德州驴NCAPG-DCAF16基因区域多态性与生长性状的关联分析
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摘要
旨在探讨NCAPG-DCAF16基因区域在德州驴群体中的遗传多态性以及与生长性状的关联性,进而得到显著相关的遗传标记,为德州驴的分子标记辅助选择提供理论基础。本研究采用DNA混池测序技术对NCAPG-DCAF16基因区域的多态性进行检测;基于DNA混池测序结果,运用质谱分型技术对227头德州驴群体中的SNPs位点进行基因型检测,分析基因型与初生、3月龄、6月龄3个时期相关生长性状的关联性。结果表明:1)通过DNA混池测序发现,NCAPG基因上的SNPs位点包括第9内含子上rs1(T>C),第11内含子上rs2(A>G),第19内含子上rs4(C>G),第8内含子上rs5(C>G);DCAF16基因第2外显子发现一个同义突变,即位点rs008(A>G)。2)初生时期的关联分析显示,rs1位点基因型CC个体的平均尻长显著高于CT型个体(P<0.05);3月龄时期各基因型的表型平均值无显著差异(P>0.05);在6月龄阶段,基因型为TT个体的平均胸宽与CC个体相比差异极显著(P<0.01),TT和CT基因型个体的平均管围均显著高于CC个体(P<0.05)。3)rs4位点的关联分析揭示了GG基因型个体在初生时期的平均胸深显著高于GC基因型(P<0.05),3月龄时期各基因型之间的平均表型值无显著差异(P>0.05);CC基因型个体6月龄时期的平均胸宽和管围显著高于GG基因型(P<0.05)。4)rs008位点关联分析结果表明,各基因型之间初生时期的表型值无显著差异(P>0.05);AA、GA基因型个体3月龄时期的体重、体高和尻高都显著高于GG基因型(P<0.05);AA、GA基因型个体6月龄时期的体高和胸围都极显著高于GG基因型个体(P<0.01),GA基因型与GG基因型个体间的胸深、尻高的差异达到极显著水平(P<0.01),GA基因型个体的尻宽显著高于GG和AA基因型(P<0.05)。5)根据连锁不平衡分析结果,rs1、rs2、rs4和rs5的组合基因型在德州驴群体中有5种。关联分析结果揭示了TTAACCCC组合基因型个体6月龄时期的平均胸宽显著高于CCGGGGGG组合基因型(P<0.05)。综上,德州驴群体中NCAPG-DCAF16基因区域5个SNPs位点对生长性状均有显著影响,特别是rs008位点与德州驴体重、体高等重要生长性状极显著相关,可用于德州驴的分子标记辅助选择,提高德州驴育种效率。
The study aimed to investigate the genetic polymorphisms of NCAPG-DCAF16 region in Dezhou donkeys and their associations with growth traits,which can help to mine significant genetic markers for molecular marker assisted selection of Dezhou donkeys.The polymorphisms of NCAPG-DCAF16 region in Dezhou donkeys were detected by DNA pool sequencing technology.Based on the results of DNA pool sequencing,mass-array system was used to genotype the detected SNPs in 227 Dezhou donkeys.Association analysis between the SNPs of NCAPG-DCAF16 region and the growth traits at birth,3 months old and 6 months old were performed.The results showed that:1)Four SNPs were detected in NCAPGgene,rs1(T>C)in the 9 th intron,rs2(A>G)in the 11 th intron,rs4(C>G)in the 19 th intron,and rs5(C>G)in the 8 th intron.A synonymous mutation was found in the 2 nd exon of DCAF16 gene,and the site was rs008(A>G).2)The correlation analysis at birth revealed that the average rump length of the individuals with CC genotype at the rs1 was significantly higher than those with CT genotype at birth(P<0.05),the phenotypic values of individuals with different genotypes at 3 months old had no significant difference(P>0.05).At 6 months old,the average chest width of individuals with TT genotype was extremely significantly different from those with CC genotype(P<0.01),and the average shin circumference of individuals with TT and CT genotypes was significantly higher than those with CC genotype(P<0.05).3)The correlation analysis of rs4 locus indicated that the average chest depth of individuals with GG genotype was significantly higher than those with GC genotype at birth(P<0.05).At 3 months old,the average phenotypic values of individuals with different genotypes was not significantly different(P>0.05).The average chest width and shin circumference of individuals with CC genotype at the age of 6 months were significantly higher than those with GG genotype(P<0.05).4)The results of rs008 locus correlation analysis showed that there was no significant difference in phenotypic values among individuals with different genotypes at birth(P>0.05).The body weight,body height and rump height of individuals with AA and GA genotypes were significantly higher than those with GG genotypes at the age of 3 months(P<0.05).At 6 months old,the body height and chest circumference of individuals with AA and GA genotypes were extremely significantly higher than those with GG genotype(P<0.01).The difference in chest depth and rump height between individuals with GA and GG genotypes was extremely significantly different(P<0.01).The rump width of individuals with GA genotype was significantly higher than those with GG and AA genotypes(P<0.05).5)According to the result of linkage disequilibrium analysis,rs1,rs2,rs4 and rs5 had 5 combination genotypes in Dezhou donkeys.The results of association analysis displayed that the average chest width of individuals with TTAACCCC genotype was significantly higher than those with CCGGGGGG genotype at 6 months old(P <0.05).In summary,the 5 SNPs in the NCAPG-DCAF16 region of the Dezhou population have the significant effects on growth traits,especially the rs008 locus has a significant correlation with the important growth traits such as body weight and body height,which can be used as genetic markers to improve the breeding efficiency in Dezhou donkeys.
The study aimed to investigate the genetic polymorphisms of NCAPG-DCAF16 region in Dezhou donkeys and their associations with growth traits,which can help to mine significant genetic markers for molecular marker assisted selection of Dezhou donkeys.The polymorphisms of NCAPG-DCAF16 region in Dezhou donkeys were detected by DNA pool sequencing technology.Based on the results of DNA pool sequencing,mass-array system was used to genotype the detected SNPs in 227 Dezhou donkeys.Association analysis between the SNPs of NCAPG-DCAF16 region and the growth traits at birth,3 months old and 6 months old were performed.The results showed that:1)Four SNPs were detected in NCAPGgene,rs1(T>C)in the 9 th intron,rs2(A>G)in the 11 th intron,rs4(C>G)in the 19 th intron,and rs5(C>G)in the 8 th intron.A synonymous mutation was found in the 2 nd exon of DCAF16 gene,and the site was rs008(A>G).2)The correlation analysis at birth revealed that the average rump length of the individuals with CC genotype at the rs1 was significantly higher than those with CT genotype at birth(P<0.05),the phenotypic values of individuals with different genotypes at 3 months old had no significant difference(P>0.05).At 6 months old,the average chest width of individuals with TT genotype was extremely significantly different from those with CC genotype(P<0.01),and the average shin circumference of individuals with TT and CT genotypes was significantly higher than those with CC genotype(P<0.05).3)The correlation analysis of rs4 locus indicated that the average chest depth of individuals with GG genotype was significantly higher than those with GC genotype at birth(P<0.05).At 3 months old,the average phenotypic values of individuals with different genotypes was not significantly different(P>0.05).The average chest width and shin circumference of individuals with CC genotype at the age of 6 months were significantly higher than those with GG genotype(P<0.05).4)The results of rs008 locus correlation analysis showed that there was no significant difference in phenotypic values among individuals with different genotypes at birth(P>0.05).The body weight,body height and rump height of individuals with AA and GA genotypes were significantly higher than those with GG genotypes at the age of 3 months(P<0.05).At 6 months old,the body height and chest circumference of individuals with AA and GA genotypes were extremely significantly higher than those with GG genotype(P<0.01).The difference in chest depth and rump height between individuals with GA and GG genotypes was extremely significantly different(P<0.01).The rump width of individuals with GA genotype was significantly higher than those with GG and AA genotypes(P<0.05).5)According to the result of linkage disequilibrium analysis,rs1,rs2,rs4 and rs5 had 5 combination genotypes in Dezhou donkeys.The results of association analysis displayed that the average chest width of individuals with TTAACCCC genotype was significantly higher than those with CCGGGGGG genotype at 6 months old(P <0.05).In summary,the 5 SNPs in the NCAPG-DCAF16 region of the Dezhou population have the significant effects on growth traits,especially the rs008 locus has a significant correlation with the important growth traits such as body weight and body height,which can be used as genetic markers to improve the breeding efficiency in Dezhou donkeys.
引文
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[11]SETOGUCHI K,WATANABE T,WEIKARD R,et al.The SNP c.1326T>G in the non-SMC condensin Icomplex,subunit G(NCAPG)gene encoding ap.Ile442Met variant is associated with an increase in body frame size at puberty in cattle[J].Anim Genet,2011,42(6):650-655.
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[14]WEIKARD R,ALTMAIER E,SUHRE K,et al.Metabolomic profiles indicate distinct physiological pathways affected by two loci with major divergent effect on Bos taurus growth and lipid deposition[J].Physiol Genomics,2010,42A(2):79-88.
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[17]ZHANG W G,LI J Y,GUO Y,et al.Multi-strategy genome-wide association studies identify the DCAF16-NCAPG region as a susceptibility locus for average daily gain in cattle[J].Sci Rep,2016,6:38073.
[18]LIU Y,DUAN X Y,CHEN S,et al.NCAPGis differentially expressed during longissimus muscle development and is associated with growth traits in Chinese Qinchuan beef cattle[J].Genet Mol Biol,2015,38(4):450-456.
[19]AL-MAMUN H A,KWAN P,CLARK S A,et al.Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6to human and bovine genomic regions affecting height and weight[J].Genet Sel Evol,2015,47(1):66.
[20]GUTIRREZ-GIL B,ESTEBAN-BLANCO C,WIE-NER P,et al.High-resolution analysis of selection sweeps identified between fine-wool Merino and coarse-wool Churra sheep breeds[J].Genet Sel Evol,2017,49(1):81.
[21]FARIELLO M I,SERVIN B,TOSSER-KLOPP G,et al.Selection signatures in worldwide sheep populations[J].PLoS One,2014,9(8):e103813.
[22]ROCHUS C M,TORTEREAU F,PLISSON-PETITF,et al.Revealing the selection history of adaptive loci using genome-wide scans for selection:an example from domestic sheep[J].BMC Genomics,2018,19(1):71.
[23]CARNEIRO M,HU D,ARCHER J,et al.Dwarfism and altered craniofacial development in rabbits is caused by a 12.1kb deletion at the HMGA2locus[J].Genetics,2017,205(2):955-965.
[24]SIGNER-HASLER H,FLURY C,HAASE B,et al.Agenome-wide association study reveals loci influencing height and other conformation traits in horses[J].PLoS One,2012,7(5):e37282.
[25]TETENS J,WIDMANN P,KHN C,et al.A genome-wide association study indicates LCORL/NCAPGas a candidate locus for withers height in German Warmblood horses[J].Anim Genet,2013,44(4):467-471.
[26]BOYKO A R,BROOKS S A,BEHAN-BRAMAN A,et al.Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds[J].BMC Genomics,2014,15(1):259.
[27]SEVANE N,DUNNER S,BOADO A,et al.Polymorphisms in ten candidate genes are associated with conformational and locomotive traits in Spanish Purebred horses[J].J Appl Genet,2017,58(3):355-361.
[28]周楠,韩国才,柴晓峰,等.驴的产肉、理化指标及加工特性比较研究[J].畜牧兽医学报,2015,46(12):2314-2321.ZHOU N,HAN G C,CHAI X F,et al.A comparative study of donkey meat production,physicochemical indicators and processing properties[J].Acta Veterinaria et Zootechnica Sinica,2015,46(12):2314-2321.(in Chinese)
[29]侯文通.现代马学[M].北京:中国农业出版社,2013.HOU W T.Modern equine science[M].Beijing:China Agriculture Press,2013.(in Chinese)
[30]AKEY J,JIN L,XIONG M M.Haplotypes vs single marker linkage disequilibrium tests:what do we gain?[J].Eur J Hum Genet,2001,9(4):291-300.
[31]LINDHOLM-PERRY A K,SEXTEN A K,KUEHNL A,et al.Association,effects and validation of polymorphisms within the NCAPG-LCORLlocus located on BTA6with feed intake,gain,meat and carcass traits in beef cattle[J].BMC Genet,2011,12(1):103.
[32]STAIGER E A,AL ABRI M A,PFLUG K M,et al.Skeletal variation in Tennessee Walking Horses maps to the LCORL/NCAPGgene region[J].Phys Genomics,2016,48(5):325-335.
[33]CHANG K C.Critical regulatory domains in intron 2of a porcine sarcomeric myosin heavy chain gene[J].JMuscle Res Cell Motil,2000,21(5):451-461.
[34]BEAUCHAMP N J,DALY M E,MAKRIS M,et al.A novel mutation in intron K of the PROS1gene causes aberrant RNA splicing and is a common cause of protein S deficiency in a UK thrombophilia cohort[J].Thromb Haemost,1998,79(6):1086-1091.
[35]HIRSCHEY M D,SHIMAZU T,GOETZMAN E,et al.SIRT3regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation[J].Nature,2010,464(7285):121-125.
[36]HIR H L,NOTT A,MOORE M J.How introns influence and enhance eukaryotic gene expression[J].Trends Biochem Sci,2003,28(4):215-220.
[37]XIANG G H,REN J L,HAI T,et al.Editing porcine IGF2regulatory element improved meat production in Chinese Bama pigs[J].Cell Mol Life Sci,2018,75(24):4619-4628.
[2]SEIPOLD S,PRILLER F C,GOLDSMITH P,et al.Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina[J].BMC Dev Biol,2009,9(1):40.
[3]WEN X Y,DUUS K M,FRIEDRICH T D,et al.The HIV1protein Vpr acts to promote G2cell cycle arrest by engaging a DDB1and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1as an adaptor[J].J Biol Chem,2007,282(37):27046-27057.
[4]HORIKOSHI M,YAGHOOTKAR H,MOOK-KAN-AMORI D O,et al.New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism[J].Nat Genet,2013,45(1):76-82.
[5]VAN DER VALK R J P,KREINER-MLLER E,KOOIJMAN M N,et al.A novel common variant in DCST2is associated with length in early life and height in adulthood[J].Hum Mol Genet,2015,24(4):1155-1168.
[6]WEEDON M N,LANGO H,LINDGREN C M,et al.Genome-wide association analysis identifies 20loci that influence adult height[J].Nat Genet,2008,40(5):575-583.
[7]SORANZO N,RIVADENEIRA F,CHINAPPEN-HORSLEY U,et al.Meta-analysis of genome-wide scans for human adult stature identifies novel loci and associations with measures of skeletal frame size[J].PLoS Genet,2009,5(4):e1000445.
[8]OKADA Y,KAMATANI Y,TAKAHASHI A,et al.A genome-wide association study in 19 633Japanese subjects identified LHX3-QSOX2and IGF1as adult height loci[J].Hum Mol Genet,2010,19(11):2303-2312.
[9]N'DIAYE A,CHEN G K,PALMER C D,et al.Identification,replication,and fine-mapping of loci associated with adult height in individuals of African ancestry[J].PLoS Genet,2011,7(10):e1002298.
[10]SNELLING W M,ALLAN M F,KEELE J W,et al.Genome-wide association study of growth in crossbred beef cattle[J].J Anim Sci,2010,88(3):837-848.
[11]SETOGUCHI K,WATANABE T,WEIKARD R,et al.The SNP c.1326T>G in the non-SMC condensin Icomplex,subunit G(NCAPG)gene encoding ap.Ile442Met variant is associated with an increase in body frame size at puberty in cattle[J].Anim Genet,2011,42(6):650-655.
[12]EBERLEIN A,TAKASUGA A,SETOGUCHI K,et al.Dissection of genetic factors modulating fetal growth in cattle indicates a substantial role of the non-SMC condensin I complex,subunit G(NCAPG)gene[J].Genetics,2009,183(3):951-964.
[13]SETOGUCHI K,FURUTA M,HIRANO T,et al.Cross-breed comparisons identified a critical 591-kb region for bovine carcass weight QTL(CW-2)on chromosome 6 and the Ile-442-Met substitution in NCAPGas a positional candidate[J].BMC Genet,2009,10(1):43.
[14]WEIKARD R,ALTMAIER E,SUHRE K,et al.Metabolomic profiles indicate distinct physiological pathways affected by two loci with major divergent effect on Bos taurus growth and lipid deposition[J].Physiol Genomics,2010,42A(2):79-88.
[15]WIDMANN P,REVERTER A,FORTES M R S,et al.A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle[J].BMC Genomics,2013,14(1):798.
[16]WIDMANN P,REVERTER A,WEIKARD R,et al.Systems biology analysis merging phenotype,metabolomic and genomic data identifies Non-SMC Condensin I Complex,Subunit G(NCAPG)and cellular maintenance processes as major contributors to genetic variability in bovine feed efficiency[J].PLoS One,2015,10(4):e0124574.
[17]ZHANG W G,LI J Y,GUO Y,et al.Multi-strategy genome-wide association studies identify the DCAF16-NCAPG region as a susceptibility locus for average daily gain in cattle[J].Sci Rep,2016,6:38073.
[18]LIU Y,DUAN X Y,CHEN S,et al.NCAPGis differentially expressed during longissimus muscle development and is associated with growth traits in Chinese Qinchuan beef cattle[J].Genet Mol Biol,2015,38(4):450-456.
[19]AL-MAMUN H A,KWAN P,CLARK S A,et al.Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6to human and bovine genomic regions affecting height and weight[J].Genet Sel Evol,2015,47(1):66.
[20]GUTIRREZ-GIL B,ESTEBAN-BLANCO C,WIE-NER P,et al.High-resolution analysis of selection sweeps identified between fine-wool Merino and coarse-wool Churra sheep breeds[J].Genet Sel Evol,2017,49(1):81.
[21]FARIELLO M I,SERVIN B,TOSSER-KLOPP G,et al.Selection signatures in worldwide sheep populations[J].PLoS One,2014,9(8):e103813.
[22]ROCHUS C M,TORTEREAU F,PLISSON-PETITF,et al.Revealing the selection history of adaptive loci using genome-wide scans for selection:an example from domestic sheep[J].BMC Genomics,2018,19(1):71.
[23]CARNEIRO M,HU D,ARCHER J,et al.Dwarfism and altered craniofacial development in rabbits is caused by a 12.1kb deletion at the HMGA2locus[J].Genetics,2017,205(2):955-965.
[24]SIGNER-HASLER H,FLURY C,HAASE B,et al.Agenome-wide association study reveals loci influencing height and other conformation traits in horses[J].PLoS One,2012,7(5):e37282.
[25]TETENS J,WIDMANN P,KHN C,et al.A genome-wide association study indicates LCORL/NCAPGas a candidate locus for withers height in German Warmblood horses[J].Anim Genet,2013,44(4):467-471.
[26]BOYKO A R,BROOKS S A,BEHAN-BRAMAN A,et al.Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds[J].BMC Genomics,2014,15(1):259.
[27]SEVANE N,DUNNER S,BOADO A,et al.Polymorphisms in ten candidate genes are associated with conformational and locomotive traits in Spanish Purebred horses[J].J Appl Genet,2017,58(3):355-361.
[28]周楠,韩国才,柴晓峰,等.驴的产肉、理化指标及加工特性比较研究[J].畜牧兽医学报,2015,46(12):2314-2321.ZHOU N,HAN G C,CHAI X F,et al.A comparative study of donkey meat production,physicochemical indicators and processing properties[J].Acta Veterinaria et Zootechnica Sinica,2015,46(12):2314-2321.(in Chinese)
[29]侯文通.现代马学[M].北京:中国农业出版社,2013.HOU W T.Modern equine science[M].Beijing:China Agriculture Press,2013.(in Chinese)
[30]AKEY J,JIN L,XIONG M M.Haplotypes vs single marker linkage disequilibrium tests:what do we gain?[J].Eur J Hum Genet,2001,9(4):291-300.
[31]LINDHOLM-PERRY A K,SEXTEN A K,KUEHNL A,et al.Association,effects and validation of polymorphisms within the NCAPG-LCORLlocus located on BTA6with feed intake,gain,meat and carcass traits in beef cattle[J].BMC Genet,2011,12(1):103.
[32]STAIGER E A,AL ABRI M A,PFLUG K M,et al.Skeletal variation in Tennessee Walking Horses maps to the LCORL/NCAPGgene region[J].Phys Genomics,2016,48(5):325-335.
[33]CHANG K C.Critical regulatory domains in intron 2of a porcine sarcomeric myosin heavy chain gene[J].JMuscle Res Cell Motil,2000,21(5):451-461.
[34]BEAUCHAMP N J,DALY M E,MAKRIS M,et al.A novel mutation in intron K of the PROS1gene causes aberrant RNA splicing and is a common cause of protein S deficiency in a UK thrombophilia cohort[J].Thromb Haemost,1998,79(6):1086-1091.
[35]HIRSCHEY M D,SHIMAZU T,GOETZMAN E,et al.SIRT3regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation[J].Nature,2010,464(7285):121-125.
[36]HIR H L,NOTT A,MOORE M J.How introns influence and enhance eukaryotic gene expression[J].Trends Biochem Sci,2003,28(4):215-220.
[37]XIANG G H,REN J L,HAI T,et al.Editing porcine IGF2regulatory element improved meat production in Chinese Bama pigs[J].Cell Mol Life Sci,2018,75(24):4619-4628.