猪胴体性状全基因组关联分析及背膘厚主效基因筛选研究
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摘要
本研究从基因组水平对猪的重要且复杂的经济性状-胴体性状研究，并筛选背膘厚性状的主效候选基因。本研究构建了大白猪×民猪F2代资源群体，对其应用Illumina Porcine SNP60K BeadChip基因分型，之后对猪的胴体性状进行了全基因组关联分析（Genome-wideAssociation Study, GWAS），并对背膘厚性状的显著区间深入研究筛选主效候选基因。
1、对F2资源群体的头重、蹄重、板油重、背膘厚、胴体长、胴体重和屠宰体重七个性状进行描述分析，均值分别为7.52kg,1.69kg,1.46kg,3.84cm,95.58cm,78.96kg and109.11kg。
2、根据GRAMMAR-GC (Genome-wide Rapid Association using the Mixed Model andRegression-Genomic Control)计算方法，应用R语言环境下GenABEL软件包和DMU软件对F2资源群体个体的头重、蹄重、板油重、背膘厚、胴体长、胴体重和屠宰体重7个性状进行全基因组关联分析。结果显示除胴体重外，其余6个指标均检测到了全基因组水平显著相关的SNP位点（P <1.03E–06），显著位点个数分别为头重63个、蹄重84个、板油重56个、屠宰体重8个、胴体长78个及背膘厚35个。这些显著位点均位于7号染色体上，几乎全部聚集于31Mb到49Mb范围内。
3、通过单倍型分析、选择性清除分析方法对背膘厚GWAS显著区间进一步分析，将显著区间缩小至0.50Mb（34755605-35332315）区段，该区域内含有六个已有注释的基因（HMGA1、GRM4、NUDT3、RPS10、SPDEF和PACSIN1）。对这6个基因在两个试验群体（60d/150d/210d民猪、大白猪试验群体和60d二花脸猪、大白猪试验群体）背膘组织中进行荧光定量PCR分析，发现只有HMGA1mRNA有显著性的表达差异（P<0.05）。因此，HMGA1被确定为猪背膘厚的主效候选基因。
4、对小鼠3T3-L1前体脂肪细胞系HMGA1基因进行了RNAi试验，对转染了siRNA的细胞和阴性对照细胞诱导分化后进行荧光定量试验，结果显示干扰后，HMGA1、C/EBP-β和PPARγ基因的mRNA表达量都显著下调（P<0.05）。此结果也说明了HMGA1在3T3-L1前体脂肪细胞分化为脂肪细胞的过程中发挥作用。
This study analyzed the carcass traits from the genome level and the backfat trait was study indepth to screen the major candidate gene. The Large White×MinZhu F2resource group wasestablished and Genome-Wide Association Study (GWAS) was carried out using Illumina PorcineSNP60K DNA Chip for pig carcass traits. Then a significant area of backfat trait was in-depthanalyzed to screen major candidate gene. Research contents are as follows:
1. The seven carcass traits containing head weight (HT), feet weight (FT), leaf fat weight (LFW),carcass length (CL), carcass weight (CW), backfat thickness (BFT) and slaughter body weight(SBW) were determined and described.
2. According to the GRAMMAR-GC (Genome-wide Rapid Association using the Mixed Modeland Regression-Genomic Control) calculation method, GWAS were performed for HT, FT,LFW, CL, CW, BFT and SBW by using GenABEL under R-language environment and DMUsoftware in F2individual. The results showed the significant SNPs (P <1.03E–06) weredetected for six indexes, except of CW. The number of significant SNPs for HT, FT, LFW, CL,BFT and SBW were63,84,56,78,35and8respectively. All the significant SNPs werelocated on chromosome7and almost all were gathered in the31Mb to49Mb range,narrowing QTL range of carcass traits.
3. The significant range of backfat trait was narrowed and located on chromosome70.50Mb(34755605-35332315) by haplotype analysis, selective sweep and P<0.01leve significantSNPs by GWAS. The narrowed range was blasted in Ensembl then six gene (HMGA1、GRM4、NUDT3、RPS10、SPDEF and PACSIN1), which have been annotated, were obtained.The fluorescence quantitative PCR for six genes were tested in backfat tissue of twoexperimental groups (60d/150d/210d old MinZhu and Large White pig test groups and60dold Erhualian pig and Large White pig test groups). The results showed HMGA1mRNA wasonly detected significant different expression. Therefore, HMGA1was identified as the majorcandidate for porcine backfat thickness.
4. The RNAi test of HMGA1gene was performed on mouse3T3-L1preadipocyte cell lines.After induced differentiation for RNAi cells and negative control cells, cells were collectedand genes were tested by fluorescence quantitative PCR. Results showed that after interference, the mRNA expression of HMGA1、C/EBP-βand PPARγwere all significantlylowered (P<0.05). The results also showed that HMAG1played a role in3T3-L1preadipocytedifferentiating to adipocyte.
1、对F2资源群体的头重、蹄重、板油重、背膘厚、胴体长、胴体重和屠宰体重七个性状进行描述分析，均值分别为7.52kg,1.69kg,1.46kg,3.84cm,95.58cm,78.96kg and109.11kg。
2、根据GRAMMAR-GC (Genome-wide Rapid Association using the Mixed Model andRegression-Genomic Control)计算方法，应用R语言环境下GenABEL软件包和DMU软件对F2资源群体个体的头重、蹄重、板油重、背膘厚、胴体长、胴体重和屠宰体重7个性状进行全基因组关联分析。结果显示除胴体重外，其余6个指标均检测到了全基因组水平显著相关的SNP位点（P <1.03E–06），显著位点个数分别为头重63个、蹄重84个、板油重56个、屠宰体重8个、胴体长78个及背膘厚35个。这些显著位点均位于7号染色体上，几乎全部聚集于31Mb到49Mb范围内。
3、通过单倍型分析、选择性清除分析方法对背膘厚GWAS显著区间进一步分析，将显著区间缩小至0.50Mb（34755605-35332315）区段，该区域内含有六个已有注释的基因（HMGA1、GRM4、NUDT3、RPS10、SPDEF和PACSIN1）。对这6个基因在两个试验群体（60d/150d/210d民猪、大白猪试验群体和60d二花脸猪、大白猪试验群体）背膘组织中进行荧光定量PCR分析，发现只有HMGA1mRNA有显著性的表达差异（P<0.05）。因此，HMGA1被确定为猪背膘厚的主效候选基因。
4、对小鼠3T3-L1前体脂肪细胞系HMGA1基因进行了RNAi试验，对转染了siRNA的细胞和阴性对照细胞诱导分化后进行荧光定量试验，结果显示干扰后，HMGA1、C/EBP-β和PPARγ基因的mRNA表达量都显著下调（P<0.05）。此结果也说明了HMGA1在3T3-L1前体脂肪细胞分化为脂肪细胞的过程中发挥作用。
This study analyzed the carcass traits from the genome level and the backfat trait was study indepth to screen the major candidate gene. The Large White×MinZhu F2resource group wasestablished and Genome-Wide Association Study (GWAS) was carried out using Illumina PorcineSNP60K DNA Chip for pig carcass traits. Then a significant area of backfat trait was in-depthanalyzed to screen major candidate gene. Research contents are as follows:
1. The seven carcass traits containing head weight (HT), feet weight (FT), leaf fat weight (LFW),carcass length (CL), carcass weight (CW), backfat thickness (BFT) and slaughter body weight(SBW) were determined and described.
2. According to the GRAMMAR-GC (Genome-wide Rapid Association using the Mixed Modeland Regression-Genomic Control) calculation method, GWAS were performed for HT, FT,LFW, CL, CW, BFT and SBW by using GenABEL under R-language environment and DMUsoftware in F2individual. The results showed the significant SNPs (P <1.03E–06) weredetected for six indexes, except of CW. The number of significant SNPs for HT, FT, LFW, CL,BFT and SBW were63,84,56,78,35and8respectively. All the significant SNPs werelocated on chromosome7and almost all were gathered in the31Mb to49Mb range,narrowing QTL range of carcass traits.
3. The significant range of backfat trait was narrowed and located on chromosome70.50Mb(34755605-35332315) by haplotype analysis, selective sweep and P<0.01leve significantSNPs by GWAS. The narrowed range was blasted in Ensembl then six gene (HMGA1、GRM4、NUDT3、RPS10、SPDEF and PACSIN1), which have been annotated, were obtained.The fluorescence quantitative PCR for six genes were tested in backfat tissue of twoexperimental groups (60d/150d/210d old MinZhu and Large White pig test groups and60dold Erhualian pig and Large White pig test groups). The results showed HMGA1mRNA wasonly detected significant different expression. Therefore, HMGA1was identified as the majorcandidate for porcine backfat thickness.
4. The RNAi test of HMGA1gene was performed on mouse3T3-L1preadipocyte cell lines.After induced differentiation for RNAi cells and negative control cells, cells were collectedand genes were tested by fluorescence quantitative PCR. Results showed that after interference, the mRNA expression of HMGA1、C/EBP-βand PPARγwere all significantlylowered (P<0.05). The results also showed that HMAG1played a role in3T3-L1preadipocytedifferentiating to adipocyte.
引文
1.李方华、候玲玲，苏晓华，郑扬，庞全海，关伟军，马月辉。RNA干扰的研究进展及应用。生物技术通讯，2010；21:740-745.
2.蔡教英，刘姚，王文君，杨武英。3T3-L1前体脂肪细胞在功能性成分评价中的应用。食品科学。2011,32：301-305.
3.庞卫军，李影，卢荣华等。脂肪细胞分化过程中的分子时间。细胞生物学杂志，2005,27(5):497-500.
4.智联腾，周钢桥，贺福初.人类复杂疾病关联研究中群体分层的检出和校正.遗传,2007,29(1):3-7.
5.王继英,王海霞,迟瑞宾,郭建凤,武英.全基因组关联分析在畜禽中的研究进展.中国农业科学.2013,46(4):819-829.
6. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab2000;11:327-32.
7. Ahima RS, Kelly J, Elmquist JK, Flier JS. Distinct physiologic and neuronal responses todecreased leptin and mild hyperleptinemia. Endocrinology,1999,140:4923-32.
8. Amin N, van Duijn CM, Aulchenko YS. A genomic background based method for associationanalysis in related individuals. PLoS One.2007:2:e1274.
9. Anne-Sophie Van Laere, Minh Nguyen, Martin Braunschweig, Carine Nezer, CatherineCollette, et al. A regulatory mutation in IGF2causes a major QTL effect on muscle growth inthe pig. Nature.2003,425(6960):832-836.
10. Aulchenko YS, de Koning DJ, Haley C. Genomewide rapid association using mixed modeland regression: a fast and simple method for genomewide pedigree-based quantitative traitloci association analysis. Genetics.2007,177:577-585.
11. Bacanu SA, Devlin B, Roeder K. The power of genomic control. Am J Hum Genet.2000,66(6):1933-44.
12. Barak Y, Nelson M C, Ong E S,et al. PPARy is required for placental, cardiac, and adiposetissue development. Mol Cell,1999,4:585-595.
13. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD andhaplotype maps. Bioinformatics.2005,21(2):263-5.
14. Bernstein E, Caudy A A, Hammond S M, et al. Role for a bidentate ribonuclease in theinitiation step of RNA interference. Nature,2001,409(6818):363-366.
15. Boddicker N1, Waide EH, Rowland RR, Lunney JK, Garrick DJ, Reecy JM, Dekkers JC.Evidence for a major QTL associated with host response to porcine reproductive andrespiratory syndrome virus challenge. J Anim Sci.2012Jun;90(6):1733-46.
16. Brun RP, Spiegelman BM. PPAR gamma and the molecular control of adipogenesis [J]. JEndocrinol,1997,155:217-8.
17. Cardon LR, Palmer LJ. Population stratification and spurious allelic association. Lancent.2003,361(9357):598-604.
18. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, et al. Replicatinggenotype-phenotype associations. Nature.2007,447(7145):655~60.
19. Chardon P, Renard C, Gaillard CR, Vaiman M (2000) The porcine major histocompatibilitycomplex and related paralogous regions: a review. Genet Sel Evol32(2):109-28.
20. Chawla A, Schwarz E J, et al. Peroxisome proliferator-activated receptor (PPAR) gamma:adipose-predominant expression and induction early in adipocyte differentiation[J].Endocrinology,1994,135(2):798-800.
21. Chiappetta G, Avantaggiato V, Visconti R, Fedele M, Battista S, et al.(1996) High levelexpression of the HMGI(Y) gene during embryonic development. Oncogene.13(11):2439-46.
22. Cho IC, Park HB, Yoo CK, Lee GJ, Lim HT,et al.. QTL analysis of white blood cell, plateletand red blood cell-related traits in an F2intercross between Landrace and Korean native pigs.Anim Genet2011,42:621-626.
23. Christopher I.A. Successful dedign and conduct of genome-wide association studies.HumanMolecular Genetics.2007,16(Review issue2):R220-R225.
24. Chung J, Tsai S, James AH, Thames BH, Shytle S, et al.(2012) Lack of genomic imprintingof DNA primase, polypeptide2(PRIM2) in human term placenta and white blood cells.Epigenetics7(5):429-31.
25. Clark AG. Inference of haplotypes from PCR-amplified samples of diploid populations. MolBiol Evol.1990,7(2):111-22.
26. Clemens JC1, Worby CA, Simonson-Leff N, Muda M, Maehama T, Hemmings BA, DixonJE. Use of double-stranded RNA interference in Drosophila cell lines to dissect signaltransduction pathways. Proc Natl Acad Sci U S A.2000,97(12):6499-503
27. Cleynen I, Van de Ven WJ.(2008) The HMGA proteins: a myriad of functions (Review). Int JOncol.32(2):289-305.
28. Cleynen I, Van de Ven WJ. The HMGA proteins: a myriad of functions. Int J Oncol,2008,32(2):289-305.
29. Demeure O, Sanchez MP, Riguet J, Iannuccelli N, Demars J, et al.(2005) Exclusion of theswine leukocyte antigens as candidate region and reduction of the position interval for theSus scrofa chromosome7QTL affecting growth and fatness. J Anim Sci83(9):1979-87.
30. Dowell NL, Mason MJ, Johnson PC, et al. Chromatin-dependent binding of the ScerevisiaeHMGB protein Nhp6A affects nucleosome dynamics and transcription. Genes Dev,2010,24(18)：2031-2042.
31. Dreyer C, Krey Q Keller F, et al. Control of the peroxisomal beta-oxidation pathway by anovel family of nuclear hormone receptors. Cell,1992,68:879?887
32. Duijvesteijn N, Knol EF, Merks JW, Crooijmans RP, Groenen MA, Bovenhuis H, Harliziue B.A genome-wide association study on androstenone levels in pigs reveals a cluster ofcandidate genes on chromosome6. BMC Genet.2010,11:42.
33. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Wdber K, Tuschl T. Duplexes of21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature,2011;411(6836):494-8
34. Evans A, Lennard T W, Davies B R. High-mobility group protein1(Y): metastas isassociated or metastas is inducing. J Surg Oncol.2004,88(2):86-99.
35. Evans RM, Barish GD, Wang YX (2004) PPARs and the complex journey to obesity. NatMed10(4):355-61.
36. Evans RM. The steroid and thyroid hormone receptor superfamily[J]. Science,1988,240:889-895.
37. Excoffier L, Slatkin M. Maximum-likelihood estimation of molecular haplotype frequenciesin a diploid population. Mol Biol Evol.1995,12(5):921-7.
38. Fan B, Onteru SK, Du ZQ, Garrick DJ, Stalder KJ, Rothschild MF. Genome-wide associationstudy identifies loci for body composition and structural soundness traits in pigs. PLoS One.2011,6(2):e14726
39. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference bydouble-stranded RNA in Caenorhabditis elegans. Nature.1998,391(6669):806-11.
40. Foti D, Chiefari E, Fedele M, et al. Lack of the architectural factor HMGA1causes insulinresistance and diabetes in humans and mice. Nat Med,2005,11:765-773.
41. Fu WX1, Liu Y, Lu X, Niu XY, Ding XD, Liu JF, Zhang Q. A genome-wide association studyidentifies two novel promising candidate genes affecting Escherichia coli F4ab/F4acsusceptibility in swine. PLoS One.2012;7(3):e32127.
42. Gilbert H, LE Roy P, Milan D, Bidanel JP (2007) Linked and pleiotropic QTLs influencingcarcass composition traits detected on porcine chromosome7. Genet Res89(2):65-72.
43. Goodwin GH, Nicolas RH, Jones EW. An improved large scale fractionation of high mobilitygroup non-histone chromatin proteins. Biochim Biophys Acta.1975,405(2):280-91.
44. Green H, Kehinde O. Spontaneous heritable changes leading to increased adipocyteconversion in3T3cells. Cell,1976,7(1):105.
45. Gregoire FM, Smas CM, Sul HS.Understanding adipocyte differentiation. Physiol Rev,1998,78:783-809,
46. Guo X, Liao K. Analysis of gene expression profile during3T3-L1preadipocytedifferentiation. Gene,2000,251:45-53.
47. Hao K, Li C, Rosenow C, Wong WH. Detect and adjust for population stratification inpopulation-based association study using genomic control markers: an application ofAffymetrix Genechip Human Mapping10K array. Eur J Hum Gent.2004,12(12):1001-6.
48. Hayes BJ, Bowman PJ, Chamberlain AJ, Savin K, van Tassell CP, Sonstegard TS, GoddardME. A validated genome wide association study to breed cattle adapted to an environmentaltered by climate change. PLoS One2009,4:e6676.
49. Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases andcomplex traits. Nat Rev Genet2005,6(2):95-108.
50. Holst D, Grimaldi PA. New factors in the regulation of adipose differentiation andmetabolism [J]. Curr Opin Lipidol,2002,13:241-5.
51. Hoover RN. The evolution of epidemiologic research. Epidemiology.2007,18(1):13-17
52. Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method forthe next generation of genome-wide association studies. PLoS Genet.2009,5(6): e1000529.
53. Hristov A, Cope L, Di Cello F, Reyes MD, Singh M, et al.(2010) HMGA1correlates withadvanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma. ModPathol.23:98-104.
54. Huang W, Kirkpatrick BW, Rosa GJ, Khatib H. A genome-wide association study usingselective DNA pooling identifies candidate markers for fertility in Holstein cattle. AnimGenet2010,41:570-578.
55. Jiang L, Liu J, Sun D, Ma P, Ding X, Yu Y, Zhang Q. Genome wide association studies formilk production traits in Chinese Holstein population. PLoS One.2010,5(10):e13661.
56. John C, Katalin K, Drew W, et al. Inhibition of HIV-1infection by small interferingRNA-mediated RNA interference. Immounal,2002,169(9):5196.
57. Joost HG, Schurmann A. Subcellular fractionation of adipocytes and3T3-L1cells.MethodsMol Biol,2001,155:77
58. Kim M S, Yoon C Y, Jang PG, et al. The mitogenic and antiapoptotic actions of ghrelin in3T3-L1adipocytes. Molecular Endocrinology,2004,18(9):2291-2301.
59. Klein RJ, Zeiss C, Chew EY, et al. Complements factor H polymorphism in age-relatedmacular degeneration. Science.2005,308(5720):385-389.
60. Knol JC, Pham TV, Meijer GA, et al. Subnuclear proteomics in colorectal cancer:identification of proteins enriched in the nuclear matrix fraction and regulation in adenoma tocarcinoma progression. Mol Cell Protemics,2010,9(15):998-1005.
61. Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting andreporting linkage results. Nat Genet.1995,11(3):241-7.
62. Lane MD, Lin FT, MacDougald OA, et al. Control of adipocyte differentiation byCCAAT/enhancer-binding protein alpha (C/EBP alpha). Int J Obes Relat Metab Disord.1996,3:S91-6.
63. Lee CH, Olson P, Hevener A, Mehll, Chong LW, et al.(2006) PPARdelta regulates glucosemetabolism and insulin sensitivity. Proc Natl Acad Sci U S A103(9):3444-9.
64. Lee N S, Bauer G, Rossi J. Expression of small interfering RNA star geted against HIV-1revtranscripts in human cells. Nat Biotechnol,2002,20(5):500-505.
65. Lemberger T, Desvergne B,Wahli W. Peroxisome proliferator-activated receptors: A
66. Li H, Li WX, Ding SW. Induction and suppression of RNA silencing by an animal virus.Science.2002;296(5571):1319-21.
67. Lin FT, Lane MD. CCAAT/enhancer-binding protein alpha is sufficient to initiate the3T3-L1adipocyte differentiation program. Proc Natl Acad Sci USA.1994,91(19):8757-61.
68. Lin S, Cutler DJ, Zwick ME, Chakravarti A. Haplotype inference in random populationsamples. Am J Hum Genet.2002,71(5):1129-37.
69. Liu R, Sun Y, Zhao G, Wang F, Wu D, et al.(2013) Genome-wide association study identifiesLoci and candidate genes for body composition and meat quality traits in Beijing-Youchickens. PLoS One8(4): e61172.
70. Luo W, Chen S, Cheng D, Wang L, Li Y,et al.. Genome-wide association study of porcinehematological parameters in a Large White×Minzhu F2resource population.Int J Biol Sci2012,8:870-881.
71. Luo W, Cheng D, Chen S, Wang L, Li Y,et al.. Genome-wide association analysis of meatquality traits in a porcine Large White×Minzhu intercross population.Int J Biol Sci2012,8:580-595.
72. Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, et al.(2003) Peroxisomeproliferator-activated receptor delta controls muscle development and oxidative capability.FASEB J17(15):2299-301.
73. Ma J, Ren J, Guo Y, Duan Y, Ding N, et al.(2009) Genome-wide identification ofquantitative trait loci for carcass composition and meat quality in a large-scale White Duroc×Chinese Erhualian resource population. Anim Genet40(5):637-47.
74. Ma J, Yang J, Zhou L, Zhang Z, Ma H, et al.(2013) Genome-wide association study of meatquality traits in a white duroc×erhualian f2intercross and chinese sutai pigs. PLoS One8:e64047.
75. MacDougald OA, Lane MD. Transcriptional regulation of gene expression during adipocytedifferentiation. Annu Rev Biochem.1995,64:345-73.
76. Madsen P, Sorensen P, Su G, Damgaard LH, Thomsen H, Labouriau R. DMU-a package foranalyzing multivariate mixed models. In8thWorld Congress on Genetics Applied toLivestock Production. Brasil,2006.
77. Mai MD, Sahana G, Christiansen FB, Guldbrandtsen B: A genome-wide association study formilk production traits in Danish Jersey cattle using a50K single nucleotide polymorphismchip. J AnimSci2010,88:3522-3528.
78. Martin ER, Monks SA, Warren LL, Kaplan NL. A test for linkage and association in generalpedigres: the pedigree disequilibrium test. Am J Hum Genet.2000,67(1):146-54.
79. McCarthy MI, Hirschhorn JN. Genome-wide association studies: potential next steps on agenetic journey. Hum Mol Genet,2008,17:156-165.
80. Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature,2004,431(7006):343-349.
81. Melillo RM, Pierantoni G, Scala S, Battista S, Fedele M, et al.(2001) Critical role of theHMGI(Y) proteins in adipocytic cell growth and differentiation. Mol Cell Biol.21(7):2485-95.
82. Milan D, Bidanel JP, Iannuccelli N, Riguet J, Amigues Y, et al.(2002) Detection ofquantitative trait loci for carcass composition traits in pigs. Genet Sel Evol34(6):705-28.
83. Minozzi G, Buggiotti L, Stella A, Strozzi F, Liuni M, Williams JL. Genetic loci involved inantibody response to Mycobacterium avium ssp. paratuberculosisi in cattle. PLoS One.2010,5(6):e11117.
84. Morris RW, Kaplan NL. On the advantage of haplotype analysis in the presence of multipledisease susceptibility allels. Genet Epidemiol.2002,23(3):221-33.
85. Murdoch BM, Murdoch GK, Settles M, McKay S, Williams JL, Moore SS. Genome-widescan identifies loci associated with classical BSE occurrence. PLoS One2011,6(11):e26819.
86. Nielsen R. Molecular signatures of natural selection. Annual Review of Genetics.2005,39:197-218.
87. Niu T, Qin ZS, Xu X, Liu JS. Bayesian haplotype inference for multiple linkedsingle-nucleotide polymorphisms. Am J Hum Genet.2002,70(1):157-69.
88. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression [J]. J Nutr,2000,130:3122S-3126S.
89. Osiecka B, Zougman A, Wisniewski JR, et al. Immunohistochemical and proteomicevaluation of nuclear ubiquitous casein and cyclin-dependent kinases substrate in invasiveductal carcinoma of the breast. J Biomed Biotechol,2009:919645.
90. Philippe L, Giulia C,Fruchart JC, et al. Sorting out the Roles of PPARa in Energymetabolism and vascular homeostasis, J Clin Invest,2006,116(3):571-580.
91. Pierantoni GM, Battista S, Pentimalli F, Fedele M, Visone R et al. A truncated HMGA1geneinduces proliferation of the3T3-L1pre-adipocytic cells: a model of human lippomas.
92. Poulos S P, Dodson M V, Hausman G J. Cell line models for differentiation: preadipocytesand adipocytes. Experimental Biology and Medicine.2010,235(10):1185-1193.
93. Rangwala SM, Lazar MA. Transcriptional control of adipogenesis [J]. Annu Rev Nutr,2000,20:535-59.
94. Reeves R. Nuclear functions of the HMG proteins. Biochim Biophys Acta.2010,1799(1-2):3-14.
95. Ren J, Duan Y, Qiao R, Yao F, Zhang Z, et al.(2011) A missense mutation in PPARD causes amajor QTL effect on ear size in pigs. PLoS Genet7(5): e1002043.
96. Ren J, Mao H, Zhang Z, Xiao S, Ding N, Huang L. A6-bp deletion in the TYRP1genecauses the brown colouration phenotype in Chinese indigenous pigs. Heredity2011,106:862-868.
97. Reynolds A, Leake D, Boese Q, et al. Rational siRNA design for RNA interference. NatBiotechnol.2004,22(3):326-30.
98. Rosen E D, Sarraf P, Troy A E, et al. PPARg Is Required for the Differentiation of AdiposeTissue In Vivo and In Vitro. Mol Cell,1999,4:611-617.
99. Rubinson D A, Dillon C P, Kwiatkowski A V, et al. A lentivirus-based system to functionallysilence genes in primary mammalian cells, stem cells and transgenic mice by RNAinterference. Nat Genet,2003,33:401-406.
100. Samani NJ, Erdmann J, Hall AS, et al. Genome-wide association analysis of coronary arterydisease. New Engl J Med.2007,357(5):443-453.
101. Sanchez MP, Riquet J, Iannuccelli N, Gogue J, Billon Y, et al.(2006) Effects of quantitativetrait loci on chromosomes1,2,4, and7on growth, carcass, and meat quality traits inbackcross Meishan×Large White pigs. J Anim Sci84(3):526-37.
102. Scherr M, Morgan MA, Eder M. Gene silencing mediated by small interfering RNAs inmammalian cells. Curt Med Chem.2003,10:245-256.
103. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator activated receptor(PPAR) in mediating the effects of fibrates and fatty acids on gene expression,J Lip Res,1996,37:907-925.
104. Schoonjans, K., Staels, B., and Auwerx J. The peroxisomal proliferator activated receptors(PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim.Biophys. Acta1996,1302:93–109.
105. Schopen GC, Visker MH, Koks PD, Mullaart E, van Arendonk JA, Bovenhuis H.Whole-genome association study for milk protein composition in dairy cattle. J Dairy Sci2011,94:3148-3158.
106. Scuteri A, Sanna S, Chen W, et al. Genome-wide association scan shows genetic variants inthe FTO gene are association with obesity-related traits. PLoS Genetics.2007,3(7):1200-1210.
107. Sgarra R, Lee J, Tessari M A, et al. The AT-hook of the chromatin architectural transcriptionfactor high mobility group A1a is arginine-methylated by protein arginine methyltransferase6. J Biol Chem,2006,281(7):3764-3772.
108. Shah SN, Cope L, Poh W, Belton A, Roy S, et al.(2013) HMGA1: a master regulator oftumor progression in triple-negative breast cancer cells. PLoS One.8(5): e63419.
109. Sijen T, Vijn I, Rebocho A, et al. Transcriptional and posttranscriptional gene silencing aremechanistically related. Curr Biol.2001,11(6):434-40.
110. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Optimal designs for two-stage genome-wideassociation studies. Genet Epidemiol.2007,31(7):776-788.
111. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A,Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV,Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P. A genome-wideassociation study identifies novel risk loci for type2diabetes. Nature2007,445(7130):881-5.
112. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstructionfrom population data. Am J Hum Genet.2001,68(4):978-89.
113. Sui G H, Soohoo C, Shi Y, et al. A DNA vector-based RNAi technology to suppress geneexpression in mammalian cells. Pro Natl Acad Sci USA,2002;99(8):5515-5520.
114. Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, et al. A single IGF1allel is a majordeterminant of small size in dogs. Science.2007,316L:112-115.
115. Tanaka T, Yamamoto J, Iwasaki S, Asaba H, Hamura H, et al.(2003) Activation ofperoxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletalmuscle and attenuates metabolic syndrome. Proc Natl Acad Sci U S A100(26):15924-9.
116. Tang QQ, Otto TC, Lane MD. CCAAT/enhancer-binding protein beta is required for mitoticclonal expansion during adipogenesis. Proc Natl Acad Sci USA.2003,100(3):850-5.
117. Thomas AP, Teri A. How to interpret a Genome-wide Association Study. JAMA.2008;299(11):1335-1344.
118. Tijsterman M, Kitting RF, Plasterk RHA. The genetics of RNA silencing. Annu Rev Genet,2002,36:489-519.
119. Tsai Y S, Maeda N. PPARy: A critical determinant of body fat distribution in humans andmice. Trends Cardiovasc Med,2005,15:81-85.
120. Tuschl T. Expanding small RNA interference. Nature Biotechnology,2002,20:446-448.
121. Vidal-Puig A J, Considine R V, et al. Peroxisome proliferator activated receptor geneexpression in human tissue. Effects of obesity, weight loss and regulation by insulin andglucocorticoid. J Clin Invest,1997,99:2416-2422.
122. Vreeland WN, Meagher RJ, Barron AE. Multiplexed, high-throughput genotyping bysingle-base extension and end-labeled free-solution electrophoresis. Anal Chem.2002,74(17):4328-33.
123. Wang J, Jiang J, Fu W, Jiang L, Ding X,et al.. A genome-wide detection of copy numbervariations using SNP genotyping arrays in swine. BMC Genomics2012,13:273.
124. Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L. Anutrient-sensing pathway regulatesleptin gene expression in muscle and fat. Nature.1998,393:684-8.
125. Wang, N.D,Finegold M J, Bradley A, et al Impaired energy homeostasis in CEBP alphaknockout mice. Science,1995,269:1108—1112.
126. Wang WY, Barratt BJ, Clayton DG, Todd JA. Genome-wide association studies: theoreticaland practical concerns. Nat Rev Genet.2005,6(2):109-18.
127. Weiner BE, Huang H, Dattilo BM, Nilges MJ, Fanning E, et al.(2007) An iron-sulfur clusterin the C-terminal domain of the p58subunit of human DNA primase. J Biol Chem282(46):33444-51.
128. Xavier RJ and Rioux JD. Genome-wide association studies: a new window intoimmune-meidiated disease. Nature Revoews Immumology.2008,8:631-643.
129. Yang HY, Cheng CF, Djoko B, Lian WS, Tu CF, et al.(2007) Transgenic overexpression ofthe secreted, extracellular EGF-CUB domain-containing protein SCUBE3induces cardiachypertrophy in mice. Cardiovasc Res75(1):139-47.
130. Yang Q, Cui J, Chazaro I, et al. Power and type Ι error rate of false discovery rate approachesin genome-wide association studies. BMC Genet.2005,6(suppl1): S134.
131. Yeh WC, Cao Z, Classon M, et al. Cascade regulation of terminal adipocyte differentiation bythree members of the C/EBP family of leucine zipper proteins. Genes Dev.1995,9(2):168-81.
132. Youssef J, Badr M. Role of Peroxisome Proliferator-activated Receptors in InflammationControl. JBiomed biotechnol,2004,(3):156-166.
133. Zerbe LK, Kuchta RD (2002) The p58subunit of human DNA primase is important forprimer initiation, elongation, and counting. Biochemistry41(15):4891-900.
134. Zhong J, Chaerkady R, Kandasamy K, Gucek M, Cole RN, et al.(2011) The interactome of aPTB domain-containing adapter protein, Odin, revealed by SILAC. J Proteomics74(3):294-303.
2.蔡教英，刘姚，王文君，杨武英。3T3-L1前体脂肪细胞在功能性成分评价中的应用。食品科学。2011,32：301-305.
3.庞卫军，李影，卢荣华等。脂肪细胞分化过程中的分子时间。细胞生物学杂志，2005,27(5):497-500.
4.智联腾，周钢桥，贺福初.人类复杂疾病关联研究中群体分层的检出和校正.遗传,2007,29(1):3-7.
5.王继英,王海霞,迟瑞宾,郭建凤,武英.全基因组关联分析在畜禽中的研究进展.中国农业科学.2013,46(4):819-829.
6. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab2000;11:327-32.
7. Ahima RS, Kelly J, Elmquist JK, Flier JS. Distinct physiologic and neuronal responses todecreased leptin and mild hyperleptinemia. Endocrinology,1999,140:4923-32.
8. Amin N, van Duijn CM, Aulchenko YS. A genomic background based method for associationanalysis in related individuals. PLoS One.2007:2:e1274.
9. Anne-Sophie Van Laere, Minh Nguyen, Martin Braunschweig, Carine Nezer, CatherineCollette, et al. A regulatory mutation in IGF2causes a major QTL effect on muscle growth inthe pig. Nature.2003,425(6960):832-836.
10. Aulchenko YS, de Koning DJ, Haley C. Genomewide rapid association using mixed modeland regression: a fast and simple method for genomewide pedigree-based quantitative traitloci association analysis. Genetics.2007,177:577-585.
11. Bacanu SA, Devlin B, Roeder K. The power of genomic control. Am J Hum Genet.2000,66(6):1933-44.
12. Barak Y, Nelson M C, Ong E S,et al. PPARy is required for placental, cardiac, and adiposetissue development. Mol Cell,1999,4:585-595.
13. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD andhaplotype maps. Bioinformatics.2005,21(2):263-5.
14. Bernstein E, Caudy A A, Hammond S M, et al. Role for a bidentate ribonuclease in theinitiation step of RNA interference. Nature,2001,409(6818):363-366.
15. Boddicker N1, Waide EH, Rowland RR, Lunney JK, Garrick DJ, Reecy JM, Dekkers JC.Evidence for a major QTL associated with host response to porcine reproductive andrespiratory syndrome virus challenge. J Anim Sci.2012Jun;90(6):1733-46.
16. Brun RP, Spiegelman BM. PPAR gamma and the molecular control of adipogenesis [J]. JEndocrinol,1997,155:217-8.
17. Cardon LR, Palmer LJ. Population stratification and spurious allelic association. Lancent.2003,361(9357):598-604.
18. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, et al. Replicatinggenotype-phenotype associations. Nature.2007,447(7145):655~60.
19. Chardon P, Renard C, Gaillard CR, Vaiman M (2000) The porcine major histocompatibilitycomplex and related paralogous regions: a review. Genet Sel Evol32(2):109-28.
20. Chawla A, Schwarz E J, et al. Peroxisome proliferator-activated receptor (PPAR) gamma:adipose-predominant expression and induction early in adipocyte differentiation[J].Endocrinology,1994,135(2):798-800.
21. Chiappetta G, Avantaggiato V, Visconti R, Fedele M, Battista S, et al.(1996) High levelexpression of the HMGI(Y) gene during embryonic development. Oncogene.13(11):2439-46.
22. Cho IC, Park HB, Yoo CK, Lee GJ, Lim HT,et al.. QTL analysis of white blood cell, plateletand red blood cell-related traits in an F2intercross between Landrace and Korean native pigs.Anim Genet2011,42:621-626.
23. Christopher I.A. Successful dedign and conduct of genome-wide association studies.HumanMolecular Genetics.2007,16(Review issue2):R220-R225.
24. Chung J, Tsai S, James AH, Thames BH, Shytle S, et al.(2012) Lack of genomic imprintingof DNA primase, polypeptide2(PRIM2) in human term placenta and white blood cells.Epigenetics7(5):429-31.
25. Clark AG. Inference of haplotypes from PCR-amplified samples of diploid populations. MolBiol Evol.1990,7(2):111-22.
26. Clemens JC1, Worby CA, Simonson-Leff N, Muda M, Maehama T, Hemmings BA, DixonJE. Use of double-stranded RNA interference in Drosophila cell lines to dissect signaltransduction pathways. Proc Natl Acad Sci U S A.2000,97(12):6499-503
27. Cleynen I, Van de Ven WJ.(2008) The HMGA proteins: a myriad of functions (Review). Int JOncol.32(2):289-305.
28. Cleynen I, Van de Ven WJ. The HMGA proteins: a myriad of functions. Int J Oncol,2008,32(2):289-305.
29. Demeure O, Sanchez MP, Riguet J, Iannuccelli N, Demars J, et al.(2005) Exclusion of theswine leukocyte antigens as candidate region and reduction of the position interval for theSus scrofa chromosome7QTL affecting growth and fatness. J Anim Sci83(9):1979-87.
30. Dowell NL, Mason MJ, Johnson PC, et al. Chromatin-dependent binding of the ScerevisiaeHMGB protein Nhp6A affects nucleosome dynamics and transcription. Genes Dev,2010,24(18)：2031-2042.
31. Dreyer C, Krey Q Keller F, et al. Control of the peroxisomal beta-oxidation pathway by anovel family of nuclear hormone receptors. Cell,1992,68:879?887
32. Duijvesteijn N, Knol EF, Merks JW, Crooijmans RP, Groenen MA, Bovenhuis H, Harliziue B.A genome-wide association study on androstenone levels in pigs reveals a cluster ofcandidate genes on chromosome6. BMC Genet.2010,11:42.
33. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Wdber K, Tuschl T. Duplexes of21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature,2011;411(6836):494-8
34. Evans A, Lennard T W, Davies B R. High-mobility group protein1(Y): metastas isassociated or metastas is inducing. J Surg Oncol.2004,88(2):86-99.
35. Evans RM, Barish GD, Wang YX (2004) PPARs and the complex journey to obesity. NatMed10(4):355-61.
36. Evans RM. The steroid and thyroid hormone receptor superfamily[J]. Science,1988,240:889-895.
37. Excoffier L, Slatkin M. Maximum-likelihood estimation of molecular haplotype frequenciesin a diploid population. Mol Biol Evol.1995,12(5):921-7.
38. Fan B, Onteru SK, Du ZQ, Garrick DJ, Stalder KJ, Rothschild MF. Genome-wide associationstudy identifies loci for body composition and structural soundness traits in pigs. PLoS One.2011,6(2):e14726
39. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference bydouble-stranded RNA in Caenorhabditis elegans. Nature.1998,391(6669):806-11.
40. Foti D, Chiefari E, Fedele M, et al. Lack of the architectural factor HMGA1causes insulinresistance and diabetes in humans and mice. Nat Med,2005,11:765-773.
41. Fu WX1, Liu Y, Lu X, Niu XY, Ding XD, Liu JF, Zhang Q. A genome-wide association studyidentifies two novel promising candidate genes affecting Escherichia coli F4ab/F4acsusceptibility in swine. PLoS One.2012;7(3):e32127.
42. Gilbert H, LE Roy P, Milan D, Bidanel JP (2007) Linked and pleiotropic QTLs influencingcarcass composition traits detected on porcine chromosome7. Genet Res89(2):65-72.
43. Goodwin GH, Nicolas RH, Jones EW. An improved large scale fractionation of high mobilitygroup non-histone chromatin proteins. Biochim Biophys Acta.1975,405(2):280-91.
44. Green H, Kehinde O. Spontaneous heritable changes leading to increased adipocyteconversion in3T3cells. Cell,1976,7(1):105.
45. Gregoire FM, Smas CM, Sul HS.Understanding adipocyte differentiation. Physiol Rev,1998,78:783-809,
46. Guo X, Liao K. Analysis of gene expression profile during3T3-L1preadipocytedifferentiation. Gene,2000,251:45-53.
47. Hao K, Li C, Rosenow C, Wong WH. Detect and adjust for population stratification inpopulation-based association study using genomic control markers: an application ofAffymetrix Genechip Human Mapping10K array. Eur J Hum Gent.2004,12(12):1001-6.
48. Hayes BJ, Bowman PJ, Chamberlain AJ, Savin K, van Tassell CP, Sonstegard TS, GoddardME. A validated genome wide association study to breed cattle adapted to an environmentaltered by climate change. PLoS One2009,4:e6676.
49. Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases andcomplex traits. Nat Rev Genet2005,6(2):95-108.
50. Holst D, Grimaldi PA. New factors in the regulation of adipose differentiation andmetabolism [J]. Curr Opin Lipidol,2002,13:241-5.
51. Hoover RN. The evolution of epidemiologic research. Epidemiology.2007,18(1):13-17
52. Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method forthe next generation of genome-wide association studies. PLoS Genet.2009,5(6): e1000529.
53. Hristov A, Cope L, Di Cello F, Reyes MD, Singh M, et al.(2010) HMGA1correlates withadvanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma. ModPathol.23:98-104.
54. Huang W, Kirkpatrick BW, Rosa GJ, Khatib H. A genome-wide association study usingselective DNA pooling identifies candidate markers for fertility in Holstein cattle. AnimGenet2010,41:570-578.
55. Jiang L, Liu J, Sun D, Ma P, Ding X, Yu Y, Zhang Q. Genome wide association studies formilk production traits in Chinese Holstein population. PLoS One.2010,5(10):e13661.
56. John C, Katalin K, Drew W, et al. Inhibition of HIV-1infection by small interferingRNA-mediated RNA interference. Immounal,2002,169(9):5196.
57. Joost HG, Schurmann A. Subcellular fractionation of adipocytes and3T3-L1cells.MethodsMol Biol,2001,155:77
58. Kim M S, Yoon C Y, Jang PG, et al. The mitogenic and antiapoptotic actions of ghrelin in3T3-L1adipocytes. Molecular Endocrinology,2004,18(9):2291-2301.
59. Klein RJ, Zeiss C, Chew EY, et al. Complements factor H polymorphism in age-relatedmacular degeneration. Science.2005,308(5720):385-389.
60. Knol JC, Pham TV, Meijer GA, et al. Subnuclear proteomics in colorectal cancer:identification of proteins enriched in the nuclear matrix fraction and regulation in adenoma tocarcinoma progression. Mol Cell Protemics,2010,9(15):998-1005.
61. Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting andreporting linkage results. Nat Genet.1995,11(3):241-7.
62. Lane MD, Lin FT, MacDougald OA, et al. Control of adipocyte differentiation byCCAAT/enhancer-binding protein alpha (C/EBP alpha). Int J Obes Relat Metab Disord.1996,3:S91-6.
63. Lee CH, Olson P, Hevener A, Mehll, Chong LW, et al.(2006) PPARdelta regulates glucosemetabolism and insulin sensitivity. Proc Natl Acad Sci U S A103(9):3444-9.
64. Lee N S, Bauer G, Rossi J. Expression of small interfering RNA star geted against HIV-1revtranscripts in human cells. Nat Biotechnol,2002,20(5):500-505.
65. Lemberger T, Desvergne B,Wahli W. Peroxisome proliferator-activated receptors: A
66. Li H, Li WX, Ding SW. Induction and suppression of RNA silencing by an animal virus.Science.2002;296(5571):1319-21.
67. Lin FT, Lane MD. CCAAT/enhancer-binding protein alpha is sufficient to initiate the3T3-L1adipocyte differentiation program. Proc Natl Acad Sci USA.1994,91(19):8757-61.
68. Lin S, Cutler DJ, Zwick ME, Chakravarti A. Haplotype inference in random populationsamples. Am J Hum Genet.2002,71(5):1129-37.
69. Liu R, Sun Y, Zhao G, Wang F, Wu D, et al.(2013) Genome-wide association study identifiesLoci and candidate genes for body composition and meat quality traits in Beijing-Youchickens. PLoS One8(4): e61172.
70. Luo W, Chen S, Cheng D, Wang L, Li Y,et al.. Genome-wide association study of porcinehematological parameters in a Large White×Minzhu F2resource population.Int J Biol Sci2012,8:870-881.
71. Luo W, Cheng D, Chen S, Wang L, Li Y,et al.. Genome-wide association analysis of meatquality traits in a porcine Large White×Minzhu intercross population.Int J Biol Sci2012,8:580-595.
72. Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, et al.(2003) Peroxisomeproliferator-activated receptor delta controls muscle development and oxidative capability.FASEB J17(15):2299-301.
73. Ma J, Ren J, Guo Y, Duan Y, Ding N, et al.(2009) Genome-wide identification ofquantitative trait loci for carcass composition and meat quality in a large-scale White Duroc×Chinese Erhualian resource population. Anim Genet40(5):637-47.
74. Ma J, Yang J, Zhou L, Zhang Z, Ma H, et al.(2013) Genome-wide association study of meatquality traits in a white duroc×erhualian f2intercross and chinese sutai pigs. PLoS One8:e64047.
75. MacDougald OA, Lane MD. Transcriptional regulation of gene expression during adipocytedifferentiation. Annu Rev Biochem.1995,64:345-73.
76. Madsen P, Sorensen P, Su G, Damgaard LH, Thomsen H, Labouriau R. DMU-a package foranalyzing multivariate mixed models. In8thWorld Congress on Genetics Applied toLivestock Production. Brasil,2006.
77. Mai MD, Sahana G, Christiansen FB, Guldbrandtsen B: A genome-wide association study formilk production traits in Danish Jersey cattle using a50K single nucleotide polymorphismchip. J AnimSci2010,88:3522-3528.
78. Martin ER, Monks SA, Warren LL, Kaplan NL. A test for linkage and association in generalpedigres: the pedigree disequilibrium test. Am J Hum Genet.2000,67(1):146-54.
79. McCarthy MI, Hirschhorn JN. Genome-wide association studies: potential next steps on agenetic journey. Hum Mol Genet,2008,17:156-165.
80. Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature,2004,431(7006):343-349.
81. Melillo RM, Pierantoni G, Scala S, Battista S, Fedele M, et al.(2001) Critical role of theHMGI(Y) proteins in adipocytic cell growth and differentiation. Mol Cell Biol.21(7):2485-95.
82. Milan D, Bidanel JP, Iannuccelli N, Riguet J, Amigues Y, et al.(2002) Detection ofquantitative trait loci for carcass composition traits in pigs. Genet Sel Evol34(6):705-28.
83. Minozzi G, Buggiotti L, Stella A, Strozzi F, Liuni M, Williams JL. Genetic loci involved inantibody response to Mycobacterium avium ssp. paratuberculosisi in cattle. PLoS One.2010,5(6):e11117.
84. Morris RW, Kaplan NL. On the advantage of haplotype analysis in the presence of multipledisease susceptibility allels. Genet Epidemiol.2002,23(3):221-33.
85. Murdoch BM, Murdoch GK, Settles M, McKay S, Williams JL, Moore SS. Genome-widescan identifies loci associated with classical BSE occurrence. PLoS One2011,6(11):e26819.
86. Nielsen R. Molecular signatures of natural selection. Annual Review of Genetics.2005,39:197-218.
87. Niu T, Qin ZS, Xu X, Liu JS. Bayesian haplotype inference for multiple linkedsingle-nucleotide polymorphisms. Am J Hum Genet.2002,70(1):157-69.
88. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression [J]. J Nutr,2000,130:3122S-3126S.
89. Osiecka B, Zougman A, Wisniewski JR, et al. Immunohistochemical and proteomicevaluation of nuclear ubiquitous casein and cyclin-dependent kinases substrate in invasiveductal carcinoma of the breast. J Biomed Biotechol,2009:919645.
90. Philippe L, Giulia C,Fruchart JC, et al. Sorting out the Roles of PPARa in Energymetabolism and vascular homeostasis, J Clin Invest,2006,116(3):571-580.
91. Pierantoni GM, Battista S, Pentimalli F, Fedele M, Visone R et al. A truncated HMGA1geneinduces proliferation of the3T3-L1pre-adipocytic cells: a model of human lippomas.
92. Poulos S P, Dodson M V, Hausman G J. Cell line models for differentiation: preadipocytesand adipocytes. Experimental Biology and Medicine.2010,235(10):1185-1193.
93. Rangwala SM, Lazar MA. Transcriptional control of adipogenesis [J]. Annu Rev Nutr,2000,20:535-59.
94. Reeves R. Nuclear functions of the HMG proteins. Biochim Biophys Acta.2010,1799(1-2):3-14.
95. Ren J, Duan Y, Qiao R, Yao F, Zhang Z, et al.(2011) A missense mutation in PPARD causes amajor QTL effect on ear size in pigs. PLoS Genet7(5): e1002043.
96. Ren J, Mao H, Zhang Z, Xiao S, Ding N, Huang L. A6-bp deletion in the TYRP1genecauses the brown colouration phenotype in Chinese indigenous pigs. Heredity2011,106:862-868.
97. Reynolds A, Leake D, Boese Q, et al. Rational siRNA design for RNA interference. NatBiotechnol.2004,22(3):326-30.
98. Rosen E D, Sarraf P, Troy A E, et al. PPARg Is Required for the Differentiation of AdiposeTissue In Vivo and In Vitro. Mol Cell,1999,4:611-617.
99. Rubinson D A, Dillon C P, Kwiatkowski A V, et al. A lentivirus-based system to functionallysilence genes in primary mammalian cells, stem cells and transgenic mice by RNAinterference. Nat Genet,2003,33:401-406.
100. Samani NJ, Erdmann J, Hall AS, et al. Genome-wide association analysis of coronary arterydisease. New Engl J Med.2007,357(5):443-453.
101. Sanchez MP, Riquet J, Iannuccelli N, Gogue J, Billon Y, et al.(2006) Effects of quantitativetrait loci on chromosomes1,2,4, and7on growth, carcass, and meat quality traits inbackcross Meishan×Large White pigs. J Anim Sci84(3):526-37.
102. Scherr M, Morgan MA, Eder M. Gene silencing mediated by small interfering RNAs inmammalian cells. Curt Med Chem.2003,10:245-256.
103. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator activated receptor(PPAR) in mediating the effects of fibrates and fatty acids on gene expression,J Lip Res,1996,37:907-925.
104. Schoonjans, K., Staels, B., and Auwerx J. The peroxisomal proliferator activated receptors(PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim.Biophys. Acta1996,1302:93–109.
105. Schopen GC, Visker MH, Koks PD, Mullaart E, van Arendonk JA, Bovenhuis H.Whole-genome association study for milk protein composition in dairy cattle. J Dairy Sci2011,94:3148-3158.
106. Scuteri A, Sanna S, Chen W, et al. Genome-wide association scan shows genetic variants inthe FTO gene are association with obesity-related traits. PLoS Genetics.2007,3(7):1200-1210.
107. Sgarra R, Lee J, Tessari M A, et al. The AT-hook of the chromatin architectural transcriptionfactor high mobility group A1a is arginine-methylated by protein arginine methyltransferase6. J Biol Chem,2006,281(7):3764-3772.
108. Shah SN, Cope L, Poh W, Belton A, Roy S, et al.(2013) HMGA1: a master regulator oftumor progression in triple-negative breast cancer cells. PLoS One.8(5): e63419.
109. Sijen T, Vijn I, Rebocho A, et al. Transcriptional and posttranscriptional gene silencing aremechanistically related. Curr Biol.2001,11(6):434-40.
110. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Optimal designs for two-stage genome-wideassociation studies. Genet Epidemiol.2007,31(7):776-788.
111. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A,Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV,Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P. A genome-wideassociation study identifies novel risk loci for type2diabetes. Nature2007,445(7130):881-5.
112. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstructionfrom population data. Am J Hum Genet.2001,68(4):978-89.
113. Sui G H, Soohoo C, Shi Y, et al. A DNA vector-based RNAi technology to suppress geneexpression in mammalian cells. Pro Natl Acad Sci USA,2002;99(8):5515-5520.
114. Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, et al. A single IGF1allel is a majordeterminant of small size in dogs. Science.2007,316L:112-115.
115. Tanaka T, Yamamoto J, Iwasaki S, Asaba H, Hamura H, et al.(2003) Activation ofperoxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletalmuscle and attenuates metabolic syndrome. Proc Natl Acad Sci U S A100(26):15924-9.
116. Tang QQ, Otto TC, Lane MD. CCAAT/enhancer-binding protein beta is required for mitoticclonal expansion during adipogenesis. Proc Natl Acad Sci USA.2003,100(3):850-5.
117. Thomas AP, Teri A. How to interpret a Genome-wide Association Study. JAMA.2008;299(11):1335-1344.
118. Tijsterman M, Kitting RF, Plasterk RHA. The genetics of RNA silencing. Annu Rev Genet,2002,36:489-519.
119. Tsai Y S, Maeda N. PPARy: A critical determinant of body fat distribution in humans andmice. Trends Cardiovasc Med,2005,15:81-85.
120. Tuschl T. Expanding small RNA interference. Nature Biotechnology,2002,20:446-448.
121. Vidal-Puig A J, Considine R V, et al. Peroxisome proliferator activated receptor geneexpression in human tissue. Effects of obesity, weight loss and regulation by insulin andglucocorticoid. J Clin Invest,1997,99:2416-2422.
122. Vreeland WN, Meagher RJ, Barron AE. Multiplexed, high-throughput genotyping bysingle-base extension and end-labeled free-solution electrophoresis. Anal Chem.2002,74(17):4328-33.
123. Wang J, Jiang J, Fu W, Jiang L, Ding X,et al.. A genome-wide detection of copy numbervariations using SNP genotyping arrays in swine. BMC Genomics2012,13:273.
124. Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L. Anutrient-sensing pathway regulatesleptin gene expression in muscle and fat. Nature.1998,393:684-8.
125. Wang, N.D,Finegold M J, Bradley A, et al Impaired energy homeostasis in CEBP alphaknockout mice. Science,1995,269:1108—1112.
126. Wang WY, Barratt BJ, Clayton DG, Todd JA. Genome-wide association studies: theoreticaland practical concerns. Nat Rev Genet.2005,6(2):109-18.
127. Weiner BE, Huang H, Dattilo BM, Nilges MJ, Fanning E, et al.(2007) An iron-sulfur clusterin the C-terminal domain of the p58subunit of human DNA primase. J Biol Chem282(46):33444-51.
128. Xavier RJ and Rioux JD. Genome-wide association studies: a new window intoimmune-meidiated disease. Nature Revoews Immumology.2008,8:631-643.
129. Yang HY, Cheng CF, Djoko B, Lian WS, Tu CF, et al.(2007) Transgenic overexpression ofthe secreted, extracellular EGF-CUB domain-containing protein SCUBE3induces cardiachypertrophy in mice. Cardiovasc Res75(1):139-47.
130. Yang Q, Cui J, Chazaro I, et al. Power and type Ι error rate of false discovery rate approachesin genome-wide association studies. BMC Genet.2005,6(suppl1): S134.
131. Yeh WC, Cao Z, Classon M, et al. Cascade regulation of terminal adipocyte differentiation bythree members of the C/EBP family of leucine zipper proteins. Genes Dev.1995,9(2):168-81.
132. Youssef J, Badr M. Role of Peroxisome Proliferator-activated Receptors in InflammationControl. JBiomed biotechnol,2004,(3):156-166.
133. Zerbe LK, Kuchta RD (2002) The p58subunit of human DNA primase is important forprimer initiation, elongation, and counting. Biochemistry41(15):4891-900.
134. Zhong J, Chaerkady R, Kandasamy K, Gucek M, Cole RN, et al.(2011) The interactome of aPTB domain-containing adapter protein, Odin, revealed by SILAC. J Proteomics74(3):294-303.