PMC:5118429 / 36702-42845 JSONTXT

{"project":"2_test","denotations":[{"id":"27920797-21525308-33226493","span":{"begin":1734,"end":1738},"obj":"21525308"},{"id":"27920797-23967015-33226494","span":{"begin":2002,"end":2006},"obj":"23967015"},{"id":"27920797-21525308-33226495","span":{"begin":2161,"end":2165},"obj":"21525308"},{"id":"27920797-16904174-33226496","span":{"begin":2530,"end":2534},"obj":"16904174"},{"id":"27920797-25126380-33226497","span":{"begin":2551,"end":2555},"obj":"25126380"},{"id":"27920797-24503509-33226498","span":{"begin":2656,"end":2660},"obj":"24503509"},{"id":"27920797-16330774-33226499","span":{"begin":2793,"end":2797},"obj":"16330774"},{"id":"27920797-23788712-33226500","span":{"begin":2814,"end":2818},"obj":"23788712"},{"id":"27920797-22872758-33226501","span":{"begin":2916,"end":2920},"obj":"22872758"},{"id":"27920797-22209759-33226502","span":{"begin":2938,"end":2942},"obj":"22209759"},{"id":"27920797-25186009-33226503","span":{"begin":3124,"end":3128},"obj":"25186009"},{"id":"27920797-22196728-33226504","span":{"begin":3340,"end":3344},"obj":"22196728"},{"id":"27920797-16330774-33226505","span":{"begin":3484,"end":3488},"obj":"16330774"},{"id":"27920797-15968590-33226506","span":{"begin":3653,"end":3657},"obj":"15968590"},{"id":"27920797-19648401-33226507","span":{"begin":3793,"end":3797},"obj":"19648401"},{"id":"27920797-23555284-33226508","span":{"begin":3966,"end":3970},"obj":"23555284"},{"id":"27920797-12932319-33226509","span":{"begin":4140,"end":4144},"obj":"12932319"},{"id":"27920797-21902831-33226510","span":{"begin":4320,"end":4324},"obj":"21902831"},{"id":"27920797-22539751-33226511","span":{"begin":4566,"end":4570},"obj":"22539751"},{"id":"27920797-24491505-33226512","span":{"begin":4765,"end":4769},"obj":"24491505"},{"id":"27920797-12559913-33226513","span":{"begin":5092,"end":5096},"obj":"12559913"},{"id":"27920797-11319218-33226514","span":{"begin":5169,"end":5173},"obj":"11319218"},{"id":"27920797-11517927-33226515","span":{"begin":5195,"end":5199},"obj":"11517927"},{"id":"27920797-10845425-33226516","span":{"begin":5252,"end":5256},"obj":"10845425"},{"id":"27920797-10749891-33226517","span":{"begin":5274,"end":5278},"obj":"10749891"},{"id":"27920797-9299163-33226518","span":{"begin":5327,"end":5331},"obj":"9299163"},{"id":"27920797-9407041-33226519","span":{"begin":5354,"end":5358},"obj":"9407041"},{"id":"27920797-9566966-33226520","span":{"begin":5375,"end":5379},"obj":"9566966"},{"id":"27920797-11023827-33226521","span":{"begin":5413,"end":5417},"obj":"11023827"},{"id":"27920797-14720518-33226522","span":{"begin":5677,"end":5681},"obj":"14720518"},{"id":"27920797-15621511-33226523","span":{"begin":5743,"end":5747},"obj":"15621511"},{"id":"27920797-21525308-33226524","span":{"begin":5766,"end":5770},"obj":"21525308"},{"id":"27920797-25880457-33226525","span":{"begin":5789,"end":5793},"obj":"25880457"},{"id":"27920797-1610937-33226526","span":{"begin":6107,"end":6111},"obj":"1610937"},{"id":"27920797-16891212-33226527","span":{"begin":6137,"end":6141},"obj":"16891212"}],"text":"Putative genes\nNetworks of genes offer insight to the molecular relationships among genes. The network was visualized considering genes and neighboring genes located in the same genome scaffold as the SNPs we identified in the wssGWAS in 20-SNP windows responsible for ~1.0% or more of the total genetic variance for the analyzed traits. Genes included in the network are described in Tables S2–S6. The network includes 115 gene nodes, of which 21 nodes were genes detected by the wssGWAS analysis (green nodes) while the rest were connecting neighbors (pink nodes, Figure 6). In this network, SRY (sex determining region Y)-box 2 (Sox2), Kinase suppressor of ras 1 (Ksr1), Tripartite motif-containing 33 (Trim33), and Nitric oxide synthase 2 inducible (Nos2) were well-connected gene nodes linking to 29, 11, 7, and 6 other gene nodes, respectively.\nFigure 6 Network of genes and neighboring genes in the same scaffold as the SNPs identified in the wssGWAS in windows responsible for ~1.0% or more of the total genetic variance of the analyzed traits. Green nodes denote genes and near genes detected by the wssGWAS analysis and pink nodes denote connecting neighbors. Edges denote known relationships between genes in the SysBiomics repository. Framed genes (red square) are discussed in the manuscript. A number of genes detected by wssGWAS analysis within windows responsible for 1.0% or greater of the trait variance have been identified in mammalian systems as significant for muscle development, particularly with respect to the maintenance of hyperplastic capacity. Rainbow trout exhibit indeterminate growth potential as they have the ability increase both body length and muscle mass throughout adulthood (Johnston et al., 2011). A physiological mechanism unique to indeterminate growers is the ability to maintain a population of myogenic precursor cells with proliferative capacity that then differentiate into myotubes or contribute to nuclear accretion (Mommsen, 2001; Froehlich et al., 2013). Therefore, the continued ability for hyperplasia and hypertrophy in skeletal muscle contributes to the indeterminate growth phenotype (Johnston et al., 2011). In this regard, SNPs affecting genes related to myogenic and cell proliferation mechanisms are expected to affect growth and fillet yield.\nOne gene detected by wssGWAS analysis that was the most connected node was Sox2. The Sox2 gene plays a critical role in maintenance and proliferation of pluripotent and neural progenitor stem cells (Takahashi and Yamanaka, 2006; Zhang and Cui, 2014) through its interaction with transforming Growth Factor β (TGFb) signaling (Gaarenstroom and Hill, 2014), although little is known about the role of Sox2 in muscle. Albeit, TGFb ligands like myostatin inhibit muscle growth (Lee et al., 2005; Phelps et al., 2013), partially through reductions in myogenic precursor cell proliferation (Garikipati and Rodgers, 2012; Seiliez et al., 2012). Trim33 is another gene detected by wssGWAS analysis that is up-regulated during muscle regeneration in mice and appears to play a role in myoblast proliferation (Mohassel et al., 2015). Therefore, similar to Sox2, Trim33 may also contribute to maintaining a proliferating population of myogenic precursor cells throughout development in the rainbow trout. Trim33 also inhibits Smad4 (Xi et al., 2011), a transcription factor activated by TGFb signaling that inhibits muscle regeneration and maintenance of myogenesis with age (Lee et al., 2005).\nA third gene identified by wssGWAS analysis was Fragile X mental retardation gene 1 (Fxr1), an autosomal gene that is highly expressed in muscle (Blonden et al., 2005). Depletion of this gene during early development of the zebrafish leads to cardiomyopathy and muscular dystrophy (Van't Padje et al., 2009). In cultured muscle cells, depletion of Fxr1 reduced myoblast abundance, suggesting an evolutionarily-conserved role for Fxr1 protein in myogenesis (Davidovic et al., 2013). A fourth gene detected by wssGWAS analysis that may affect myogenic capacity was Ksr1. This gene is a scaffold protein for the Raf/MEK/ERK kinase cascade (Ory et al., 2003). Although, a role of for Ksr1 in muscle has not been demonstrated, activation of the Raf/Mek/ERK kinase cascade promotes proliferation of myogenic cells (Knight and Kothary, 2011). A final gene that may affect myogenesis was Proviral integration site 1 (Pim1), a gene that, when overexpressed in cardiomyocytes, causes increases in regenerative capacity and increases the pool of progenitor cells (Del Re and Sadoshima, 2012), although it is unknown if this gene has significance in skeletal muscle. However, expression of Pim1 has been positively correlated with intramuscular fat content in steers (Sadkowski et al., 2014).\nAnother pair of genes that were detected by wssGWAS and are known to encode proteins with functional importance to muscle physiology are the cysteine proteases Calpain-1 (Capn1) and Calpain-2 (Capn2). Calpains are calcium activated cysteine proteases regulated by myogenic factors like myoD and myogenin (Dedieu et al., 2003). Calpains have a relevant role in signal transduction (Glading et al., 2001; Sato and Kawashima, 2001), cell-cycle regulation, apoptosis (Atencio et al., 2000; Patel and Lane, 2000), cell spreading and migration (Dourdin et al., 1997; Huttenlocher et al., 1997; Potter et al., 1998), and myogenesis (Barnoy et al., 2000). Calpains are also involved with myofibrillar protein disassembly and degradation, contributing to loss of the Z disk (Busch et al., 1972). Increased calpain activity in muscle occurs during periods of muscle reorganization and restructuring (Dedieu et al., 2004), such as during weight loss and rapid growth (Salem et al., 2005; Johnston et al., 2011; Salmerón et al., 2015), therefore it is feasible that SNPs affecting calpain-related proteolysis contributes to differences in muscle growth capacity. Calpain-induced protein degradation is also associated with post-mortem proteolysis so genetic variation in the calpain system may result in differences in fillet quality (Koohmaraie, 1992; Delbarre-Ladrat et al., 2006)."}

{"project":"MyTest","denotations":[{"id":"27920797-21525308-33226493","span":{"begin":1734,"end":1738},"obj":"21525308"},{"id":"27920797-23967015-33226494","span":{"begin":2002,"end":2006},"obj":"23967015"},{"id":"27920797-21525308-33226495","span":{"begin":2161,"end":2165},"obj":"21525308"},{"id":"27920797-16904174-33226496","span":{"begin":2530,"end":2534},"obj":"16904174"},{"id":"27920797-25126380-33226497","span":{"begin":2551,"end":2555},"obj":"25126380"},{"id":"27920797-24503509-33226498","span":{"begin":2656,"end":2660},"obj":"24503509"},{"id":"27920797-16330774-33226499","span":{"begin":2793,"end":2797},"obj":"16330774"},{"id":"27920797-23788712-33226500","span":{"begin":2814,"end":2818},"obj":"23788712"},{"id":"27920797-22872758-33226501","span":{"begin":2916,"end":2920},"obj":"22872758"},{"id":"27920797-22209759-33226502","span":{"begin":2938,"end":2942},"obj":"22209759"},{"id":"27920797-25186009-33226503","span":{"begin":3124,"end":3128},"obj":"25186009"},{"id":"27920797-22196728-33226504","span":{"begin":3340,"end":3344},"obj":"22196728"},{"id":"27920797-16330774-33226505","span":{"begin":3484,"end":3488},"obj":"16330774"},{"id":"27920797-15968590-33226506","span":{"begin":3653,"end":3657},"obj":"15968590"},{"id":"27920797-19648401-33226507","span":{"begin":3793,"end":3797},"obj":"19648401"},{"id":"27920797-23555284-33226508","span":{"begin":3966,"end":3970},"obj":"23555284"},{"id":"27920797-12932319-33226509","span":{"begin":4140,"end":4144},"obj":"12932319"},{"id":"27920797-21902831-33226510","span":{"begin":4320,"end":4324},"obj":"21902831"},{"id":"27920797-22539751-33226511","span":{"begin":4566,"end":4570},"obj":"22539751"},{"id":"27920797-24491505-33226512","span":{"begin":4765,"end":4769},"obj":"24491505"},{"id":"27920797-12559913-33226513","span":{"begin":5092,"end":5096},"obj":"12559913"},{"id":"27920797-11319218-33226514","span":{"begin":5169,"end":5173},"obj":"11319218"},{"id":"27920797-11517927-33226515","span":{"begin":5195,"end":5199},"obj":"11517927"},{"id":"27920797-10845425-33226516","span":{"begin":5252,"end":5256},"obj":"10845425"},{"id":"27920797-10749891-33226517","span":{"begin":5274,"end":5278},"obj":"10749891"},{"id":"27920797-9299163-33226518","span":{"begin":5327,"end":5331},"obj":"9299163"},{"id":"27920797-9407041-33226519","span":{"begin":5354,"end":5358},"obj":"9407041"},{"id":"27920797-9566966-33226520","span":{"begin":5375,"end":5379},"obj":"9566966"},{"id":"27920797-11023827-33226521","span":{"begin":5413,"end":5417},"obj":"11023827"},{"id":"27920797-14720518-33226522","span":{"begin":5677,"end":5681},"obj":"14720518"},{"id":"27920797-15621511-33226523","span":{"begin":5743,"end":5747},"obj":"15621511"},{"id":"27920797-21525308-33226524","span":{"begin":5766,"end":5770},"obj":"21525308"},{"id":"27920797-25880457-33226525","span":{"begin":5789,"end":5793},"obj":"25880457"},{"id":"27920797-1610937-33226526","span":{"begin":6107,"end":6111},"obj":"1610937"},{"id":"27920797-16891212-33226527","span":{"begin":6137,"end":6141},"obj":"16891212"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Putative genes\nNetworks of genes offer insight to the molecular relationships among genes. The network was visualized considering genes and neighboring genes located in the same genome scaffold as the SNPs we identified in the wssGWAS in 20-SNP windows responsible for ~1.0% or more of the total genetic variance for the analyzed traits. Genes included in the network are described in Tables S2–S6. The network includes 115 gene nodes, of which 21 nodes were genes detected by the wssGWAS analysis (green nodes) while the rest were connecting neighbors (pink nodes, Figure 6). In this network, SRY (sex determining region Y)-box 2 (Sox2), Kinase suppressor of ras 1 (Ksr1), Tripartite motif-containing 33 (Trim33), and Nitric oxide synthase 2 inducible (Nos2) were well-connected gene nodes linking to 29, 11, 7, and 6 other gene nodes, respectively.\nFigure 6 Network of genes and neighboring genes in the same scaffold as the SNPs identified in the wssGWAS in windows responsible for ~1.0% or more of the total genetic variance of the analyzed traits. Green nodes denote genes and near genes detected by the wssGWAS analysis and pink nodes denote connecting neighbors. Edges denote known relationships between genes in the SysBiomics repository. Framed genes (red square) are discussed in the manuscript. A number of genes detected by wssGWAS analysis within windows responsible for 1.0% or greater of the trait variance have been identified in mammalian systems as significant for muscle development, particularly with respect to the maintenance of hyperplastic capacity. Rainbow trout exhibit indeterminate growth potential as they have the ability increase both body length and muscle mass throughout adulthood (Johnston et al., 2011). A physiological mechanism unique to indeterminate growers is the ability to maintain a population of myogenic precursor cells with proliferative capacity that then differentiate into myotubes or contribute to nuclear accretion (Mommsen, 2001; Froehlich et al., 2013). Therefore, the continued ability for hyperplasia and hypertrophy in skeletal muscle contributes to the indeterminate growth phenotype (Johnston et al., 2011). In this regard, SNPs affecting genes related to myogenic and cell proliferation mechanisms are expected to affect growth and fillet yield.\nOne gene detected by wssGWAS analysis that was the most connected node was Sox2. The Sox2 gene plays a critical role in maintenance and proliferation of pluripotent and neural progenitor stem cells (Takahashi and Yamanaka, 2006; Zhang and Cui, 2014) through its interaction with transforming Growth Factor β (TGFb) signaling (Gaarenstroom and Hill, 2014), although little is known about the role of Sox2 in muscle. Albeit, TGFb ligands like myostatin inhibit muscle growth (Lee et al., 2005; Phelps et al., 2013), partially through reductions in myogenic precursor cell proliferation (Garikipati and Rodgers, 2012; Seiliez et al., 2012). Trim33 is another gene detected by wssGWAS analysis that is up-regulated during muscle regeneration in mice and appears to play a role in myoblast proliferation (Mohassel et al., 2015). Therefore, similar to Sox2, Trim33 may also contribute to maintaining a proliferating population of myogenic precursor cells throughout development in the rainbow trout. Trim33 also inhibits Smad4 (Xi et al., 2011), a transcription factor activated by TGFb signaling that inhibits muscle regeneration and maintenance of myogenesis with age (Lee et al., 2005).\nA third gene identified by wssGWAS analysis was Fragile X mental retardation gene 1 (Fxr1), an autosomal gene that is highly expressed in muscle (Blonden et al., 2005). Depletion of this gene during early development of the zebrafish leads to cardiomyopathy and muscular dystrophy (Van't Padje et al., 2009). In cultured muscle cells, depletion of Fxr1 reduced myoblast abundance, suggesting an evolutionarily-conserved role for Fxr1 protein in myogenesis (Davidovic et al., 2013). A fourth gene detected by wssGWAS analysis that may affect myogenic capacity was Ksr1. This gene is a scaffold protein for the Raf/MEK/ERK kinase cascade (Ory et al., 2003). Although, a role of for Ksr1 in muscle has not been demonstrated, activation of the Raf/Mek/ERK kinase cascade promotes proliferation of myogenic cells (Knight and Kothary, 2011). A final gene that may affect myogenesis was Proviral integration site 1 (Pim1), a gene that, when overexpressed in cardiomyocytes, causes increases in regenerative capacity and increases the pool of progenitor cells (Del Re and Sadoshima, 2012), although it is unknown if this gene has significance in skeletal muscle. However, expression of Pim1 has been positively correlated with intramuscular fat content in steers (Sadkowski et al., 2014).\nAnother pair of genes that were detected by wssGWAS and are known to encode proteins with functional importance to muscle physiology are the cysteine proteases Calpain-1 (Capn1) and Calpain-2 (Capn2). Calpains are calcium activated cysteine proteases regulated by myogenic factors like myoD and myogenin (Dedieu et al., 2003). Calpains have a relevant role in signal transduction (Glading et al., 2001; Sato and Kawashima, 2001), cell-cycle regulation, apoptosis (Atencio et al., 2000; Patel and Lane, 2000), cell spreading and migration (Dourdin et al., 1997; Huttenlocher et al., 1997; Potter et al., 1998), and myogenesis (Barnoy et al., 2000). Calpains are also involved with myofibrillar protein disassembly and degradation, contributing to loss of the Z disk (Busch et al., 1972). Increased calpain activity in muscle occurs during periods of muscle reorganization and restructuring (Dedieu et al., 2004), such as during weight loss and rapid growth (Salem et al., 2005; Johnston et al., 2011; Salmerón et al., 2015), therefore it is feasible that SNPs affecting calpain-related proteolysis contributes to differences in muscle growth capacity. Calpain-induced protein degradation is also associated with post-mortem proteolysis so genetic variation in the calpain system may result in differences in fillet quality (Koohmaraie, 1992; Delbarre-Ladrat et al., 2006)."}