PMC:5118444 / 1355-5084
Annnotations
2_test
{"project":"2_test","denotations":[{"id":"27920798-21293372-33484628","span":{"begin":149,"end":153},"obj":"21293372"},{"id":"27920798-18923514-33484629","span":{"begin":278,"end":282},"obj":"18923514"},{"id":"27920798-21956041-33484630","span":{"begin":300,"end":304},"obj":"21956041"},{"id":"27920798-23375656-33484631","span":{"begin":324,"end":328},"obj":"23375656"},{"id":"27920798-21846351-33484632","span":{"begin":430,"end":434},"obj":"21846351"},{"id":"27920798-22138850-33484633","span":{"begin":454,"end":458},"obj":"22138850"},{"id":"27920798-22916802-33484634","span":{"begin":477,"end":481},"obj":"22916802"},{"id":"27920798-21111040-33484635","span":{"begin":509,"end":513},"obj":"21111040"},{"id":"27920798-23565757-33484636","span":{"begin":527,"end":531},"obj":"23565757"},{"id":"27920798-19079605-33484637","span":{"begin":555,"end":559},"obj":"19079605"},{"id":"27920798-20969757-33484638","span":{"begin":583,"end":587},"obj":"20969757"},{"id":"27920798-23270433-33484639","span":{"begin":602,"end":606},"obj":"23270433"},{"id":"27920798-23829399-33484640","span":{"begin":623,"end":627},"obj":"23829399"},{"id":"27920798-25896665-33484641","span":{"begin":629,"end":633},"obj":"25896665"},{"id":"27920798-23763846-33484642","span":{"begin":664,"end":668},"obj":"23763846"},{"id":"27920798-25378104-33484643","span":{"begin":681,"end":685},"obj":"25378104"},{"id":"27920798-21083884-33484644","span":{"begin":716,"end":720},"obj":"21083884"},{"id":"27920798-19521496-33484645","span":{"begin":833,"end":837},"obj":"19521496"},{"id":"27920798-8875890-33484646","span":{"begin":904,"end":908},"obj":"8875890"},{"id":"27920798-18493018-33484647","span":{"begin":927,"end":931},"obj":"18493018"},{"id":"27920798-18817307-33484648","span":{"begin":1119,"end":1123},"obj":"18817307"},{"id":"27920798-20212021-33484649","span":{"begin":1125,"end":1129},"obj":"20212021"},{"id":"27920798-20459598-33484650","span":{"begin":1147,"end":1151},"obj":"20459598"},{"id":"27920798-25917301-33484652","span":{"begin":1216,"end":1220},"obj":"25917301"},{"id":"27920798-27578198-33484653","span":{"begin":1238,"end":1242},"obj":"27578198"},{"id":"27920798-27005566-33484654","span":{"begin":1277,"end":1281},"obj":"27005566"},{"id":"27920798-19390634-33484655","span":{"begin":1339,"end":1343},"obj":"19390634"},{"id":"27920798-20377913-33484656","span":{"begin":1357,"end":1361},"obj":"20377913"},{"id":"27920798-21345189-33484657","span":{"begin":1375,"end":1379},"obj":"21345189"},{"id":"27920798-23144949-33484659","span":{"begin":1402,"end":1406},"obj":"23144949"},{"id":"27920798-27209136-33484660","span":{"begin":1448,"end":1452},"obj":"27209136"},{"id":"27920798-22085807-33484661","span":{"begin":1510,"end":1514},"obj":"22085807"},{"id":"27920798-22082336-33484662","span":{"begin":1529,"end":1533},"obj":"22082336"},{"id":"27920798-22300768-33484663","span":{"begin":1552,"end":1556},"obj":"22300768"},{"id":"27920798-23543395-33484664","span":{"begin":1571,"end":1575},"obj":"23543395"},{"id":"27920798-27775157-33484665","span":{"begin":1590,"end":1594},"obj":"27775157"},{"id":"27920798-27209136-33484666","span":{"begin":1614,"end":1618},"obj":"27209136"},{"id":"27920798-15273396-33484667","span":{"begin":2186,"end":2190},"obj":"15273396"},{"id":"27920798-24303503-33484668","span":{"begin":2784,"end":2788},"obj":"24303503"},{"id":"27920798-19915526-33484669","span":{"begin":2945,"end":2949},"obj":"19915526"}],"text":"Introduction\nCopy number variations (CNVs) are gains and losses of large regions of genomic sequence between individuals of a species (Mills et al., 2011). CNVs have been well-studied and linked to various phenotypic traits and diseases in humans and rodents (Cook and Scherer, 2008; Almal and Padh, 2012; Girirajan et al., 2013). Initial CNV studies have been performed in a number of domesticated animals: dog (Nicholas et al., 2011; Alvarez and Akey, 2012; Berglund et al., 2012), sheep (Fontanesi et al., 2011; Liu et al., 2013), pig (Fadista et al., 2008; Ramayo-Caldas et al., 2010; Chen et al., 2012; Paudel et al., 2013, 2015), chicken (Crooijmans et al., 2013; Yi et al., 2014), and goat (Fontanesi et al., 2010). These studies have linked many phenotypic traits to CNV, including chicken pea-comb phenotype (Wright et al., 2009) and white coat color in pigs and sheep (Johansson Moller et al., 1996; Norris and Whan, 2008).\nSeveral studies have investigated CNV in the bovine genome. Cattle CNVs have been reported using a variety of platforms, including comparative genomic hybridization arrays (Liu et al., 2008, 2010; Fadista et al., 2010), the Illumina BovineHD BeadChip (Hou et al., 2012a; Wu et al., 2015; Aguilar et al., 2016; Prinsen et al., 2016; Xu et al., 2016), the Illumina BovineSNP50 BeadChip (Matukumalli et al., 2009; Bae et al., 2010; Hou et al., 2011, 2012b; Jiang et al., 2012; Bagnato et al., 2015; Ben Sassi et al., 2016), and next-generation sequencing (NGS) (Stothard et al., 2011; Zhan et al., 2011; Bickhart et al., 2012; Choi et al., 2013; Keel et al., 2016; Ben Sassi et al., 2016). In these studies, it is reported that copy number variable regions comprise ~2–7% of the cattle genome.\nIn cattle, as well as many other species, relatively little is known about the properties and dynamics of CNVs. Open questions remain about the frequency of CNVs in the genome, sizes, and locations, and chromosomal properties. In addition, the extent to which CNV affect phenotype is not well understood. In humans, it has been observed that two unrelated, healthy individuals can differ from one another in gene copy number across their genomes (Sabat et al., 2004), which raises uncertainty about the existence of a characteristic number of copies of any one gene. Of all of the topics related to CNVs, our knowledge of the functional and evolutionary impact of CNVs is the most limited.\nWhole genome sequence (WGS) is often used in CNV discovery. However, until sequencing costs drop dramatically, it is simply not feasible to generate the high coverage (\u003e 10x) whole genome sequence, suggested for CNV detection, on large numbers of animals. Due to its cost-effectiveness, WES is routinely used for the detection of coding sequence variation (Guo et al., 2013). In humans, the exome comprises approximately 1–3% of the genome, but accounts for over 85% of all mutations identified in Mendelian disorders (Ng et al., 2010), making it a desirable and practical approach for investigating variations in coding sequence.\nIn this study, we investigated some evolutionary and functional aspects of coding sequence copy number variation in the bovine genome. We first characterized CNV regions detected in whole exome sequence from 175 influential sires used in the USMARC Germplasm Evaluation project and identified genes overlapping with CNVRs. We then examined selective constraint on CNV genes to test the hypothesis that genes affected by CNV are subject to accelerated sequence evolution compared to copy number neutral genes. In addition, we utilized gene expression data and protein-protein interaction networks to investigate network centrality and tissue-specific expression patterns of CNV genes."}
MyTest
{"project":"MyTest","denotations":[{"id":"27920798-21293372-33484628","span":{"begin":149,"end":153},"obj":"21293372"},{"id":"27920798-18923514-33484629","span":{"begin":278,"end":282},"obj":"18923514"},{"id":"27920798-21956041-33484630","span":{"begin":300,"end":304},"obj":"21956041"},{"id":"27920798-23375656-33484631","span":{"begin":324,"end":328},"obj":"23375656"},{"id":"27920798-21846351-33484632","span":{"begin":430,"end":434},"obj":"21846351"},{"id":"27920798-22138850-33484633","span":{"begin":454,"end":458},"obj":"22138850"},{"id":"27920798-22916802-33484634","span":{"begin":477,"end":481},"obj":"22916802"},{"id":"27920798-21111040-33484635","span":{"begin":509,"end":513},"obj":"21111040"},{"id":"27920798-23565757-33484636","span":{"begin":527,"end":531},"obj":"23565757"},{"id":"27920798-19079605-33484637","span":{"begin":555,"end":559},"obj":"19079605"},{"id":"27920798-20969757-33484638","span":{"begin":583,"end":587},"obj":"20969757"},{"id":"27920798-23270433-33484639","span":{"begin":602,"end":606},"obj":"23270433"},{"id":"27920798-23829399-33484640","span":{"begin":623,"end":627},"obj":"23829399"},{"id":"27920798-25896665-33484641","span":{"begin":629,"end":633},"obj":"25896665"},{"id":"27920798-23763846-33484642","span":{"begin":664,"end":668},"obj":"23763846"},{"id":"27920798-25378104-33484643","span":{"begin":681,"end":685},"obj":"25378104"},{"id":"27920798-21083884-33484644","span":{"begin":716,"end":720},"obj":"21083884"},{"id":"27920798-19521496-33484645","span":{"begin":833,"end":837},"obj":"19521496"},{"id":"27920798-8875890-33484646","span":{"begin":904,"end":908},"obj":"8875890"},{"id":"27920798-18493018-33484647","span":{"begin":927,"end":931},"obj":"18493018"},{"id":"27920798-18817307-33484648","span":{"begin":1119,"end":1123},"obj":"18817307"},{"id":"27920798-20212021-33484649","span":{"begin":1125,"end":1129},"obj":"20212021"},{"id":"27920798-20459598-33484650","span":{"begin":1147,"end":1151},"obj":"20459598"},{"id":"27920798-25917301-33484652","span":{"begin":1216,"end":1220},"obj":"25917301"},{"id":"27920798-27578198-33484653","span":{"begin":1238,"end":1242},"obj":"27578198"},{"id":"27920798-27005566-33484654","span":{"begin":1277,"end":1281},"obj":"27005566"},{"id":"27920798-19390634-33484655","span":{"begin":1339,"end":1343},"obj":"19390634"},{"id":"27920798-20377913-33484656","span":{"begin":1357,"end":1361},"obj":"20377913"},{"id":"27920798-21345189-33484657","span":{"begin":1375,"end":1379},"obj":"21345189"},{"id":"27920798-23144949-33484659","span":{"begin":1402,"end":1406},"obj":"23144949"},{"id":"27920798-27209136-33484660","span":{"begin":1448,"end":1452},"obj":"27209136"},{"id":"27920798-22085807-33484661","span":{"begin":1510,"end":1514},"obj":"22085807"},{"id":"27920798-22082336-33484662","span":{"begin":1529,"end":1533},"obj":"22082336"},{"id":"27920798-22300768-33484663","span":{"begin":1552,"end":1556},"obj":"22300768"},{"id":"27920798-23543395-33484664","span":{"begin":1571,"end":1575},"obj":"23543395"},{"id":"27920798-27775157-33484665","span":{"begin":1590,"end":1594},"obj":"27775157"},{"id":"27920798-27209136-33484666","span":{"begin":1614,"end":1618},"obj":"27209136"},{"id":"27920798-15273396-33484667","span":{"begin":2186,"end":2190},"obj":"15273396"},{"id":"27920798-24303503-33484668","span":{"begin":2784,"end":2788},"obj":"24303503"},{"id":"27920798-19915526-33484669","span":{"begin":2945,"end":2949},"obj":"19915526"}],"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":"Introduction\nCopy number variations (CNVs) are gains and losses of large regions of genomic sequence between individuals of a species (Mills et al., 2011). CNVs have been well-studied and linked to various phenotypic traits and diseases in humans and rodents (Cook and Scherer, 2008; Almal and Padh, 2012; Girirajan et al., 2013). Initial CNV studies have been performed in a number of domesticated animals: dog (Nicholas et al., 2011; Alvarez and Akey, 2012; Berglund et al., 2012), sheep (Fontanesi et al., 2011; Liu et al., 2013), pig (Fadista et al., 2008; Ramayo-Caldas et al., 2010; Chen et al., 2012; Paudel et al., 2013, 2015), chicken (Crooijmans et al., 2013; Yi et al., 2014), and goat (Fontanesi et al., 2010). These studies have linked many phenotypic traits to CNV, including chicken pea-comb phenotype (Wright et al., 2009) and white coat color in pigs and sheep (Johansson Moller et al., 1996; Norris and Whan, 2008).\nSeveral studies have investigated CNV in the bovine genome. Cattle CNVs have been reported using a variety of platforms, including comparative genomic hybridization arrays (Liu et al., 2008, 2010; Fadista et al., 2010), the Illumina BovineHD BeadChip (Hou et al., 2012a; Wu et al., 2015; Aguilar et al., 2016; Prinsen et al., 2016; Xu et al., 2016), the Illumina BovineSNP50 BeadChip (Matukumalli et al., 2009; Bae et al., 2010; Hou et al., 2011, 2012b; Jiang et al., 2012; Bagnato et al., 2015; Ben Sassi et al., 2016), and next-generation sequencing (NGS) (Stothard et al., 2011; Zhan et al., 2011; Bickhart et al., 2012; Choi et al., 2013; Keel et al., 2016; Ben Sassi et al., 2016). In these studies, it is reported that copy number variable regions comprise ~2–7% of the cattle genome.\nIn cattle, as well as many other species, relatively little is known about the properties and dynamics of CNVs. Open questions remain about the frequency of CNVs in the genome, sizes, and locations, and chromosomal properties. In addition, the extent to which CNV affect phenotype is not well understood. In humans, it has been observed that two unrelated, healthy individuals can differ from one another in gene copy number across their genomes (Sabat et al., 2004), which raises uncertainty about the existence of a characteristic number of copies of any one gene. Of all of the topics related to CNVs, our knowledge of the functional and evolutionary impact of CNVs is the most limited.\nWhole genome sequence (WGS) is often used in CNV discovery. However, until sequencing costs drop dramatically, it is simply not feasible to generate the high coverage (\u003e 10x) whole genome sequence, suggested for CNV detection, on large numbers of animals. Due to its cost-effectiveness, WES is routinely used for the detection of coding sequence variation (Guo et al., 2013). In humans, the exome comprises approximately 1–3% of the genome, but accounts for over 85% of all mutations identified in Mendelian disorders (Ng et al., 2010), making it a desirable and practical approach for investigating variations in coding sequence.\nIn this study, we investigated some evolutionary and functional aspects of coding sequence copy number variation in the bovine genome. We first characterized CNV regions detected in whole exome sequence from 175 influential sires used in the USMARC Germplasm Evaluation project and identified genes overlapping with CNVRs. We then examined selective constraint on CNV genes to test the hypothesis that genes affected by CNV are subject to accelerated sequence evolution compared to copy number neutral genes. In addition, we utilized gene expression data and protein-protein interaction networks to investigate network centrality and tissue-specific expression patterns of CNV genes."}