FTO基因多态性与黔北麻羊血清脂代谢指标的关联性研究
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摘要
脂肪肥胖相关基因(fat mass and obesity associated gene, FTO)是通过全基因组扫描技术发现的肥胖易感基因。FTO通过转录因子及转运蛋白调节脂肪酸转运和脂肪代谢相关基因的表达,参与脂肪组织的发育、维持及沉积。黔北麻羊(Capra hircus)是贵州省三大地方品种之一,产肉性能良好,肉质鲜美。本研究以黔北麻羊为研究对象,探究FTO基因外显子多态性与脂代谢相关的血清生理生化指标的关联性。首先采用混合DNA池结合PCR直接测序技术筛选SNPs,然后单个样本直接测序确定突变位点的基因型,运用SPSS 17.0对FTO基因各突变位点不同基因型与血清瘦素、激素敏感脂肪酶(hormone-sensitive lipase, HSL)、脂联素、总胆固醇、甘油三脂、高密度脂蛋白、低密度脂蛋白、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase, AST)进行分析。结果显示,在受试群体中共发现9个SNPs,分别为:g.C10943T、g.G109518T、g.T125300A、g.C125357T、g.G125405T、gT125417C、g.T426229C、g.C426244G和g.G426347A,其中g.G109518T和g.G426347A位点突变分别位于第二和第九内含子区域。卡方分析显示,各突变位点都属于中度多态性(0.5黔北麻羊脂质代谢具有一定的相关性,为筛选山羊脂肪沉积及肉质调控的辅助选择标记提供了理论参考。
Fat mass and obesity associated gene(FTO) is an obesity susceptibility gene discovered by genome-wide scanning technology. FTO could regulate fatty acid transport and fat metabolism-related genes by transcription factors and transporters, participating in the development, maintenance and deposition of adipose tissue. Qianbei Ma goat is one of the three local varieties in Guizhou province. It is delicious and has good meat production. In present study, Qianbei Ma sheep(Capra hircus) was taken as the investigated subject, and the association between FTO gene exon polymorphism and serum physiological and biochemical indexes related to lipid metabolism was studied. SNPs were firstly screened by hybrid DNA pool combined with PCR direct sequencing technology. The genotypes of the mutation sites were directly sequenced by single sample. The different genotypes of FTO gene mutations and serum leptin, hormone sensitive lipase(HSL),adiponectin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, alanine aminotransferase(ALT), aspartate aminotransferase(AST) were determined by SPSS 17.0. A total of 9 SNPs were found in the tested goat population: g.C10943 T, g.G109518 T, g.T125300 A, g.C125357 T, g.G125405 T,gT125417 C, g. T426229 C, g. C426244 G, g. G426347 A, where g. G109518 T and g. G426347 A site mutations were located in the second and ninth intron regions, respectively. Chi-square results showed that each mutation site belonged to moderate polymorphism(0.5
Fat mass and obesity associated gene(FTO) is an obesity susceptibility gene discovered by genome-wide scanning technology. FTO could regulate fatty acid transport and fat metabolism-related genes by transcription factors and transporters, participating in the development, maintenance and deposition of adipose tissue. Qianbei Ma goat is one of the three local varieties in Guizhou province. It is delicious and has good meat production. In present study, Qianbei Ma sheep(Capra hircus) was taken as the investigated subject, and the association between FTO gene exon polymorphism and serum physiological and biochemical indexes related to lipid metabolism was studied. SNPs were firstly screened by hybrid DNA pool combined with PCR direct sequencing technology. The genotypes of the mutation sites were directly sequenced by single sample. The different genotypes of FTO gene mutations and serum leptin, hormone sensitive lipase(HSL),adiponectin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, alanine aminotransferase(ALT), aspartate aminotransferase(AST) were determined by SPSS 17.0. A total of 9 SNPs were found in the tested goat population: g.C10943 T, g.G109518 T, g.T125300 A, g.C125357 T, g.G125405 T,gT125417 C, g. T426229 C, g. C426244 G, g. G426347 A, where g. G109518 T and g. G426347 A site mutations were located in the second and ninth intron regions, respectively. Chi-square results showed that each mutation site belonged to moderate polymorphism(0.5
引文
付言峰,李兰,王学敏,等.2013.苏钟猪FTO基因的mRNA表达、克隆测序及其生物信息学分析[J].华北农学报,28(1):128-134.(Fu Y F,Li L,Wang X M,et al.2013.mRNA expression Suzhong porcine FTO gene,cloned and sequenced and bioinformatics analysis[J].North China Agricultural Sciences,28(1):128-134.)
桂林生,昝林森,王洪宝,等.2015.SIRT1和SIRT2基因多态性及合并基因型与秦川牛肉用性状的关联分析[J].畜牧兽医学报,46(10):1741-1749.(Gui L S,Yan L S,Wang H B,et al.2015.Association analysis between SIRT1 and SIRT2 gene polymorphisms and combined genotypes and traits of Qinchuan beef[J].Journal of Animal Husbandry and Veterinary Medicine,46(10):1741-1749.)
黄英,杨明华,毕保良,等.2014.乌金猪FTO基因的克隆和表达分析[J].生物技术通讯,25(3):316-322.(Huang Y,Yang M H,Bi B L,et al.2014.Cloning and expression analysis of FTO gene in Wujin pig[J].Biotechnology Communication,25(3):316-322.)
林亚秋,廖红海,贺庆华,等.2016.山羊FTO基因克隆及其表达谱[J].畜牧兽医学报,47(5):888-898.(Lin Y Q,Liao H H,He Q H,et al.2016.Cloning and expression profiling of goat FTO gene[J].Journal of Animal Husbandry and Veterinary Medicine,47(5):888-898.)
王玉峰.2009.鸡FTO基因:组织特异性表达、中枢核团定位、品种差异以及禁食的影响[D].硕士学位论文,南京农业大学,导师:赵茹茜,pp.9-20.(Wang Y F.2009.Chicken FTO gene:Tissue-specific expression,central nucleus localization,variety differences and effects of fasting[D].Thesis for M.S.,Nanjing Agricultural University,Supervisor:Zhao R Z,pp.9-20.)
翁吉梅,罗铮,徐伟,等.2018.黔北麻羊FTO基因多态性及生物信息学分析[J].中国畜牧杂志,54(9):60-64.(Weng J M,Luo Z,Xu W,et al.2018.Polymorphism and bioinformatics analysis of FTO gene in Qianbei Ma sheep[J].Chinese Journal of Animal Science,54(9):60-64.)
吴森,桂林生,昝林森,等.2018.南阳牛ATP5B基因启动子区域多态性与生长性状的关联性研究[J].农业生物技术学报,26(9):1535-1545.(Wu S,Gui L S,Zan L S,et al.2018.Correlation between polymorphisms of ATP5Bgene promoter and growth traits in Nanyang cattle[J].Journal of Agricultural Biotechnology,26(9):1535-1545.)
张莹,吴铁梅,王雪,等.2016.脂肪与肥胖相关基因对动物脂肪代谢的调节[J].动物营养学报,28(4):999-1003.(Zhang Y,Wu T M,Wang X,et al.2016.Regulation of fat and obesity-related genes on fat metabolism in animals[J].Journal of Animal Nutrition,28(4):999-1003.)
赵宪林,曹少杰,王俊全,等.2018.MC4R基因多态性及基因型组合与藏羊生长性状的关联分析[J].农业生物技术学报,26(3):429-436.(Zhao X L,Cao S J,Wang J Q,et al.2018.Correlation analysis of polymorphism and genotype combination of MC4R gene and growth traits of Tibetan sheep[J].Journal of Agricultural Biotechnology,26(3):429-436.)
朱琳娜.2014.FTO、METTL3基因表达对猪脂肪细胞m RNA N6-甲基腺苷水平及脂肪沉积的影响研究[D].浙江大学,硕士学位论文,导师:汪以真,pp:11-34.(Zhu L N.2014.Effects of FTO and METTL3 gene expression on N6-methyladenosine levels and fat deposition in porcine fat cells[D].Thesis for M.S.,Zhejiang University,Suppervisor:Wang Y Z,pp:11-34.)
Amélie B,Etienne L,Emmanuelle M,et al.2011.FTO is increased in muscle during type 2 diabetes,and its overexpression in myotubes alters insulin signaling,enhances lipogenesis and ROS production,and induces mitochondrial dysfunction[J].Diabetes,60(1):258-268.
Bravard A,Vial G,Chauvin M A,et al.2014.FTO contributes to hepatic metabolism regulation through regulation of leptin action and STAT3 signalling in liver[J].Cell Communication&Signaling,12(1):2-13.
Chen H,Pan Y X,Dudenhausen E E,et al.2004.Amino acid deprivation induces the transcription rate of the human asparagine synthetase gene through a timed program of expression and promoter binding of nutrient-responsive basic region/leucine zipper transcription factors as well as localized histone acetylation[J].Journal of Biological Chemistry,279(49):50829-50839.
Cheung M K,Gulati P,O'Rahilly S,et al.2013.FTO expression is regulated by availability of essential amino acids[J].International Journal of Obesity,37(5):744-747.
Falnes P?,Johansen R F,Seeberg E.2002.AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli[J].Nature,419(6903):178-182.
Frayling T M,Timpson N J,Weedon M N,et al.2007.A common variant in the FTO gene is associated with Body Mass Index and predisposes to childhood and adult obesity[J].Science,316(5826):889-894.
Khella M S,Hamdy N M,Amin A I,et al.2017.The(FTO)gene polymorphism is associated with metabolic syndrome risk in Egyptian females:A case-control study[J].BMC Medical Genetics,18(1):101-108.
Mcmurray F,Church C D,Larder R,et al.2013.Adult onset global loss of the Fto gene alters body composition and metabolism in the mouse[J].PLoS Genetics,9(1):e1003166.
Mo C,Yang M,Han X,et al.2017.Fat mass and obesity-associated protein attenuates lipid accumulation in macrophage foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice[J].Journal of Hypertension,35(4):810-821.
Palii S S,Kays C E,Deval C,et al.2009.Specificity of amino acid regulated gene expression:Analysis of genes subjected to either complete or single amino acid deprivation[J].Amino Acids,37(1):79-88.
Pawan G,Yeo G S H.2013.The biology of FTO:From nucleic acid demethylase to amino acid sensor[J].Diabetologia,56(10):2113-2121.
Roffeei S N,Mohamed Z,Reynolds G P,et al.2014.Association of FTO,LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics[J].Pharmacogenomics,15(4):477-485.
Sonestedt E,Gullberg B,Ericson U,et al.2011.Association between fat intake,physical activity and mortality depending on genetic variation in FTO[J].International Journal of Obesity,35(8):1041-1049.
Speakman J R.2010.FTO effect on energy demand versus food intake[J].Nature,458(7289):894-898.
Trewick S C,HenshawT F,Hausinger R P,et al.2002.Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage[J].Nature,419(6903):174-178.
W?hlén K,Sj?lin E,Hoffstedt J.2008.The common rs9939609 gene variant of the fat mass-and obesity-associated gene FTO is related to fat cell lipolysis[J].Journal of Lipid Research,49(3):607-611.
Zabena C,González-Sánchez J L,Martínez-Larrad M T,et al.2009.The FTO obesity gene.Genotyping and gene expression analysis in morbidly obese patients[J].Obesity Surgery,19(1):87-95.
桂林生,昝林森,王洪宝,等.2015.SIRT1和SIRT2基因多态性及合并基因型与秦川牛肉用性状的关联分析[J].畜牧兽医学报,46(10):1741-1749.(Gui L S,Yan L S,Wang H B,et al.2015.Association analysis between SIRT1 and SIRT2 gene polymorphisms and combined genotypes and traits of Qinchuan beef[J].Journal of Animal Husbandry and Veterinary Medicine,46(10):1741-1749.)
黄英,杨明华,毕保良,等.2014.乌金猪FTO基因的克隆和表达分析[J].生物技术通讯,25(3):316-322.(Huang Y,Yang M H,Bi B L,et al.2014.Cloning and expression analysis of FTO gene in Wujin pig[J].Biotechnology Communication,25(3):316-322.)
林亚秋,廖红海,贺庆华,等.2016.山羊FTO基因克隆及其表达谱[J].畜牧兽医学报,47(5):888-898.(Lin Y Q,Liao H H,He Q H,et al.2016.Cloning and expression profiling of goat FTO gene[J].Journal of Animal Husbandry and Veterinary Medicine,47(5):888-898.)
王玉峰.2009.鸡FTO基因:组织特异性表达、中枢核团定位、品种差异以及禁食的影响[D].硕士学位论文,南京农业大学,导师:赵茹茜,pp.9-20.(Wang Y F.2009.Chicken FTO gene:Tissue-specific expression,central nucleus localization,variety differences and effects of fasting[D].Thesis for M.S.,Nanjing Agricultural University,Supervisor:Zhao R Z,pp.9-20.)
翁吉梅,罗铮,徐伟,等.2018.黔北麻羊FTO基因多态性及生物信息学分析[J].中国畜牧杂志,54(9):60-64.(Weng J M,Luo Z,Xu W,et al.2018.Polymorphism and bioinformatics analysis of FTO gene in Qianbei Ma sheep[J].Chinese Journal of Animal Science,54(9):60-64.)
吴森,桂林生,昝林森,等.2018.南阳牛ATP5B基因启动子区域多态性与生长性状的关联性研究[J].农业生物技术学报,26(9):1535-1545.(Wu S,Gui L S,Zan L S,et al.2018.Correlation between polymorphisms of ATP5Bgene promoter and growth traits in Nanyang cattle[J].Journal of Agricultural Biotechnology,26(9):1535-1545.)
张莹,吴铁梅,王雪,等.2016.脂肪与肥胖相关基因对动物脂肪代谢的调节[J].动物营养学报,28(4):999-1003.(Zhang Y,Wu T M,Wang X,et al.2016.Regulation of fat and obesity-related genes on fat metabolism in animals[J].Journal of Animal Nutrition,28(4):999-1003.)
赵宪林,曹少杰,王俊全,等.2018.MC4R基因多态性及基因型组合与藏羊生长性状的关联分析[J].农业生物技术学报,26(3):429-436.(Zhao X L,Cao S J,Wang J Q,et al.2018.Correlation analysis of polymorphism and genotype combination of MC4R gene and growth traits of Tibetan sheep[J].Journal of Agricultural Biotechnology,26(3):429-436.)
朱琳娜.2014.FTO、METTL3基因表达对猪脂肪细胞m RNA N6-甲基腺苷水平及脂肪沉积的影响研究[D].浙江大学,硕士学位论文,导师:汪以真,pp:11-34.(Zhu L N.2014.Effects of FTO and METTL3 gene expression on N6-methyladenosine levels and fat deposition in porcine fat cells[D].Thesis for M.S.,Zhejiang University,Suppervisor:Wang Y Z,pp:11-34.)
Amélie B,Etienne L,Emmanuelle M,et al.2011.FTO is increased in muscle during type 2 diabetes,and its overexpression in myotubes alters insulin signaling,enhances lipogenesis and ROS production,and induces mitochondrial dysfunction[J].Diabetes,60(1):258-268.
Bravard A,Vial G,Chauvin M A,et al.2014.FTO contributes to hepatic metabolism regulation through regulation of leptin action and STAT3 signalling in liver[J].Cell Communication&Signaling,12(1):2-13.
Chen H,Pan Y X,Dudenhausen E E,et al.2004.Amino acid deprivation induces the transcription rate of the human asparagine synthetase gene through a timed program of expression and promoter binding of nutrient-responsive basic region/leucine zipper transcription factors as well as localized histone acetylation[J].Journal of Biological Chemistry,279(49):50829-50839.
Cheung M K,Gulati P,O'Rahilly S,et al.2013.FTO expression is regulated by availability of essential amino acids[J].International Journal of Obesity,37(5):744-747.
Falnes P?,Johansen R F,Seeberg E.2002.AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli[J].Nature,419(6903):178-182.
Frayling T M,Timpson N J,Weedon M N,et al.2007.A common variant in the FTO gene is associated with Body Mass Index and predisposes to childhood and adult obesity[J].Science,316(5826):889-894.
Khella M S,Hamdy N M,Amin A I,et al.2017.The(FTO)gene polymorphism is associated with metabolic syndrome risk in Egyptian females:A case-control study[J].BMC Medical Genetics,18(1):101-108.
Mcmurray F,Church C D,Larder R,et al.2013.Adult onset global loss of the Fto gene alters body composition and metabolism in the mouse[J].PLoS Genetics,9(1):e1003166.
Mo C,Yang M,Han X,et al.2017.Fat mass and obesity-associated protein attenuates lipid accumulation in macrophage foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice[J].Journal of Hypertension,35(4):810-821.
Palii S S,Kays C E,Deval C,et al.2009.Specificity of amino acid regulated gene expression:Analysis of genes subjected to either complete or single amino acid deprivation[J].Amino Acids,37(1):79-88.
Pawan G,Yeo G S H.2013.The biology of FTO:From nucleic acid demethylase to amino acid sensor[J].Diabetologia,56(10):2113-2121.
Roffeei S N,Mohamed Z,Reynolds G P,et al.2014.Association of FTO,LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics[J].Pharmacogenomics,15(4):477-485.
Sonestedt E,Gullberg B,Ericson U,et al.2011.Association between fat intake,physical activity and mortality depending on genetic variation in FTO[J].International Journal of Obesity,35(8):1041-1049.
Speakman J R.2010.FTO effect on energy demand versus food intake[J].Nature,458(7289):894-898.
Trewick S C,HenshawT F,Hausinger R P,et al.2002.Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage[J].Nature,419(6903):174-178.
W?hlén K,Sj?lin E,Hoffstedt J.2008.The common rs9939609 gene variant of the fat mass-and obesity-associated gene FTO is related to fat cell lipolysis[J].Journal of Lipid Research,49(3):607-611.
Zabena C,González-Sánchez J L,Martínez-Larrad M T,et al.2009.The FTO obesity gene.Genotyping and gene expression analysis in morbidly obese patients[J].Obesity Surgery,19(1):87-95.
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