基于单倍型肉牛屠宰性状全基因组关联分析研究

doi:10.11843/j.issn.0366-6964.2022.12.010

Abstract

Abstract: Haplotypes have a stronger linkage disequilibrium (LD) relationship with quantitative trait loci (QTLs). Haplotypes tend to have higher application value in gene mapping and searching for causal mutations. In order to evaluate the role of haplotype markers in genome studies, a total of 1 478 individuals in Huaxi cattle with an average age of 24 months, including 1 333 bulls and 145 cows, were slaughtered from 2008 to 2021. The LD thresholds was set at r²>0.3 and the number of fixed-SNPs was 5 for haploblock construction with 770K chip data, GWAS using GCTA with mixed linear model based on SNP and haplotype (a total of 3 markers were used: SNP marker and two types of haplotype marker) were performed on Huaxi cattle to detect the significant SNPs, haploblocks and candidate genes associated with LW and DP traits. In addition, the GWAS results of the 3 markers were compared to evaluate the advantages and disadvantages of the 3 markers. The results showed that 16 significant SNPs and haploblocks were detected in the whole genome, mainly distributed on chromosome 1, 5, 6, 14, 16, 17 and 28. A total of 10 candidate genes, such as FAM184B,PPM1K,LCORL,RIMS2 were identified, which significantly associated with the slaughter traits. And 3 candidate genes identified by SNP markers could also be identified by haplotype method, most of the significant loci or regions identified by haplotype were located within the gene. Among the two haplotype construction methods, the LD-based construction method identified more candidate genes than the one based on the fixed-SNPs for GWAS. In this study, the results showed that haplotype-based GWAS can comprehensively consider the LD between SNPs and can better reveal the genetic structure of complex traits.

Key words: beef cattle, haplotype, SNP, genome-wide association study, linkage disequilibrium

CLC Number:

S823.2

LI Hongwei, XU Lingyang, WANG Zezhao, CAI Wentao, ZHU Bo, CHEN Yan, GAO Xue, ZHANG Lupei, GAO Huijiang, LI Junya. Genome-wide Association Study of Slaughter Traits Based on Haplotype in Beef Cattle[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(12): 4232-4243.

References 49

[1]	RISCH N,MERIKANGAS K.The future of genetic studies of complex human diseases[J]. Science, 1996, 273(5281):1516-1517.
[2]	COCKRAM J,WHITE J,ZULUAGA D L,et al.Genome-wide association mapping to candidate poly-morphism resolution in the unsequenced barley genome[J].Proc Natl Acad Sci U S A,2010,107(50):21611-21616.
[3]	LIU N,XUE Y D,GUO Z Y,et al.Genome-wide association study identifies candidate genes for starch content regulation in maize kernels[J].Front Plant Sci,2016,7:1046.
[4]	REMINGTON D L,THORNSBERRY J M,MATSUOKA Y,et al.Structure of linkage disequilibrium and phenotypic associations in the maize genome[J].Proc Natl Acad Sci U S A,2001,98(20):11479-11484.
[5]	THORNSBERRY J M,GOODMAN M M,DOEBLEY J,et al.Dwarf8 polymorphisms associate with variation in flowering time[J].Nat Genet,2001,28(3):286-289.
[6]	常天鹏,夏江威,宝金山,等.利用两种统计模型对中国肉用西门塔尔牛屠宰性状的全基因组关联分析[J].畜牧兽医学报,2018,49(4):833-840.CHANG T P,XIA J W,BAO J S,et al.Genome-wide association study for carcass traits using two statistic models in Chinese simmental beef cattle[J].Acta Veterinaria et Zootechnica Sinica,2018,49(4):833-840.(in Chinese)
[7]	段星海,安炳星,杜丽丽,等.中国肉用西门塔尔牛生长曲线参数的全基因组关联分析[J].畜牧兽医学报, 2021, 52(5):1267-1277.DUAN X H,AN B X,DU L L,et al.Genome-wide association study of growth curve parameters in Chinese simmental beef cattle[J].Acta Veterinaria et Zootechnica Sinica,2021,52(5):1267-1277.(in Chinese)
[8]	刘晓静,刘璐,王杰,等.鸡血糖性状的全基因组关联分析[J].畜牧兽医学报,2020,51(6):1187-1195.LIU X J,LIU L,WANG J,et al.Genome-wide association study of chicken blood glucose traits using whole genome resequencing[J].Acta Veterinaria et Zootechnica Sinica,2020,51(6):1187-1195.(in Chinese)
[9]	米布农,张立果,乌日汉,等.戴瑞奶绵羊产奶性状的全基因组关联分析[J].畜牧兽医学报,2021,52(11):3294-3303.MI B N,ZHANG L G,BAI U,et al.Genome-wide association study of milk production traits in dairy meade sheep[J].Acta Veterinaria et Zootechnica Sinica,2021,52(11):3294-3303.(in Chinese)
[10]	XIANG R D,MACLEOD I M,DAETWYLER H D,et al.Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations[J].Nat Commun,2021,12(1):860.
[11]	YU J M,PRESSOIR G,BRIGGS W H,et al.A unified mixed-model method for association mapping that accounts for multiple levels of relatedness[J].Nat Genet,2006,38(2):203-208.
[12]	LIPKA A E,KANDIANIS C B,HUDSON M E,et al.From association to prediction:statistical methods for the dissection and selection of complex traits in plants[J].Curr Opin Plant Biol,2015,24:110-118.
[13]	ZHANG X Y,YAZAKI J,SUNDARESAN A,et al.Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis[J].Cell,2006,126(6):1189-1201.
[14]	PRYCE J E,BOLORMAA S,CHAMBERLAIN A J,et al.A validated genome-wide association study in 2 dairy cattle breeds for milk production and fertility traits using variable length haplotypes[J].J Dairy Sci,2010,93(7): 3331-3345.
[15]	TRÉGOUËT D A,KÖNIG I R,ERDMANN J,et al.Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease[J].Nat Genet,2009,41(3):283-285.
[16]	BARDEL C,DANJEAN V,HUGOT J P,et al.On the use of haplotype phylogeny to detect disease susceptibility loci[J].BMC Genet,2005,6(1):24.
[17]	JIANG Y,SCHMIDT R H,REIF J C.Haplotype-based genome-wide prediction models exploit local epistatic interactions among markers[J].G3 (Bethesda),2018,8(5):1687-1699.
[18]	N'DIAYE A,HAILE J K,CORY A T,et al.Single marker and haplotype-based association analysis of semolina and pasta colour in elite durum wheat breeding lines using a high-density consensus map[J].PLoS One,2017,12(10): e0170941.
[19]	MEUWISSEN T H E,GODDARD M E.Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci[J].Genetics,2000,155(1):421-430.
[20]	TEMPLETON A R.A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping or DNA sequencing.V.Analysis of case/control sampling designs:Alzheimer’s disease and the apoprotein E locus[J].Genetics,1995,140(1):403-409.
[21]	CHEN H L,HAO Z Y,ZHAO Y F,et al.A fast-linear mixed model for genome-wide haplotype association analysis:application to agronomic traits in maize[J].BMC Genomics,2020,21(1):151.
[22]	CHEN S L,LIU F,WU W X,et al.A SNP-based GWAS and functional haplotype-based GWAS of flag leaf-related traits and their influence on the yield of bread wheat (Triticum aestivum L.)[J].Theor Appl Genet,2021, 134(12): 3895-3909.
[23]	ZHANG H,SHEN L Y,XU Z C,et al.Haplotype-based genome-wide association studies for carcass and growth traits in chicken[J].Poult Sci,2020,99(5):2349-2361.
[24]	ARAUJO A C,CARNEIRO P L S,ALVARENGA A B,et al.Haplotype-based single-step GWAS for yearling temperament in American Angus cattle[J].Genes,2022,13(1):17.
[25]	WU P X,WANG K,ZHOU J,et al.A combined GWAS approach reveals key loci for socially-affected traits in Yorkshire pigs[J].Commun Biol,2021,4(1):891.
[26]	GILMOUR A R,THOMPSON R,CULLIS B R.Average information REML:an efficient algorithm for variance parameter estimation in linear mixed models[J].Biometrics,1995,51(4):1440-1450.
[27]	PURCELL S,NEALE B,TODD-BROWN K,et al.PLINK:a tool set for whole-genome association and population-based linkage analyses[J].Am J Hum Genet,2007,81(3):559-575.
[28]	BROWNING B L,ZHOU Y,BROWNING S R.A one-penny imputed genome from next-generation reference panels[J].Am J Hum Genet,2018,103(3):338-348.
[29]	HILL W G,ROBERTSON A.Linkage disequilibrium in finite populations[J].Theor Appl Genet,1968,38(6):226-231.
[30]	HILL W G.Estimation of effective population size from data on linkage disequilibrium[J].Genet Res,1981,38(3): 209-216.
[31]	MEUWISSEN T H E,ODEGARD J,ANDERSEN-RANBERG I,et al.On the distance of genetic relationships and the accuracy of genomic prediction in pig breeding[J].Genet Sel Evol,2014,46(1):49.
[32]	YANG J,LEE S H,GODDARD M E,et al.GCTA:a tool for genome-wide complex trait analysis[J].Am J Hum Genet,2011,88(1):76-82.
[33]	HAYES B.Overview of statistical methods for genome-wide association studies (GWAS)[J].Methods Mol Biol,2013,1019:149-169.
[34]	GILMOUR A,GOGEL B,CULLIS B,et al.ASReml user guide release 3.0.VSN international Ltd[J].2009:https://www.scienceopen.com/document?vid=eb4bebf5-3221-45b0-93ee-e90ea245a4ba.
[35]	DUNCAN L E,RATANATHARATHORN A,AIELLO A E,et al.Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability[J].Mol Psychiatry,2018,23(3):666-673.
[36]	BOUAZIZ M,AMBROISE C,GUEDJ M.Accounting for population stratification in practice:a comparison of the main strategies dedicated to genome-wide association studies[J].PLoS One,2011,6(12):e28845.
[37]	ARMSTRONG D L,ZIDOVETZKI R,ALARCÓN-RIQUELME M E,et al.GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region[J].Genes Immun,2014,15(6):347-354.
[38]	BANI-FATEMI A,GRAFF A,ZAI C,et al.GWAS analysis of suicide attempt in schizophrenia:main genetic effect and interaction with early life trauma[J].Neurosci Lett,2016,622:102-106.
[39]	LI S P,QIAN J,YANG Y,et al.GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers[J].PLoS Genet,2012,8(7):e1002791.
[40]	LIU Z X,BAI C Y,SHI L L,et al.Detection of selection signatures in South African Mutton Merino sheep using whole-genome sequencing data[J].Anim Genet,2022,53(2):224-229.
[41]	XIA J W,FAN H Z,CHANG T P,et al.Searching for new loci and candidate genes for economically important traits through gene-based association analysis of Simmental cattle[J].Sci Rep,2017,7(1):42048.
[42]	ABO-ISMAIL M K,LANSINK N,AKANNO E,et al.Development and validation of a small SNP panel for feed efficiency in beef cattle[J].J Anim Sci,2018,96(2):375-397.
[43]	ZHANG W G,XU L Y,GAO H J,et al.Detection of candidate genes for growth and carcass traits using genome-wide association strategy in Chinese Simmental beef cattle[J].Anim Prod Sci,2016,58(2):224-233.
[44]	MIAO J,WANG X,BAO J,et al.Multimarker and rare variants genomewide association studies for bone weight in Simmental cattle[J].J Anim Breed Genet,2018,135(3):159-169.
[45]	WANG X Q,MIAO J,XIA J W,et al.Identifying novel genes for carcass traits by testing G×E interaction through genome-wide meta-analysis in Chinese Simmental beef cattle[J].Livest Sci,2018,212:75-82.
[46]	LIU Y,XU L,WANG Z Z,et al.Genomic prediction and association analysis with models including dominance effects for important traits in Chinese simmental beef cattle[J].Animals (Basel),2019,9(12):1055.
[47]	ALBAGHA O M E,WANI S E,VISCONTI M R,et al.Genome-wide association identifies three new susceptibility loci for Paget’s disease of bone[J].Nat Genet,2011,43(7):685-689.
[48]	LINDHOLM-PERRY A K,SEXTEN A K,KUEHN L A,et al.Association,effects and validation of polymorphisms within the NCAPG - LCORL locus located on BTA6 with feed intake,gain,meat and carcass traits in beef cattle[J].BMC Genet,2011,12(1):103.
[49]	KAMATH R A D,BENSON M D.EphB3 as a potential mediator of developmental and reparative osteogenesis[J].Cells Tissues Organs,2021:doi: 10.1159/000520369.

Genome-wide Association Study of Slaughter Traits Based on Haplotype in Beef Cattle

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