利用可变窗口FST方法检测不同尾型呼伦贝尔羊尾部脂肪沉积相关基因

doi:10.11843/j.issn.0366-6964.2018.07.004

摘要/Abstract

摘要：

旨在挖掘控制绵羊尾型的候选基因，揭示绵羊尾部脂肪沉积机理。本研究利用呼伦贝尔羊两个不同尾型品系的288个个体，其中大尾羊142只和小尾羊146只，基于Illumina Ovine SNP 600K SNP芯片数据计算全基因组单点F_ST值。通过三次光滑样条估计方法确定可变窗口大小和数量，构建W统计量并进行统计检验，鉴定选择区段和注释相关基因。结果，在基因组范围内共确定了23 144个可变窗口，其中区间最大的窗口位于chr12：35 241 750~43 798 950 bp处，其大小为8.56 Mb，并包含775个SNPs。经检测发现，27个窗口达到极显著水平（P<0.001），并鉴定了337个候选基因，其中22个是与已发现的脂肪代谢相关的基因。通过GO分析发现，这些候选基因主要富集在细胞内组成成分、有机氮化合物代谢过程以及小分子代谢过程等条目。通过可变窗口F_ST法能够有效检测到受选择的基因与绵羊尾部脂肪沉积相关。这些基因可以作为绵羊尾型选育的候选基因，为培育短尾绵羊提供重要依据。

Abstract:

The aims of this study were to reveal the genetic mechanism of fat deposition in the tail of sheep, and to explore the candidate genes involved in sheep tail fat. A total of 288 individuals from two lines of Hulun Buir sheep with different tail types were used to identify candidate genes controlling different tail types of sheep. These individuals included 142 fat-tailed and 146 thin-tailed sheep. The whole-genome single locus F_ST values were calculated based on the Illumina Ovine 600K SNP genotype data. The cubic smoothing spline method was used to define the numbers and sizes of variable windows. A total of 23 144 variable windows were identified within the whole genome. The largest window with 775 SNPs was located at chr12:35 241 750-43 798 950 bp, with a size of 8.56 Mb. The W statistic was constructed to detect the windows with selection signature. Twenty-seven of variable windows reached extremely significant level(P<0.001). After annotation, these windows harbored 337 candidate genes, of which 22 were related to the fat metabolism. Through GO analysis, these candidate genes were mainly enriched in the intracellular components, organonitrogen compound metabolic process and small molecule metabolic process. The F_ST method with variable windows was used to effectively identify candidate genes associated with fat deposition in the tail of sheep. These genes can be used to breed a new sheep breed with small size. The results will provide an important reference for breeding short-tailed sheep.

中图分类号:

S826.2

张统雨, 樊红樱, 朱才业, 刘家鑫, 邓天宇, 杜立新, 王立贤, 赵福平. 利用可变窗口F_ST方法检测不同尾型呼伦贝尔羊尾部脂肪沉积相关基因[J]. 畜牧兽医学报, 2018, 49(7): 1354-1365.

ZHANG Tong-yu, FAN Hong-ying, ZHU Cai-ye, LIU Jia-xin, DENG Tian-yu, DU Li-xin, WANG Li-xian, ZHAO Fu-ping. Identification of Candidate Genes Involved in Fat Deposition in Hulun Buir Sheep Tails Using F_ST within the Variable Window Sizes[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(7): 1354-1365.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: https://www.xmsyxb.com/CN/10.11843/j.issn.0366-6964.2018.07.004

https://www.xmsyxb.com/CN/Y2018/V49/I7/1354

参考文献

[1] 国家畜禽遗传资源委员会.中国畜禽遗传资源志·羊志[M].北京:中国农业出版社,2011.
China National Commission of Animal Genetic Resources.Animal genetic resources in China? Sheep and goat[M].Beijing:Chinese Agricultural Press,2011. (in Chinese)
[2] 甘尚权,张伟,宋天增,等.X染色体一处新发现的SNP位点在脂尾(臀)、瘦尾绵羊群体中的多态检测及分析[J].西南农业学报,2013,26(5):2066-2070.
GAN S Q,ZHANG W,SONG T Z,et al.Polymorphism detection and analysis of novel SNP on X chromosome between fat-tailed and thin-tailed sheep breeds[J].Southwest China Journal of Agricultural Sciences,2013,26(5):2066-2070. (in Chinese)
[3] 刘真,王慧华,刘瑞凿,等.不同尾型绵羊全基因组选择信号检测[J].畜牧兽医学报,2015,46(10):1721-1732.
LIU Z,WANG H H,LIU R Z,et al.Genome-wide detection of selection signatures of distinct tail types in sheep populations[J].Acta Veterinaria et Zootechnica Sinica,2015,46(10):1721-1732. (in Chinese)
[4] 甘尚权,张伟,沈敏,等.绵羊X染色体59383635位点多态性与脂尾性状的相关性分析[J].遗传,2013,35(10):1209-1216.
GAN S Q,ZHANG W,SHEN M,et al.Correlation analysis between polymorphism of the 59383635th locus on X chromosome and fat-tail trait in sheep[J].Hereditas,2013,35(10):1209-1216. (in Chinese)
[5] 马云龙,张勤,丁向东.利用高密度SNP检测不同猪品种间X染色体选择信号[J].遗传,2012,34(10):1251-1260.
MA Y L,ZHANG Q,DING X D.Detecting selection signatures on X chromosome in pig through high density SNPs[J].Hereditas,2012,34(10):1251-1260. (in Chinese)
[6] NIELSEN R.Molecular signatures of natural selection[J].Annu Rev Genet,2005,39:197-218.
[7] HOLSINGER K E,WEIR B S.Genetics in geographically structured populations:defining,estimating and interpreting F_ST[J].Nat Rev Genet,2009,10(9):639-650.
[8] 曾滔,赵福平,王光凯,等.基于群体分化指数F_ST的绵羊全基因组选择信号检测[J].畜牧兽医学报,2013,44(12):1891-1899.
ZENG T,ZHAO F P,WANG G K,et al.Genome-wide detection of selection signatures in sheep populations with use of population differentiation index F_ST[J].Acta Veterinaria et Zootechnica Sinica,2013,44(12):1891-1899. (in Chinese)
[9] KIJAS J W,LENSTRA J A,HAYES B,et al.Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection[J].PLoS Biol,2012,10(2):e1001258.
[10] GORKHALI N A,DONG K Z,YANG M,et al.Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas[J].Sci Rep,2016,6:29963.
[11] YUAN Z H,LIU E,LIU Z,et al.Selection signature analysis reveals genes associated with tail type in Chinese indigenous sheep[J].Anim Genet,2017,48(1):55-66.
[12] MOIOLI B,PILLA F,CIANI E.Signatures of selection identify loci associated with fat tail in sheep[J].J Anim Sci,2015,93(10):4660-4669.
[13] MORADI M H,NEJATI-JAVAREMI A,MORADI-SHAHRBABAK M,et al.Genomic scan of selective sweeps in thin and fat tail sheep breeds for identifying of candidate regions associated with fat deposition[J].BMC Genet,2012,13:10.
[14] 任鑫亮,高雅英.呼伦贝尔羊的特性及饲养管理措施[J].畜牧与饲料科学,2012,33(3):122-123.
REN X L,GAO Y Y.Characteristics of Hulun Buir Sheep and breeding management measures[J].Animal Husbandry and Feed Science,2012,33(3):122-123. (in Chinese)
[15] 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.
[16] BROWNING B L,BROWNING S R.A unified approach to genotype imputation and haplotype-phase inference for large data sets of trios and unrelated individuals[J].Am J Hum Genet,2009,84(2):210-223.
[17] WEIR B S,COCKERHAM C C.Estimating F-statistics for the analysis of population structure[J].Evolution,1984,38(6):1358-1370.
[18] BEISSINGER T M,ROSA G J M,KAEPPLER S M,et al.Defining window-boundaries for genomic analyses using smoothing spline techniques[J].Genet Sel Evol,2015,47(1):30.
[19] EDEN E,NAVON R,STEINFELD I,et al.GOrilla:a tool for discovery and visualization of enriched GO terms in ranked gene lists[J].BMC Bioinformatics,2009,10:48.
[20] R CORE TEAM.R:A language and environment for statistical computing[M].Vienna,Austria:the R Foundation,2015,14:12-21.
[21] LI J M,LU C L,CHENG M C,et al.Role of the DLGAP2 gene encoding the SAP90/PSD-95-associated protein 2 in schizophrenia[J].PLoS One,2014,9(1):e85373.
[22] 李宏图,秦秀娟,乌恩巴雅尔,等.呼伦贝尔羊"短尾"品系的外形分析[J].中国草食动物,2006(S1):148-149.
LI H T,QIN X J,WUEN B Y E,et al.Analysis of shape of short-tailed Hulun Buir sheep[J].China Herbivores,2006(S1):148-149. (in Chinese)
[23] XU S S,REN X,YANG G L,et al.Genome-wide association analysis identifies the genetic basis of fat deposition in the tails of sheep (Ovis aries)[J].Anim Genet,2017,48(5):560-569.
[24] SABIN M A,YAU S W,RUSSO V C,et al.Dietary monounsaturated fat in early life regulates IGFBP2:implications for fat mass accretion and insulin sensitivity[J].Obesity,2011,19(12):2374-2381.
[25] 杨华,徐珍,左波.猪IGFBP2基因多态性及其与胴体、肉质性状的关联分析[J].中国畜牧杂志,2017,53(3):25-28.
YANG H,XU Z,ZUO B.Polymorphism of IGFBP2 gene and its association with carcass and meat quality traits in pigs[J].Chinese Journal of Animal Science,2017,53(3):25-28. (in Chinese)
[26] GENG T Y,SUTTER A,HARLAND M D,et al.SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes[J].J Lipid Res,2015,56(12):2359-2371.
[27] LIU Z J,GAN L,LIU G N,et al.Sirt1 decreased adipose inflammation by interacting with Akt2 and inhibiting mTOR/S6K1 pathway in mice[J].J Lipid Res,2016,57(8):1373-1381.
[28] OTIENO C J,BASTIAANSEN J,RAMOS A M,et al.Mapping and association studies of diabetes related genes in the pig[J].Anim Genet,2005,36(1):36-42.
[29] MIAO Z,ZHU F,ZHANG H,et al.Developmental patterns of FASN and LIPE mRNA expression in adipose tissue of growing Jinhua and Landrace gilts[J].Czech J Anim Sci,2010,55(12):557-564.
[30] ZHOU S L,LI M Z,LI Q H,et al.Differential expression analysis of porcine MDH1,MDH2 and ME1 genes in adipose tissues[J].Genet Mol Res,2012,11(2):1254-1259.
[31] CLARK D L.Transcription profiles of differentially marbled beef cattle[D].Champaign:University of Illinois at Urbana-Champaign,2008.
[32] LING C,HELLGREN G,GEBRE-MEDHIN M,et al.Prolactin (PRL) receptor gene expression in mouse adipose tissue:increases during lactation and in PRL-transgenic mice[J].Endocrinology,2000,141(10):3564-3572.
[33] LING C,SVENSSON L,ODÉN B,et al.Identification of functional prolactin (PRL) receptor gene expression:PRL inhibits lipoprotein lipase activity in human white adipose tissue[J].J Clin Endocrinol Metab,2003,88(4):1804-1808.
[34] AUBERT J,CHAMPIGNY O,SAINT-MARC P,et al.Up-regulation of UCP-2 gene expression by PPAR agonists in preadipose and adipose cells[J].Biochem Biophys Res Commun,1997,238(2):606-611.
[35] ESTERBAUER H,SCHNEITLER C,OBERKOFLER H,et al.A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans[J].Nat Genet,2001,28(2):178-183.
[36] PEDERSEN S B,BRUUN J M,KRISTENSEN K,et al.Regulation of UCP1,UCP2,and UCP3 mRNA expression in brown adipose tissue,white adipose tissue,and skeletal muscle in rats by estrogen[J].Biochem Biophys Res Commun,2001,288(1):191-197.
[37] RICQUIER D,BOUILLAUD F.The uncoupling protein homologues:UCP1,UCP2,UCP3,StUCP and AtUCP[J].Biochem J,2000,345(2):161-179.
[38] HO P C,CHUANG Y S,HUNG C H,et al.Cytoplasmic receptor-interacting protein 140(RIP140) interacts with perilipin to regulate lipolysis[J].Cell Signalling,2011,23(8):1396-1403.
[39] HOCHBERG I,TRAN Q T,BARKAN A L,et al.Gene expression signature in adipose tissue of acromegaly patients[J].PLoS One,2015,10(6):e0129359.
[40] LEONARDSSON G,STEEL J H,CHRISTIAN M,et al.Nuclear receptor corepressor RIP140 regulates fat accumulation[J].Proc Natl Acad Sci U S A,2004,101(22):8437-8442.
[41] MERUVU S,HUGENDUBLER L,MUELLER E.Regulation of adipocyte differentiation by the zinc finger protein ZNF638[J].J Biol Chem,2011,286(30):26516-26523.
[42] CHEN T R,WANG P,CARROLL L K,et al.Generation and characterization of Tmeff2 mutant mice[J].Biochem Biophys Res Commun,2012,425(2):189-194.
[43] OSUMI T,HASHIMOTO T.Acyl-CoA oxidase of rat liver:a new enzyme for fatty acid oxidation[J].Biochem Biophys Res Commun,1978,83(2):479-485.
[44] KARIM M F,YOSHIZAWA T,SOBUZ S U,et al.Sirtuin 7-dependent deacetylation of DDB1 regulates the expression of nuclear receptor TR4[J].Biochem Biophys Res Commun,2017,490(2):423-428.
[45] DUCOS E,VERGōS V,DE BERNONVILLE T D,et al.Remarkable evolutionary conservation of antiobesity ADIPOSE/WDTC1 homologs in animals and plants[J].Genetics,2017,207(1):153-162.
[46] CHANG Y C,CHIU Y F,HE C T,et al.Genome-wide linkage analysis and regional fine mapping identified variants in the RYR3 gene as a novel quantitative trait locus for circulating adiponectin in Chinese population[J].Medicine,2016,95(44):e5174.
[47] 徐晨希,王梦琦,朱小瑞,等.中国荷斯坦牛FADS2基因3'端SNP突变对乳中脂肪酸组成的影响[J].中国农业科学,2016,49(11):2194-2202.
XU C X,WANG M Q,ZHU X R,et al.Effects of SNPs in the 3' untranslated regions of FADS2 on the composition of fatty acids in milk of Chinese Holstein[J].Scientia Agricultura Sinica,2016,49(11):2194-2202. (in Chinese)
[48] BOSCHETTI E,BORDONI A,MELUZZI A,et al.Fatty acid composition of chicken breast meat is dependent on genotype-related variation of FADS1 and FADS2 gene expression and desaturating activity[J].Animal,2016,10(4):700-708.
[49] 丁珍,李响,吴义霞,等.FADS2基因rs174575多态性与乳汁多不饱和脂肪酸水平的关系研究[J].中国妇幼保健,2015,30(20):3464-3466.
DING Z,LI X,WU Y X,et al.Study on the relationship between rs174575 polymorphism of FADS2 gene and polyunsaturated fatty acids levels in breast milk[J].Maternal & Child Health Care of China,2015,30(20):3464-3466. (in Chinese)
[50] VAITTINEN M,MÄNNISTÖ V,KÄKELÄ P,et al.Interorgan cross talk between fatty acid metabolism,tissue inflammation,and FADS2 genotype in humans with obesity[J].Obesity,2017,25(3):545-552.
[51] VAITTINEN M,WALLE P,KUOSMANEN E,et al.FADS2 genotype regulates delta-6 desaturase activity and inflammation in human adipose tissue[J].J Lipid Res,2016,57(1):56-65.
[52] ENSENAUER R,HE M,WILLARD J M,et al.Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial β-oxidation of unsaturated fatty acids[J].J Biol Chem,2005,280(37):32309-32316.
[53] KUWABARA W M T,PANVELOSKI-COSTA A C,YOKOTA C N F,et al.Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats:Are they reliable models to study Type 2 Diabetes mellitus?[J].PLoS One,2017,12(12):e0189622.
[54] HUH J Y,PARK J,KIM J I,et al.Deletion of CD1d in adipocytes aggravates adipose tissue inflammation and insulin resistance in obesity[J].Diabetes,2017,66(4):835-847.
[55] ZHANG H,XUE R,ZHU S,et al.M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue[J].Cell Mol Immunol,2017,doi:10.1038/cmi.2017.11.
[56] MA Z S,SONG Z Y,ZHANG Q.Cholesterol efflux is LXRα isoform-dependent in human macrophages[J].BMC Cardiovasc Disord,2014,14:80.
[57] LANG J K,CIMATO T R.Cholesterol and hematopoietic stem cells:inflammatory mediators of atherosclerosis[J].Stem Cell Transl Med,2014,3(5):549-552.
[58] BATES S R,TAO J Q,COLLINS H L,et al.Pulmonary abnormalities due to ABCA1 deficiency in mice[J].Am J Physiol Lung Cell Mol Physiol,2005,289(6):L980-L989.
[59] EDGEL K A,MCMILLEN T S,WEI H,et al.Obesity and weight loss result in increased adipose tissue ABCG1 expression in db/db mice[J].Biochim Biophys Acta,2012,1821(3):425-434.
[60] SPARTANO N L,LAMON-FAVA S,MATTHAN N R,et al.Regulation of ATP-binding cassette transporters and cholesterol efflux by glucose in primary human monocytes and murine bone marrow-derived macrophages[J].Exp Clin Endocrinol Diabetes,2014,122(8):463-468.
[61] CHEN J,MENG Y,ZHOU J,et al.Identifying candidate genes for Type 2 Diabetes Mellitus and obesity through gene expression profiling in multiple tissues or cells[J].J Diabetes Res,2013,2013:970435.
[62] RÖNN T,VOLKOV P,GILLBERG L,et al.Impact of age,BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood[J].Hum Mol Genet,2015,24(13):3792-3813.
[63] KULZER J R,STITZEL M L,MORKEN M A,et al.A common functional regulatory variant at a Type 2 diabetes locus upregulates ARAP1 expression in the pancreatic beta cell[J].Am J Hum Genet,2014,94(2):186-197.