Abstract
The aim of this study was to analyze the association between the copy number variation regions (CNVRs) and fatty acid profile phenotypes for saturated (SFA), monosaturated (MUFA), polyunsaturated (PUFA), ω6 and ω3 fatty acids, PUFA/SFA and ω6/ω3 ratios, as well as for their sums, in Nellore cattle (Bos primigenius indicus). A total of 963 males were finished in feedlot and slaughtered with approximately 2 years of age. Animals were genotyped with the BovineHD BeadChip (Illumina Inc., San Diego, CA, USA). The copy number variation (CNV) detection was performed using the PennCNV algorithm. Log R ratio (LRR) and allele B frequency (BAF) were used to estimate the CNVs. The association analyses were done using the CNVRuler software and applying a logistic regression model. The phenotype was adjusted using a linear model considering the fixed effects of contemporary group and the animal age at slaughter. The fatty acid profile was analyzed on samples of longissimus thoracis muscle using gas chromatography with a 100-m capillary column. For the association analysis, the adjusted phenotypic values were considered for the traits, while the data was adjusted for the effects of the farm and year of birth, management groups at birth, weaning, and superannuation. A total of 186 CNVRs were significant for SFA (43), MUFA (42), PUFA (66), and omega fatty acid (35) groups, totaling 278 known genes. On the basis of the results, several genes were associated with several fatty acids of different saturations. Olfactory receptor genes were associated with C12:0, C14:0, and C18:0 fatty acids. The SAMD8 and BSCL2 genes, both related to lipid metabolic process, were associated with C12:0. The RAPGEF6 gene was found to be associated with C18:2 cis-9 cis-12 n-6, and its function is related to regulation of GTPase activity. Among the results, we highlighted the olfactory receptor activity (GO:0004984), G-protein-coupled receptor activity (GO:0004930), potassium:proton antiporter activity (GO:0015386), sodium:proton antiporter activity (GO:0015385), and odorant-binding (GO:0005549) molecular functions. A large number of genes associated with fatty acid profile within the CNVRs were identified in this study. These findings must contribute to better elucidate the genetic mechanism underlying the fatty acid profile of intramuscular fat in Nellore cattle.
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Abbreviations
- MUFA :
-
Sum of monounsaturated fatty acids
- FA :
-
Fatty acid
- CNV :
-
Copy number variation
- CNVR :
-
Copy number variation regions
- GWAS :
-
Genome-wide association study
- QTL :
-
Quantitative trait loci
- PUFA :
-
Sum of polyunsaturated fatty acids
- CLA :
-
Conjugated linoleic acid
- GO :
-
Gene ontology
- MAF :
-
Minor allele frequency
- SFA :
-
Sum of saturated fatty acids
- ω3 :
-
Sum of omega 3 acids
- ω6 :
-
Sum of omega 6 acids
- BAF :
-
Allele B frequency
- IMF :
-
Intramuscular fat
- LDL :
-
Low-density lipoprotein
- BTA :
-
Bos Taurus chromosome
- LRR :
-
Log R ratio
- SNP :
-
Single nucleotide polymorphism
References
Abo-ismail MK, Vander VG, Squires JJ et al (2014) Single nucleotide polymorphisms for feed efficiency and performance in crossbred beef cattle. BMC Genomics 15:14
Aboujaoude C, Pereira ASC, Feitosa FLB et al (2016) Genetic parameters for fatty acids in intramuscular fat from feedlot-finished Nelore carcasses. Anim Prod Sci. https://doi.org/10.1071/AN16107
Ashburner M, Ball CA, Blake JA et al (2011) Gene ontology: tool for the unification of biology. Nat Genet 25:25–29. https://doi.org/10.1038/75556.Gene
Ashraf S, Gee HY, Woerner S et al (2013) ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ 10 biosynthesis disruption. J Clin Invest 123:5179–5189. https://doi.org/10.1172/JCI69000.The
Berghs S, Aggujaro D, Dirkx R et al (2000) βiv spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system. J Cell Biol 151:985–1001
Bertics SJ, Grummer RR, Cadorniga-Valino C, Stoddard EE (1992) Prepartum dry matter intake on liver triglyceride concentration and early lactation. J Dairy Sci 75:1914–1922. https://doi.org/10.3168/jds.S0022-0302(92)77951-X
Berton MP, Fonseca LFS, Gimenez DFJ et al (2016) Gene expression profile of intramuscular muscle in Nellore cattle with extreme values of fatty acid. BMC Genomics 17:972. https://doi.org/10.1186/s12864-016-3232-y
Blesh A, Boberhoff A-K, Apfel R, et al (1994) Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA1. Cancer Res 54:5695–5701
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917
Buchanan JW, Garmyn AJ, Hilton GG et al (2014) Comparison of gene expression and fatty acid profiles in concentrate and forage finished beef. J Anim Sci 91:1–9. https://doi.org/10.2527/jas2012-5154
Cesar AS, Regitano LC, Tullio RR et al (2014) Genome-wide association study for intramuscular fat deposition and composition in Nellore cattle. BMC Genet 15:39. https://doi.org/10.1186/1471-2156-15-39
Chen SL, Wang SM, Hosking B, Muscat GEO (2001) Subcellular localization of the steroid receptor coactivators (SRCs) and MEF2 in muscle and rhabdomyosarcoma cells. Mol Endocrinol 15:783–796
Chi A, Valencia JC, Hu Z et al (2006) Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes research articles. J Proteomic Res 5:3135–3144
Do Prado IN, Barros Moreira F, Matsushita M, De Souza NE (2003) Longissimus dorsi fatty acids composition of Bos indicus and Bos indicus x Bos taurus crossbred steers finished in pasture. Braz Arch Biol Technol 46:601–608. https://doi.org/10.1590/S1516-89132003000400015
Do DN, Strathe AB, Ostersen T et al (2014) Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake. Front Genet 5:1–10. https://doi.org/10.3389/fgene.2014.00307
Eckel-Passow JE, Atkinson EJ, Maharjan S et al (2011) Software comparison for evaluating genomic copy number variation for Affymetrix 6.0 SNP array platform. BMC Bioinformatics 12:220. https://doi.org/10.1186/1471-2105-12-220
Epping MT, Wang L, Carlée MJEL et al (2005) The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 122:835–847. https://doi.org/10.1016/j.cell.2005.07.003
Faucitano L, Chouinard PY, Fortin J et al (2008) Comparison of alternative beef production systems based on forage finishing or grain-forage diets with or without growth promotants: 2. Meat quality, fatty acid composition, and overall palatability. J Anim Sci 86:1678–1689. https://doi.org/10.2527/jas.2007-0756
Fellermann K, Stange DE, Schaeffeler E et al (2006) A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 79:439–448. https://doi.org/10.1086/505915
Folch J, Lees M, Stanley SGH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509
Hanchate NK, Giacobini P, Lhuillier P et al (2012) SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS One 8:1–9. https://doi.org/10.1371/journal.pgen.1002896
He L, Vasiliou K, Nebert DW (2009) Analysis and update of the human solute carrier (SLC) gene superfamily. Hum Genomics 3:195–206
Hu Z, Park CA, Wu X, Reecy JM (2013) Animal QTLdb: an improved database tool for livestock animal QTL/association data dissemination in the post-genome era. Nucleic Acids Res 41:871–879. https://doi.org/10.1093/nar/gks1150
Huang DW, Lempicki RA, Sherman BT (2009a) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. https://doi.org/10.1038/nprot.2008.211
Huang DW, Sherman BT, Lempicki RA (2009b) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1–13. https://doi.org/10.1093/nar/gkn923
Ishii A, Yamaji K, Uemoto Y et al (2013) Genome-wide association study for fatty acid composition in Japanese black cattle. Anim Sci J 84:675–682. https://doi.org/10.1111/asj.12063
Kantartzis K, Machicao F, Machann J et al (2009) The DGAT2 gene is a candidate for the dissociation between fatty liver and insulin resistance in humans. Clin Sci 116:531–537. https://doi.org/10.1042/CS20080306
Kim JH, Hu HJ, Yim SH et al (2012) CNVRuler: a copy number variation-based case-control association analysis tool. Bioinformatics 28:1790–1792. https://doi.org/10.1093/bioinformatics/bts239
Koike T, Izumikawa T, Sato B, Kitagawa H (2014) Identification of phosphatase that dephosphorylates xylose in the glycosaminoglycan-protein linkage region of proteoglycans. J Biol Chem 289:6695–6708. https://doi.org/10.1074/jbc.M113.520536
Koyama N, Kurihara K (1972) Effect of odorants on lipid monolayers from bovine olfactory epithelium. Nature 236:402–404
Kramer JKG, Fellner V, Dugan MER et al (1997) Evaluating acid and base catalysts in the methylation of milk and rumen fatty acids with special emphasis on conjugated dienes and total trans fatty acids. Lipids 32:1219–1228
Lee K, Nguyen DT, Choi M et al (2013) Analysis of cattle olfactory subgenome: the first detail study on the characteristics of the complete olfactory receptor repertoire of a ruminant. BMC Genomics 14:596
Lemos MVA, Chiaia HLJ, Berton MP et al (2016) Genome-wide association between single nucleotide polymorphisms with beef fatty acid profile in Nellore cattle using the single step procedure. BMC Genomics 17:213. https://doi.org/10.1186/s12864-016-2511-y
Liu Y, Li N, You L, et al (2008) HSP70 is associated with endothelial activation in placental vascular diseases. Mol Med 14(9–10):561–566
Liu GE, Hou Y, Zhu B, et al (2010) Analysis of copy number variations among diverse cattle breeds. Genome Res 20(5):693–703
Ma M (2007) Encoding olfactory signals via multiple chemosensory systems. Crit Rev Biochem Mol Biol 42:463–480. https://doi.org/10.1080/10409230701693359
Malnic B, Godfrey PA, Buck LB (2004) The human olfactory receptor gene family. Proc Natl Acad Sci U S A 101:2584–2589
Markley JC, Sadelain M (2010) IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice. Blood 115:3508–3520. https://doi.org/10.1182/blood-2009-09-241398.The
Mensink RP, Katan MB (1992) Effect of dietary fatty acids on serum lipids and lipoproteins—a meta-analysis of 27 trials. Arter Thromb 12:911–919. https://doi.org/10.1161/01.ATV.12.8.911
Miki H, Suetsugu S, Takenawa T (1998) WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J 17:6932–6941
Mills SJ, Vandeput F, Trusselle MN et al (2008) Benzene polyphosphates as tools for cell signalling: inhibition of inositol 1,4,5-trisphosphate 5-phosphatase and interaction with the PH domain of protein kinase Bα. Chembiochem 9:1757–1766. https://doi.org/10.1002/cbic.200800104.Benzene
Moreno-De-Luca D, Mulle JG, Kaminsky EB et al (2010) Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet 87:618–630. https://doi.org/10.1016/j.ajhg.2010.10.004
Nicklas TA, Dwyer J, Feldman H, et al (2002) Serum cholesterol levels in children are associated with dietary fat and fatty acid intake. J Am Diet Assoc 102(4):511–517
Niimura Y, Nei M (2007) Extensive gains and losses of olfactory receptor genes in mammalian evolution. PLoS One:1–8. https://doi.org/10.1371/journal.pone.0000708
Olivieri BF, Mercadante MEZ, Noely J, et al (2016) Genomic regions associated with feed efficiency indicator traits in an experimental Nellore cattle population. PLoS One 1–19. https://doi.org/10.1371/journal.pone.0164390
Paudel Y, Madsen O, Megens H-J et al (2015) Copy number variation in the speciation of pigs: a possible prominent role for olfactory receptors. BMC Genomics 16:330. https://doi.org/10.1186/s12864-015-1449-9
Payen E, Verkerk T, Michalovich D et al (1998) The centromeric/nucleolar chromatin protein ZFP-37 may function to specify neuronal nuclear domains*. J Biol Chem 273:9099–9109
Payne VA, Grimsey N, Tuthill A et al (2008) The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation. Diabetes 57:2055–2060. https://doi.org/10.2337/db08-0184
Pitchford WS, Deland MPB, Siebert BD et al (2002) Genetic variation in fatty acid composition of subcutaneous fat in cattle. J Anim Sci 80:2825–2832
Riley B, Thiselton D, Maher BS et al (2010) Replication of association between schizophrenia and ZNF804A in the Irish Case Control Study of Schizophrenia (ICCSS) sample. Mol Psychiatry 15:29–37. https://doi.org/10.1038/mp.2009.109.Replication
Sanders J, Maassen JA, Moller W (1992) Elongation factor-1 messenger-RNA levels in cultured cells are high compared to tissue and are not drastically affected further by oncogenic transformation. Nucleic Acids Res 20:5907–5910
Sebat J, Lakshmi B, Malhotra D et al (2007) Strong association of de novo copy number mutations with autism. Science 316:445–449. https://doi.org/10.1126/science.1138659
Sevane N, Armstrong E, Wiener P et al (2014) Polymorphisms in twelve candidate genes are associated with growth, muscle lipid profile and meat quality traits in eleven European cattle breeds. Mol Biol Rep 41:4721–4731. https://doi.org/10.1007/s11033-014-3343-y
Shi Y, Zhang L, Yang T (2014) Nuclear export of L-periaxin, mediated by its nuclear export signal in the PDZ domain. PLoS One 9:e91953. https://doi.org/10.1371/journal.pone.0091953
Slepkov ER, Rainey JK, Li X et al (2005) Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem 280:17863–17872. https://doi.org/10.1074/jbc
Smedley D, Haider S, Durinck S et al (2015) The BioMart community portal: an innovative alternative to large, centralized data repositories. Nucleic Acids Res 43:W589–W598. https://doi.org/10.1093/nar/gkv350
Sofer A, Lei K, Johannessen CM, Ellisen LW (2005) Regulation of mTOR and cell growth in response to energy stress by REDD1. Mol Cell Biol 25:5834–5845. https://doi.org/10.1128/MCB.25.14.5834
Strotmann J, Breer H (2011) Internalization of odorant-binding proteins into the mouse olfactory epithelium. Histochem Cell Biol 136:357–369. https://doi.org/10.1007/s00418-011-0850-y
Tapiero H, Nguyen Ba G, Couvreur P, Tew KD (2002) Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. Biomed Pharmacother 56:215–222. https://doi.org/10.1016/S0753-3322(02)00193-2
Walsh T, McClellan JM, McCarthy SE et al (2008) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539–543. https://doi.org/10.1126/science.1155174
Wang K, Li M, Hadley D et al (2007) PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res 17:1665–1674. https://doi.org/10.1101/gr.6861907
Winchester L, Yau C, Ragoussis J (2009) Comparing CNV detection methods for SNP arrays. Brief Funct Genomics Proteomics 8:353–366. https://doi.org/10.1093/bfgp/elp017
Wood JD, Enser M, Fisher AV et al (2008) Fat deposition, fatty acid composition and meat quality: a review. Meat Sci 78:343–358. https://doi.org/10.1016/j.meatsci.2007.07.019
Xie YR, Busboom JR, Gaskins CT et al (1996) Effects of breed and sire on carcass characteristics and fatty acid profiles of crossbred Wagyu and Angus steers. Meat Sci 43:167–177
Xu L, Cole JB, Bickhart DM et al (2014a) Genome wide CNV analysis reveals additional variants associated with milk production traits in Holsteins. BMC Genomics 15:683
Xu L, Hou Y, Bickhart DM et al (2014b) A genome-wide survey reveals a deletion polymorphism associated with resistance to gastrointestinal nematodes in Angus cattle. Funct Integr Genomic 14:333–339. https://doi.org/10.1007/s10142-014-0371-6
Zhang F, Gu W, Hurles ME, Lupski JR (2009) Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet 10:451–481. https://doi.org/10.1146/annurev.genom.9.081307.164217.Copy
Zhang Q, Ma Y, Wang X et al (2015) Identification of copy number variations in Qinchuan cattle using BovineHD genotyping Beadchip array. Mol Gen Genomics 290:319–327. https://doi.org/10.1007/s00438-014-0923-4
Zhou Y, Utsunomiya YT, Xu L et al (2016) Genome-wide CNV analysis reveals variants associated with growth traits in Bos indicus. BMC Genomics 17:419. https://doi.org/10.1186/s12864-016-2461-4
Zhu J, Larman HB, Gao G et al (2013) Protein interaction discovery using parallel analysis of translated ORFs (PLATO). Nat Biotechnol 31:331–334. https://doi.org/10.1038/nbt.2539.Protein
Funding
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) with grant numbers (#2013/11853-4, #2011/2141-0, and #2009/16118-5). MVA Lemos, FLB Feitosa, and E Peripolli received support from FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo. HLJ Chiaia, MP Berton, S Kluska, and BF Olivieri received scholarships from the Coordination Office for Advancement of University-level Personnel (CAPES; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) in conjunction with the Postgraduate Program on Genetics and Animal Breeding, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista (FCAV, UNESP). F Baldi received support from FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo grant #2011/21241-0 and Lucia G. Albuquerque from FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo grant #2009/16118-5.
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MVAL, FLBF, MPB, ASCP, and FB conceived and designed the experiment; MVAL, MPB, HLJC, FLBF, EP, SK, BFO, NBS, AMF, LFM, RLT, LGA, and HN performed the experiments; MVAL, HN, ASCP, NBS, and FB did analysis and interpretation of results; MVAL, ACSP, and FB drafted the manuscript. All authors read and approved the final manuscript.
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This study was approved by the ethics committee of the Faculdade de Ciências Agrárias e Veterinárias (FCAV), Universidade Estadual Paulista (UNESP), Jaboticabal-SP, Brazil.
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Communicated by: Maciej Szydlowski
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de Lemos, M.V.A., Peripolli, E., Berton, M.P. et al. Association study between copy number variation and beef fatty acid profile of Nellore cattle. J Appl Genetics 59, 203–223 (2018). https://doi.org/10.1007/s13353-018-0436-7
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DOI: https://doi.org/10.1007/s13353-018-0436-7