期刊论文详细信息
BMC Genetics
Genome-wide linkage analysis of QTL for growth and body composition employing the PorcineSNP60 BeadChip
M Carmen Rodríguez2  Josep María Folch4  Luis Silió2  Jose Luis Noguera3  Anna Castelló1  Noelia Ibáñez-Escriche3  Yuliaxis Ramayo-Caldas1  Carmen Barragán2  Dafne Pérez-Montarelo2  Ana I Fernández2 
[1] Departament de Ciència Animal i dels Aliments, Facultat de Veterinària, UAB, 08193, Bellaterra, Spain. Present address: Consorci CSIC-IRTA-UAB (Centre de Recerca en Agrigenòmica), Edifici CRAG, Campus UAB, Bellaterra, Spain;Departamento de Mejora Genética Animal, INIA, Ctra. De la Coruña km. 7, Madrid, 28040, Spain;Genètica i Millora Animal, IRTA Lleida, 25198, Lleida, Spain;Centre for Research in Agricultural Genomics (CRAG), Consortium CSIC-IRTA-UAB-UB. Edifici CRAG, Campus Universitat Autonoma Barcelona, 08193, Bellaterra, Spain
关键词: Body conformation;    Fatness;    Growth;    PorcineSNP60 Beadchip;    QTL;   
Others  :  1122460
DOI  :  10.1186/1471-2156-13-41
 received in 2012-02-27, accepted in 2012-04-30,  发布年份 2012
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【 摘 要 】

Background

The traditional strategy to map QTL is to use linkage analysis employing a limited number of markers. These analyses report wide QTL confidence intervals, making very difficult to identify the gene and polymorphisms underlying the QTL effects. The arrival of genome-wide panels of SNPs makes available thousands of markers increasing the information content and therefore the likelihood of detecting and fine mapping QTL regions. The aims of the current study are to confirm previous QTL regions for growth and body composition traits in different generations of an Iberian x Landrace intercross (IBMAP) and especially identify new ones with narrow confidence intervals by employing the PorcineSNP60 BeadChip in linkage analyses.

Results

Three generations (F3, Backcross 1 and Backcross 2) of the IBMAP and their related animals were genotyped with PorcineSNP60 BeadChip. A total of 8,417 SNPs equidistantly distributed across autosomes were selected after filtering by quality, position and frequency to perform the QTL scan. The joint and separate analyses of the different IBMAP generations allowed confirming QTL regions previously identified in chromosomes 4 and 6 as well as new ones mainly for backfat thickness in chromosomes 4, 5, 11, 14 and 17 and shoulder weight in chromosomes 1, 2, 9 and 13; and many other to the chromosome-wide signification level. In addition, most of the detected QTLs displayed narrow confidence intervals, making easier the selection of positional candidate genes.

Conclusions

The use of higher density of markers has allowed to confirm results obtained in previous QTL scans carried out with microsatellites. Moreover several new QTL regions have been now identified in regions probably not covered by markers in previous scans, most of these QTLs displayed narrow confidence intervals. Finally, prominent putative biological and positional candidate genes underlying those QTL effects are listed based on recent porcine genome annotation.

【 授权许可】

   
2012 Fernandez et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Fujii J, Otsu K, Zorzato F, de Leon S, Khanna VK, Weiler JE, O’Brien PJ, MacLennan DH: Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 199, 253:448-451.
  • [2]Milan D, Jeon JT, Looft C, Amarger V, Robic A, Thelander M, Rogel-Gaillard C, Paul S, Iannuccelli N, Rask L, Ronne H, Lundström K, Reinsch N, Gellin J, Kalm E, Roy PL, Chardon P, Andersson L: A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. Science 2000, 19:1248-1251.
  • [3]Van Laere AS, Nguyen M, Braunschweig M, Nezer C, Collette C, Moreau L, Archibald AL, Haley CS, Buys N, Tally M, Andersson G, Georges M, Andersson L: A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. Nature 2003, 425:832-836.
  • [4]Ciobanu DC, Bastiaansen J, Lonergan SM, Thomsen H, Dekkers JCM, Plastow GS, Rothschild MF: New alleles in calpastatin gene are associated with meat quality traits in pigs J Anim Sci. 2004, 82:2829-2839.
  • [5]Andersson L, Georges M: Domestic-animal genomics: deciphering the genetics of complex traits: Nat Rev Genet. 2004, 5:202-212.
  • [6]John S, Shephard N, Liu G, Zeggini E, Cao M, Chen W, Vasavda N, Mills T, Barton A, Hinks A, Eyre S, Jones KW, Ollier W, Silman A, Gibson N, Worthington J, Kennedy GC: Whole-genome scan, in a complex disease, using 11,245 single-nucleotide polymorphisms: comparison with microsatellites. Am J Hum Genet 2004, 75:54-64.
  • [7]Pérez-Enciso M, Varona L: Quantitative trait loci mapping in F2 crosses between outbred lines. Genetics 2000, 155:391-405.
  • [8]Varona L, Óvilo C, Clop A, Noguera JL, Pérez-Enciso M, Coll A, Folch JM, Barragán C, Toro MA, Babot D, Sánchez A: QTL mapping for growth and carcass traits in an Iberian by Landrace pig intercross: additive, dominant and epistatic effects. Genet Res 2002, 80:145-154.
  • [9]Mercadé A, Estellé J, Noguera JL, Folch JM, Varona L, Silió L, Sánchez A, Pérez-Enciso M: On growth, fatness, and form: a further look at porcine chromosome 4 in an Iberian x Landrace cross. Mamm Genome 2005, 16:374-382.
  • [10]Óvilo C, Pérez-Enciso M, Barragan C, Clop A, Rodriguez C, Oliver MA, Toro MA, Noguera JL: A QTL for intramuscular fat and backfat thickness is located on porcine chromosome 6. Mamm Genome 2000, 11:344-346.
  • [11]Óvilo C, Oliver A, Noguera JL, Clop A, Barragán C, Varona L, Rodríguez C, Toro MA, Sánchez A, Pérez-Enciso M, Silió L: Test for positional candidate genes for body composition on pig chromosome 6. Genet Sel Evol 2002, 34:465-479. BioMed Central Full Text
  • [12]Óvilo C, Fernández A, Noguera JL, Barragán C, Letón R, Rodríguez C, Mercadé A, Alves E, Folch JM, Varona L, Toro MA: Fine mapping of porcine chromosome 6 QTL and LEPR effects on body composition in multiple generations of an Iberian by Landrace intercross. Genet Res 2005, 85:57-67.
  • [13]Óvilo C, Fernández A, Fernández AI, Folch JM, Varona L, Benítez R, Nuñez Y, Rodríguez C, Silió L: Hypothalamic expression of porcine leptin receptor (LEPR), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript (CART) genes is influenced by LEPR genotype. Mamm Genome 2010, 21:583-591.
  • [14]Estellé J, Fernández AI, Pérez-Enciso M, Fernández A, Rodríguez C, Sánchez A, Noguera JL, Folch JM: A non-synonymous mutation in a conserved site of the MTTP gene is strongly associated with protein activity and fatty acid profile in pigs. Anim Genet 2009, 40:813-820.
  • [15]Estellé J, Pérez-Enciso M, Mercadé A, Varona L, Alves E, Sánchez A, Folch JM: Characterization of the porcine FABP5 gene and its association with the FAT1 QTL in an Iberian by Landrace cross. Anim Genet 2006, 37:589-591.
  • [16]Mercadé A, Pérez-Enciso M, Varona L, Alves E, Noguera JL, Sánchez A, Folch JM: Adipocyte fatty-acid binding protein is closely associated to the porcine FAT1 locus on chromosome 4. J Anim Sci 2006, 84:2907-2913.
  • [17]Evans DM, Cardon LR: Guidelines for genotyping in genomewide linkage studies: single-nucleotide-polymorphism maps versus microsatellite maps. Am J Hum Genet 2004, 75:687-692.
  • [18]Gonzalez-Neira A, Rosa-Rosa JM, Osorio A, Gonzalez E, Southey M, Sinilnikova O, Lynch H, Oldenburg RA, van Asperen CJ, Hoogerbrugge N, Pita G, Devilee P, Goldgar D, Benitez J: Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies. BMC Genomics 2007, 8:299. BioMed Central Full Text
  • [19]Chioza BA, Aicardi J, Aschauer H, Brouwer O, Callenbach P, Covanis A, Dooley JM, Dulac O, Durner M, Eeg-Olofsson O, Feucht M, Friis ML, Guerrini R, Kjeldsen MJ, Nabbout R, Nashef L, Sander T, Sirén A, Wirrell E, McKeigue P, Robinson R, Gardiner RM, Everett KV: Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14. Epilepsy Res 2009, 87:247-255.
  • [20]Ramos AM, Crooijmans RP, Affara NA, Amaral AJ, Archibald AL, Beever JE, Bendixen C, Churcher C, Clark R, Dehais P, Hansen MS, Hedegaard J, Hu ZL, Kerstens HH, Law AS, Megens HJ, Milan D, Nonneman DJ, Rohrer GA, Rothschild MF, Smith TP, Schnabel RD, Van Tassell CP, Taylor JF, Wiedmann RT, Schook LB, Groenen MA: Design of a high density SNP genotyping assay in the pig using SNPs identified and characterized by next generation sequencing technology. PLoS One 2009, 4:e6524.
  • [21]Muñoz M, Alves E, Ramayo-Caldas Y, Casellas J, Rodríguez C, Folch JM, Silió L, Fernández AI: Recombination rates across porcine autosomes inferred from high-density linkage maps. Anim Genet 2011.
  • [22]Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007, 81:559-275.
  • [23]Storey JD, Taylor JE, Siegmund D: Strong control, conservative point estimation, and simultaneous conservative consistency of false discovery rates: A unified approach. J R Stat Soc Series B 2004, 66:187-205.
  • [24]Mangin B, Goffinet B, Rebaï A: Constructing confidence intervals for QTL location. Genetics 1994, 138:1301-1308.
  • [25]Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21:263-265.
  • [26]Pérez-Enciso M: Misztal I. Qxpak.5: old mixed model solutions for new genomics problems. BMC Bioinformatics 2011, 12:202.
  • [27]Andersson L, Haley CS, Ellegren H, Knott SA, Johansson M, Andersson K, Andersson-Eklund L, Edfors-Lilja I, Fredholm M, Hansson I, et al.: Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science 1994, 263:1771-1774.
  • [28]Marklund L, Nyström PE, Stern S, Andersson-Eklund L, Andersson L: Confirmed quantitative trait loci for fatness and growth on pig chromosome 4. Heredity 1999, 82:134-141.
  • [29]Fan B, Onteru SK, Du ZQ, Garrick DJ, Stalder KJ, Rothschild MF: Genome-wide association study identifies Loci for body composition and structural soundness traits in pigs. PLoS One 2011, 6:e14726.
  • [30]Rohrer GA, Keele JW: Identification of quantitative trait loci affecting carcass composition in swine: I. Fat deposition traits. J Anim Sci 1998, 76:2247-2254.
  • [31]Rohrer GA: Identification of quantitative trait loci affecting birth characters and accumulation of backfat and weight in a Meishan-White Composite resource population. J Anim Sci 2000, 78:2547-2553.
  • [32]Bidanel JP, Milan D, Iannuccelli N, Amigues Y, Boscher MY, Bourgeois F, Caritez JC, Gruand J, Le Roy P, Lagant H, Quintanilla R, Renard C, Gellin J, Ollivier L, Chevalet C: Detection of quantitative trait loci for growth and fatness in pigs. Genet Sel Evol 2001, 33:289-309. BioMed Central Full Text
  • [33]Geldermann H, Cepica S, Stratil A, Bartenschlager H, Preuss S: Genome-wide mapping of quantitative trait loci for fatness, fat cell characteristics and fat metabolism in three porcine F2 crosses. Genet Sel Evol 2010, 42:31. BioMed Central Full Text
  • [34]Quintanilla R, Milan D, Bidanel JP: A further look at quantitative trait loci affecting growth and fatness in a cross between Meishan and Large White pig populations. Genet Sel Evol 2002, 34:193-210. BioMed Central Full Text
  • [35]Knott SA, Marklund L, Haley CS, Andersson K, Davies W, Ellegren H, Fredholm M, Hansson I, Hoyheim B, Lundström K, Moller M, Andersson L: Multiple marker mapping of quantitative trait loci in a cross between outbred wild boar and large white pigs. Genetics 1998, 149:1069-1080.
  • [36]Sławińska A, Siwek M, Knol EF, Roelofs-Prins DT, van Wijk HJ, Dibbits B, Bednarczyk M: Validation of the QTL on SSC4 for meat and carcass quality traits in a commercial crossbred pig population. J Anim Breed Genet 2009, 126:43-51.
  • [37]Edwards DB, Ernst CW, Tempelman RJ, Rosa GJ, Raney NE, Hoge MD, Bates RO: Quantitative trait loci mapping in an F2 Duroc x Pietrain resource population: I. Growth traits. J Anim Sci 2008, 86:241-253.
  • [38]Milan D, Bidanel JP, Iannuccelli N, Riquet J, Amigues Y, Gruand J, Le Roy P, Renard C, Chevalet C: Detection of quantitative trait loci for carcass composition traits in pigs. Genet Sel Evol 2002, 34:705-728. BioMed Central Full Text
  • [39]Guo T, Ren J, Yang K, Ma J, Zhang Z, Huang L: Quantitative trait loci for fatty acid composition in longissimus dorsi and abdominal fat: results from a White Duroc x Erhualian intercross F2 population. Anim Genet 2009, 40:185-191.
  • [40]Liu G, Kim JJ, Jonas E, Wimmers K, Ponsuksili S, Murani E, Phatsara C, Tholen E, Juengst H, Tesfaye D, Chen JL, Schellander K: Combined line-cross and half-sib QTL analysis in Duroc-Pietrain population. Mamm Genome 2008, 19:429-438.
  • [41]de Koning DJ, Harlizius B, Rattink AP, Groenen MA, Brascamp EW, van Arendonk JA: Detection and characterization of quantitative trait loci for meat quality traits in pigs. J Anim Sci 2001, 79:2812-2819.
  • [42]Xue HL, Zhou ZX: Effects of the MyoG gene on the partial growth traits in pigs. Yi Chuan Xue Bao 2006, 33:992-997.
  • [43]Kim CW, Hong YH, Yun SI, Lee SR, Kim YH, Kim MS, Chung KH, Jung WY, Kwon EJ, Hwang SS, Park DH, Cho KK, Lee JG, Kim BW, Kim JW, Kang YS, Yeo JS, Chang KT: Use of microsatellite markers to detect quantitative trait loci in Yorkshire pigs. J Reprod Dev 2006, 52:229-237.
  • [44]Liu G, Jennen DG, Tholen E, Juengst H, Kleinwächter T, Hölker M, Tesfaye D, Un G, Schreinemachers HJ, Murani E, Ponsuksili S, Kim JJ, Schellander K, Wimmers K: A genome scan reveals QTL for growth, fatness, leanness and meat quality in a Duroc-Pietrain resource population. Anim Genet 2007, 38:241-252.
  • [45]Xu XL, Xu XW, Pan PW, Li K, Jiang ZH, Yu M, Rothschild MF, Liu B: Porcine skeletal muscle differentially expressed gene CMYA1: isolation, characterization, mapping, expression and association analysis with carcass traits. Anim Genet 2009, 40:255-261.
  • [46]Ramos AM, Bastiaansen JW, Plastow GS, Rothschild MF: Genes located on a SSC17 meat quality QTL region are associated with growth in outbred pig populations. Anim Genet 2009, 40:774-778.
  • [47]Pierzchala M, Cieslak D, Reiner G, Bartenschlager H, Moser G, Geldermann H: Linkage and QTL mapping for Sus scrofa chromosome 17. J Anim Breed Genet 2003, 120:132-137.
  • [48]Russo V, Fontanesi L, Scotti E, Beretti F, Davoli R: Nanni Costa L, Virgili R, Buttazzoni L: Single nucleotide polymorphisms in several porcine cathepsin genes are associated with growth, carcass, and production traits in Italian Large White pigs. J Anim Sci 2008, 86:3300-3314.
  • [49]Tsai FJ, Yang CF, Chen CC, Chuang LM, Lu CH, Chang CT, Wang TY, Chen RH, Shiu CF, Liu YM, Chang CC, Chen P, Chen CH, Fann CS, Chen YT, Wu JY: A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet 2010, 6:e1000847.
  • [50]Handschin C, Spiegelman BM: Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 2006, 27:728-735.
  • [51]Silva KM, Bastiaansen JW, Knol EF, Merks JW, Lopes PS, Guimarães SE, van Arendonk JA: Meta-analysis of results from quantitative trait loci mapping studies on pig chromosome 4. Anim Genet 2011, 42:280-292.
  • [52]Fontanesi L, Scotti E, Buttazzoni L: Dall'Olio S, Davoli R, Russo V: A single nucleotide polymorphism in the porcine cathepsin K (CTSK) gene is associated with back fat thickness and production traits in Italian Duroc pigs. Mol Biol Rep 2010, 37:491-495.
  • [53]Ojeda A, Estellé J, Folch JM, Pérez-Enciso M: Nucleotide variability and linkage disequilibrium patterns at the porcine FABP5 gene. Anim Genet 2008, 39:468-473.
  • [54]Han SH, Shin KY, Lee SS, Ko MS, Jeong DK, Oh HS, Yang BC, Cho IC: SINE indel polymorphism of AGL gene and association with growth and carcass traits in Landrace x Jeju Black pig F(2) population. Mol Biol Rep 2010, 37:467-471.
  • [55]Fontanesi L, Galimberti G, Calò DG, Fronza R, Martelli PL, Scotti E, Colombo M, Schiavo G, Casadio R, Buttazzoni L, Russo V: Identification and association analysis of several hundred single nucleotide polymorphisms within candidate genes for backfat thickness in Italian Large White pigs using a selective genotyping approach. J Anim Sci 2012,  : . [Epub ahead of print]
  • [56]Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423:762-769.
  • [57]Grundberg E, Brändström H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A: Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 2004, 150:323-328.
  • [58]Lopez-Buesa P, Óvilo C, Rodríguez MC, Varona L, Silió L, Burgos C, Galve A: The effects of leptin receptor (LEPR) and melanocortin-4 receptor (MC4R) polymorphisms in fat content, fat distribution, and fat composition in a Duroc x Landrace/Large White cross. Livestock Science 2011.
  • [59]Muñoz G, Óvilo C, Silió L, Tomás A, Noguera JL, Rodriguez MC: Single- and joint population analyses of two experimental pig crosses to confirm quantitative trait loci on Sus scrofa chromosome 6 and leptin receptor effects on fatness and growth traits. J Anim Sci 2009, 87:459-468.
  • [60]Muñoz G, Alcázar E, Fernández A, Barragán C, Carrasco A, de Pedro E, Silió L, Sánchez JL, Rodríguez MC: Effects of porcine MC4R and LEPR polymorphisms, gender and Duroc sire line on economic traits in Duroc x Iberian crossbred pigs. Meat Sci 2011, 88:169-173.
  • [61]Rodriguez MC, Fernandez A, Carrasco C, Garcia A, Gomez E, De Mercado E, Lopez MA, Óvilo C, Silio L: Effect of LEPR c.2002 C>T SNP on feed intake and growth in heavy Duroc X Iberian crossbred pigs. In Proceedings of the ninth world congress on genetics applied to livestock production 2010,  :1-6. Leipzig
  • [62]Krzęcio E, Koćwin-Podsiadła M, Kurył J, Zybert A, Sieczkowska H, Antosik K: The effect of interaction between genotype CAST/RsaI (calpastatin) and MYOG/MspI (myogenin) on carcass and meat quality in pigs free of RYR1(T) allele. Meat Sci 2008, 80:1106-1115.
  • [63]Wyszyńska-Koko J, Pierzchała M, Flisikowski K, Kamyczek M, Rózycki M, Kurył J: Polymorphisms in coding and regulatory regions of the porcine MYF6 and MYOG genes and expression of the MYF6 gene in m. longissimus dorsi versus productive traits in pigs. J Appl Genet 2006, 47:131-138.
  • [64]Ikeda T, Kanazawa T, Otsuka S, Ichii O, Hashimoto Y, Kon Y: Expression of caspase family and muscle- and apoptosis-specific genes during skeletal myogenesis in mouse embryo. J Vet Med Sci 2009, 71:1161-1168.
  • [65]Squires EJ: Lundström: Relationship between cytochrome P450IIE1 in liver and levels of skatole and its metabolites in intact male pigs. J Anim Sci 1997, 75:2506-2511.
  • [66]Babol J, Squires EJ, Lundström K: Hepatic metabolism of skatole in pigs by cytochrome P4502E1. J Anim Sci 1998, 76:822-828.
  • [67]Lin Z, Lou Y, Squires EJ: Functional polymorphism in porcine CYP2E1 gene: Its association with skatole levels. J Steroid Biochem Mol Biol 2006, 99:231-237.
  • [68]Zong H, Armoni M, Harel C, Karnieli E, Pessin JE: Cytochrome P450 CYP2E1 knockout mice are protected against high fat diet induced obesity and insulin resistance. Am J Physiol Endocrinol Metab 2011.
  • [69]Aubert J, Begriche K, Knockaert L, Robin MA, Fromenty B: Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol 2011, 35:630-637.
  • [70]Latreille M, Laberge MK, Bourret G, Yamani L, Larose L: Deletion of Nck1 attenuates hepatic ER stress signaling and improves glucose tolerance and insulin signaling in liver of obese mice. Am J Physiol Endocrinol Metab 2011, 300:E423-434.
  • [71]Akerfeldt MC, Laybutt DR: Inhibition of Id1 augments insulin secretion and protects against high-fat diet-induced glucose intolerance. Diabetes 2011, 60:2506-2514.
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