, 136, and 138 bp), whose desmin genotypes were associated with pH change after slaughter (P=0.031) and colour variation of meat (P<0.001 for hue, P<0.005 for lightness, and P=0.014 for b colour). Two of the genotypes (131/131 bp and 131/135 bp) were consistent with paler meat. This finding indicates the usefulness of the cDNA library approach to generate markers for marker-assisted selection and suggests that the desmin microsatellite could be a possible selection marker.
    No preview · Article · Mar 2003 · The Veterinary Journal
  • YM Sun · N da Costa · KC Chang
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    ABSTRACT: Members of the myosin heavy chain (MyHC) gene family are subjected to temporal regulation of gene switching during development. One strategy to the identification of cis-acting regulatory elements that are involved in temporal or fibre-type specific regulation is to undertake a comparative analysis of the MyHC gene family between the pig, an important target species, and other mammals, like human whose entire genome has been recently sequenced. Towards this end, we report here on the isolation, and characterisation of the porcine cardiac (MyHC slow/beta and alpha) and skeletal MyHC (embryonic, 2a, 2x, 2b and perinatal) gene clusters, and their structural comparisons with mouse and human clusters. The genome organisation of both clusters in the pig, human and mouse is conserved as having the same gene order, similar intergenic distances, and in the same head-to-tail orientation. For a period of pre-natal muscle growth, relative expression of MyHC isoforms, as determined by TaqMan real-time RT-PCR, correlated with the gene order in the skeletal MyHC cluster (embryonic > 2a > 2x > 2b) suggesting the possible presence of DNA elements on the same side as the MyHC embryonic gene that direct temporal regulation.
    No preview · Article · Feb 2003 · Journal of Muscle Research and Cell Motility
  • H Alzuherri · KC Chang

    No preview · Article · Jan 2003 · Cellular Signalling
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    ABSTRACT: Postnatal skeletal muscle fiber type is commonly defined by one of four major myosin heavy chain (MyHC) gene isoforms (slow/I, 2a, 2x, and 2b) that are expressed. We report on the novel use of combined TaqMan quantitative real-time RT-PCR and image analysis of serial porcine muscle sections, subjected to in situ hybridization (ISH) and immunocytochemistry (IHC), to quantify the mRNA expression of each MyHC isoform within its corresponding fiber type, termed relative fiber type-restricted expression. This versatile approach will allow quantitative temporospatial comparisons of each MyHC isoform among muscles from the same or different individuals. Using this approach on porcine skeletal muscles, we found that the relative fiber type-restricted expression of each postnatal MyHC gene showed wide spatial and temporal variation within a given muscle and between muscles. Marked differences were also observed among pig breeds. Notably, of the four postnatal MyHC isoforms, the 2a MyHC gene showed the highest relative fiber type-restricted expression in each muscle examined, regardless of age, breed, or muscle type. This suggests that although 2a fibers are a minor fiber type, they may be disproportionately more important as a determinant of overall muscle function than was previously believed.
    Preview · Article · Apr 2002 · Journal of Histochemistry and Cytochemistry
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    ABSTRACT: The porcine embryonic myosin heavy chain (MyHC) is a major isoform in foetal skeletal muscle, and is the last remaining major porcine skeletal MyHC gene to be isolated and characterised. We report here on its cDNA and genomic isolation, molecular characterisation, quantification and expression. Unlike all other porcine and mammalian skeletal MyHC genes reported to date, the deduced translated start site of the porcine embryonic gene was located in exon 2, instead of exon 3. Its promoter conferred differentiation-specific expression. We found, by quantitative real-time RT-PCR, that for much of gestation the embryonic MyHC was by far the most transcriptionally active gene compared with the slow/I and perinatal MyHC isoforms, and it was consistently more highly expressed than the perinatal isoform throughout gestation. The embryonic MyHC isoform was, however, rapidly down-regulated at around birth. By contrast, 22 weeks after birth, the porcine perinatal isoform remained detectable by PCR. Additionally, we discovered the presence of differential splicing at the 3'-end of the embryonic MyHC gene that resulted in an in-frame deletion, with the consequential loss of 93 amino acids close to the ACD domain, a region that is important for the assembly of myosin filaments. The detection of this truncated variant points to a possible major post-transcriptional mechanism of embryonic MyHC regulation that may be linked to myosin filament formation or turnover.
    No preview · Article · Feb 2001 · Journal of Muscle Research and Cell Motility
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    N D Beuzen · M J Stear · K C Chang
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    ABSTRACT: The use of DNA markers to define the genetic makeup (genotype) and predict the performance of an animal is a powerful aid to animal breeding. One strategy is known as marker-assisted selection (MAS). MAS facilitates the exploitation of existing genetic diversity in breeding populations and can be used to improve a whole range of desirable traits. DNA markers are, by definition, polymorphic, and the methods used to define DNA markers include restriction fragment length polymorphisms (RFLPs), microsatellites, and single nucleotide polymorphisms (SNPs). Linkage analysis, association analysis and analysis of gene function can be used to determine which polymorphisms are useful markers for desirable traits. Future prospects include the use of high throughput DNA microarray (DNA chip) technology which could revolutionize animal breeding in the next millennium.
    Full-text · Article · Aug 2000 · The Veterinary Journal
  • K C Chang
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    ABSTRACT: The porcine sarcomeric fast 2a myosin heavy chain (MyHC) gene was previously found to require a region extending 3' from the transcriptional start site for high levels of expression. Here we established the existence of two novel opposing regulatory domains in intron 2. A positive regulatory element, defined to a 75bp region, resembles a TATA-less intronic promoter, with a consensus transcription initiation element. It can up-regulate its endogenous or a heterologous muscle promoter in a position specific manner, and on its own drive a reporter gene. In tandem with it is a dominant negative regulatory element, localised to a 81bp region, which can down-regulate its native gene and a heterologous muscle promoter. Bandshift and DNase I footprinting assays demonstrated that specific nuclear factors bound to both regulatory elements are distinctly different. Both elements appear to have no counterpart in intron 2 of the porcine fast 2x and 2b MyHC genes. Taken together, we demonstrate for the first time that a 5'-end terminal intron of a sarcomeric MyHC gene contains two critical regulatory domains, which may be involved in the complexity of temporo-spatial expression.
    No preview · Article · Feb 2000 · Journal of Muscle Research and Cell Motility

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