玉山黑猪两种头型遗传机制的初步解析
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摘要
旨在检测"马脸"型和"狮子头"型玉山黑猪在基因组上的遗传分化信号,结合全基因组关联分析(GWAS),鉴别影响玉山黑猪两种头型的候选基因并探寻其可能的形成机理。本研究选取玉山黑猪国家保种场的24头"马脸"型个体和12头"狮子头"型个体,利用Illumina猪60KSNP芯片对这些个体进行扫描和基因分型。基于60K SNP芯片数据,检测"马脸"型和"狮子头"型两个类群间的遗传分化系数(Fst)。同时,进行病例-对照的GWAS分析和连锁不平衡(LD)分析,根据Fst、GWAS和LD分析结果确定重要候选基因。结果表明,两个群体间最强的遗传分化信号位于猪10号染色体,GWAS同样在该区域检测到显著的关联位点。LD及单倍型分析将置信区间锁定在该染色体11.76~12.05 Mb的一段290kb的区域。本研究基于猪60K芯片数据,通过遗传分化分析、全基因组关联分析和连锁不平衡分析等手段,初步推测RAB3GAP2和IASR2为影响玉山黑猪头型的候选基因,该结果为进一步解析中国地方猪不同头型的形成机制奠定了基础。
The aim of this study was to identify candidate genes affecting the two head types(longpointed head and short head)in Yushan Black pigs through conducting agenome-wide association study(GWAS)and a genome-wide scan for the selection signatures.Twenty-four pigs with longpointed head and 12 pigs with short head were selected from the national conservation farm of Yushan Black pigs and were genotyped using Porcine SNP 60 KBeadChips.The Fst value of each SNP was calculated to detect signatures of genetic differentiation between the two groups of pigs.Meanwhile,case-control GWAS and linkage disequilibrium(LD)analysis were performed to define confidence intervals and candidate genes based on Fst.The results showed that the most significant signature of genetic differentiation was located on Sus Scrofachromosome(SSC)10,and a genome-wide significant locus within the same region was also detected by GWAS.The most likely interval of this locus was defined by the LD block analysis,about 290 kb(from 11.76 to 12.05 Mb)on SSC10.By applying genetic differentiation analysis,genome-wide association study and linkage disequilibrium(LD)analysis,we speculated that candidate genes for head types were RAB3 GAP2 and IASR2 in Yushan Black pigs.The findings will contribute to reveal the genetic basis of phenotypic changes in head types in Chinese indigenous pigs.
The aim of this study was to identify candidate genes affecting the two head types(longpointed head and short head)in Yushan Black pigs through conducting agenome-wide association study(GWAS)and a genome-wide scan for the selection signatures.Twenty-four pigs with longpointed head and 12 pigs with short head were selected from the national conservation farm of Yushan Black pigs and were genotyped using Porcine SNP 60 KBeadChips.The Fst value of each SNP was calculated to detect signatures of genetic differentiation between the two groups of pigs.Meanwhile,case-control GWAS and linkage disequilibrium(LD)analysis were performed to define confidence intervals and candidate genes based on Fst.The results showed that the most significant signature of genetic differentiation was located on Sus Scrofachromosome(SSC)10,and a genome-wide significant locus within the same region was also detected by GWAS.The most likely interval of this locus was defined by the LD block analysis,about 290 kb(from 11.76 to 12.05 Mb)on SSC10.By applying genetic differentiation analysis,genome-wide association study and linkage disequilibrium(LD)analysis,we speculated that candidate genes for head types were RAB3 GAP2 and IASR2 in Yushan Black pigs.The findings will contribute to reveal the genetic basis of phenotypic changes in head types in Chinese indigenous pigs.
引文
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[20]MOOSA S,HAAGERUP A,GREGERSEN P A,et al.Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in IARS2[J].Am J Med Genet,2017,173(4):1102-1108.
[21]SOKABE M,OKADA A,YAO M,et al.Molecular basis of alanine discrimination in editing site[J].Proc Natl Acad Sci U S A,2005,102(33):11669-11674.
[22]PERLI E,GIORDANO C,TUPPEN H A L,et al.Isoleucyl-tRNA synthetase levels modulate the penetrance of a homoplasmic m.4277T>C mitochondrial tRNAIle mutation causing hypertrophic cardiomyopathy[J].Hum Mol Genet,2012,21(1):85-100.
[23]YIN J,LIU W,LI R,et al.IARS2silencing induces non-small cell lung cancer cells proliferation inhibition,cell cycle arrest and promotes cell apoptosis[J].Neoplasma,2016,63(1):64-71.
[24]FANG Z,WANG X Y,YAN Q,et al.Knockdown of IARS2suppressed growth of gastric cancer cells by regulating the phosphorylation of cell cycle-related proteins[J].Mol Cell Biochem,2018,443(1-2):93-100.
[25]HAGG S,GANNA A,VAN DER LAAN S W,et al.Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity[J].Hum Mol Genet,2015,24(23):6849-6860.
[26]GOMES R C,SILVA S L,CARVALHO M E,et al.Protein synthesis and degradation gene SNPs related to feed intake,feed efficiency,growth,and ultrasound carcass traits in Nellore cattle[J].Genet Mol Res,2013,12(3):2923-2936.
[2]国家畜禽遗传资源委员会.中国畜禽遗传资源志:猪志[M].北京:中国农业出版社,2011:157-160.National Livestock and Poultry Genetic Resources Committee.Animal genetic resources in China:Pigs[M].Beijing:China Agriculture Press,2011:157-160.(in Chinese)
[3]李秀领,杨松柏,唐中林,等.大白猪和通城猪全基因组选择性清扫分析[J].遗传,2012,34(10):1271-1281.LI X L,YANG S B,TANG Z L,et al.Genome-wide selective sweep analysis on Large White and Tongcheng pigs[J].Hereditas,2012,34(10):1271-1281.(in Chinese)
[4]WRIGHT S.Isolation by distance[J].Genetics,1943,28(2):114-138.
[5]REN J,MAO H,ZHANG Z,et al.A 6-bp deletion in the TYRP1gene causes the brown colouration phenotype in Chinese indigenous pigs[J].Heredity(Edinb),2011,106(5):862-868.
[6]REN J,DUAN Y Y,QIAO R M,et al.A missense mutation in PPARD causes a major QTL effect on ear size in pigs[J].PLoS Genet,2011,7(5):e1002043.
[7]YANG B,ZHANG W C,ZHANG Z Y,et al.Genomewide association analyses for fatty acid composition in porcine muscle and abdominal fat tissues[J].PLoS One,2013,8(6):e65554.
[8]阮国荣,龙毅,宿英,等.全基因组关联分析(GWAS)鉴别猪腹股沟/阴囊疝易感基因[J].畜牧兽医学报,2014,45(11):1775-1783.RUAN G R,LONG Y,SU Y,et al.Genome-wide association study on identifying susceptibility loci for pig inguinal/scrotal hernia[J].Acta Veterinaria et Zootechnica Sinica,2014,45(11):1775-1783.(in Chinese)
[9]杨杰,周李生,刘先先,等.莱芜猪与杜长大三元杂交猪肉质性状种质资源比较研究[J].畜牧兽医学报,2014,45(11):1752-1759.YANG J,ZHOU L S,LIU X X,et al.A comparative study of meat quality traits between Laiwu and DLY Pigs[J].Acta Veterinaria et Zootechnica Sinica,2014,45(11):1752-1759.(in Chinese)
[10]WEIR B S,COCKERHAM C C.Estimating f-statistics for the analysis of population structure[J].Evolution,1984,38(6):1358-1370.
[11]ZHOU X,STEPHENS M.Genome-wide efficient mixed-model analysis for association studies[J].Nat Genet,2012,44(7):821-824.
[12]WANG C B,WANG X P,TANG J H,et al.Genomewide association studies for two exterior traits in Chinese Dongxiang spotted pigs[J].Anim Sci J,2018,doi:10.1111/asj.13003.
[13]BARRETT J C,FRY B,MALLER J,et al.Haploview:Analysis and visualization of LD and haplotype maps[J].Bioinformatics,2005,21(2):263-265.
[14]AI H S,FANG X D,YANG B,et al.Adaptation and possible ancient interspecies introgression in pigs identified by whole-genome sequencing[J].Nat Genet,2015,47(3):217-225.
[15]NAGANO F,SASAKI T,FUKUI K,et al.Molecular cloning and characterization of the noncatalytic subunit of the Rab3subfamily-specific GTPase-activating protein[J].J Biol Chem,1998,273(38):24781-24785.
[16]HANDLEY M T,MORRIS-ROSENDAHL D J,BROWN S,et al.Mutation spectrum in RAB3GAP1,RAB3GAP2,and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome[J].Hum Mutat,2013,34(5):686-696.
[17]ALIGIANIS I A,MORGAN N V,MIONE M,et al.Mutation in Rab3 GTPase-activating protein(RAB3GAP)noncatalytic subunit in a kindred with martsolf syndrome[J].Am J Hum Genet,2006,78(4):702-707.
[18]BORCK G,WUNRAM H,STEIERT A,et al.A homozygous RAB3GAP2mutation causes Warburg Micro syndrome[J].Hum Genet,2011,129(1):45-50.
[19]SCHWARTZENTRUBER J,BUHAS D,MAJEWSKI J,et al.Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA Synthetase IARS2in patients with cataracts,growth hormone deficiency with short stature,partial sensorineural deafness,and peripheral neuropathy or with Leigh syndrome[J].Hum Mutat,2014,35(11):1285-1289.
[20]MOOSA S,HAAGERUP A,GREGERSEN P A,et al.Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in IARS2[J].Am J Med Genet,2017,173(4):1102-1108.
[21]SOKABE M,OKADA A,YAO M,et al.Molecular basis of alanine discrimination in editing site[J].Proc Natl Acad Sci U S A,2005,102(33):11669-11674.
[22]PERLI E,GIORDANO C,TUPPEN H A L,et al.Isoleucyl-tRNA synthetase levels modulate the penetrance of a homoplasmic m.4277T>C mitochondrial tRNAIle mutation causing hypertrophic cardiomyopathy[J].Hum Mol Genet,2012,21(1):85-100.
[23]YIN J,LIU W,LI R,et al.IARS2silencing induces non-small cell lung cancer cells proliferation inhibition,cell cycle arrest and promotes cell apoptosis[J].Neoplasma,2016,63(1):64-71.
[24]FANG Z,WANG X Y,YAN Q,et al.Knockdown of IARS2suppressed growth of gastric cancer cells by regulating the phosphorylation of cell cycle-related proteins[J].Mol Cell Biochem,2018,443(1-2):93-100.
[25]HAGG S,GANNA A,VAN DER LAAN S W,et al.Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity[J].Hum Mol Genet,2015,24(23):6849-6860.
[26]GOMES R C,SILVA S L,CARVALHO M E,et al.Protein synthesis and degradation gene SNPs related to feed intake,feed efficiency,growth,and ultrasound carcass traits in Nellore cattle[J].Genet Mol Res,2013,12(3):2923-2936.