Expression-based GWAS identifies variants, gene interactions and key regulators affecting intramuscular fatty acid content and composition in porcine meat.
The aim of this work is to better understand the genetic mechanisms determining two complex traits affecting porcine meat quality: intramuscular fat (IMF) content and its fatty acid (FA) composition. With this purpose, expression Genome-Wide Association Study (eGWAS) of 45 lipid-related genes associated with meat quality traits in swine muscle (Longissimus dorsi) of 114 Iberian × Landrace backcross animals was performed. The eGWAS identified 241 SNPs associated with 11 genes: ACSM5, CROT, FABP3, FOS, HIF1AN, IGF2, MGLL, NCOA1, PIK3R1, PLA2G12A and PPARA. Three expression Quantitative Trait Loci (eQTLs) for IGF2, ACSM5 and MGLL were identified, showing cis-acting effects, whereas 16 eQTLs had trans regulatory effects. A polymorphism in the ACSM5 promoter region associated with its expression was identified. In addition, strong candidate genes regulating ACSM5, FOS, PPARA, PIK3R1, PLA2G12A and HIF1AN gene expression were also seen. Notably, the analysis highlighted the NR3C1 transcription factor as a strong candidate gene involved in the regulation of the 45 genes analysed. Finally, the IGF2, MGLL, MC2R, ARHGAP6, and NR3C1 genes were identified as potential regulators co-localizing within QTLs for fatness and growth traits in the IBMAP population. The results obtained increase our knowledge in the functional regulatory mechanisms involved in these complex traits.
Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.|Plant and Animal Genomics, Centre de Recerca en Agrigenòmica (CRAG), 08193 Bellaterra, Spain.
Anna
A
Puig-Oliveras
Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.|Plant and Animal Genomics, Centre de Recerca en Agrigenòmica (CRAG), 08193 Bellaterra, Spain.
Manuel
M
Revilla
Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.|Plant and Animal Genomics, Centre de Recerca en Agrigenòmica (CRAG), 08193 Bellaterra, Spain.
Anna
A
Castelló
Departamento de Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain.
Ana I
AI
Fernández
Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.|Plant and Animal Genomics, Centre de Recerca en Agrigenòmica (CRAG), 08193 Bellaterra, Spain.
Josep M
JM
Folch
Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.|Plant and Animal Genomics, Centre de Recerca en Agrigenòmica (CRAG), 08193 Bellaterra, Spain.|Departament de Genètica i Millora Animal, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Torre Marimon, 08140 Caldes de Montbui, Spain.
Maria
M
Ballester
BMC Genomics. 2013 Dec 02;14:845
24295214
Mol Med. 1997 Oct;3(10):663-73
9392003
Nat Genet. 2005 Jul;37(7):710-7
15965475
PLoS One. 2013 Nov 18;8(11):e80385
24260380
Development. 2013 Jan 1;140(1):126-35
23175628
BMC Genomics. 2014 Mar 26;15:232
24666776
Mamm Genome. 2003 Sep;14(9):650-6
14629115
Nucleic Acids Res. 2015 Jan;43(Database issue):D726-36
25348401
Front Genet. 2012 Jan 05;2:101
22303395
PLoS One. 2014 Jun 13;9(6):e99720
24926690
Nucleic Acids Res. 2015 Jul 1;43(W1):W589-98
25897122
Clin Cancer Res. 2002 Dec;8(12 ):3824-31
12473596
Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19529-36
23151514
Mamm Genome. 2000 Apr;11(4):344-6
10754115
Traffic. 2012 May;13(5):650-64
22321063
Meat Sci. 2003 Aug;64(4):499-506
22063133
Physiol Genomics. 2009 Dec 30;40(1):34-47
19808840
J Anim Sci. 2008 Dec;86(12):3290-9
18641172
Ann Med. 2011 May;43(3):198-211
21345154
PLoS One. 2011;6(6):e19521
21738568
Bioinformatics. 2002 Nov;18(11):1542-3
12424129
BMC Bioinformatics. 2011 May 25;12:202
21612630
Genet Sel Evol. 2002 Jul-Aug;34(4):465-79
12270105
Adv Genet. 2008;60:3-34
18358314
Atherosclerosis. 2014 Jun;234(2):320-8
24727233
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
12883005
J Anim Sci. 2010 Jul;88(7):2235-45
20382874
Diabetes. 2004 Dec;53(12):3097-106
15561939
J Mol Signal. 2010 Feb 18;5(1):1
20167101
Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5753-8
21436039
Drug Discov Today Dis Mech. 2013 Jun 1;10(1-2):e35-e40
23997790
Mamm Genome. 2005 May;16(5):374-82
16104385
Circ Cardiovasc Genet. 2014 Aug;7(4):491-504
24871327
Meat Sci. 2008 Apr;78(4):343-58
22062452
Nature. 2003 Oct 23;425(6960):832-6
14574411
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14608-13
21873205
Trends Genet. 2008 Aug;24(8):408-15
18597885
BMC Genet. 2012 May 20;13:41
22607048
Acta Physiol (Oxf). 2009 Nov;197(3):207-15
19508405
PLoS Comput Biol. 2014 Jul 24;10(7):e1003731
25058159
Nat Med. 2010 Mar;16(3):313-8
20154695
Hepatology. 2012 Jul;56(1):95-107
22278400
PLoS One. 2011;6(8):e23506
21858147
Nucleic Acids Res. 2013 Jan;41(Database issue):D871-9
23180796
PLoS One. 2009 Aug 05;4(8):e6524
19654876
J Anim Sci. 2000 Oct;78(10):2525-31
11048916
BMC Genomics. 2010 Nov 24;11:659
21106073
Horm Metab Res. 2012 Sep;44(9):670-5
22723268
J Anim Sci. 2006 Jun;84(6):1577-83
16699115
Cancer Res. 2004 Jan 15;64(2):456-62
14744756
Meat Sci. 2015 Dec;110:46-51
26172243
Nucleic Acids Res. 2010 Jan;38(Database issue):D690-8
19906730
J Clin Endocrinol Metab. 2001 May;86(5):2270-4
11344238
Bioinformatics. 2010 Aug 15;26(16):2069-70
20562413
Bioinformatics. 2005 Apr 1;21(7):1280-1
15546938
J Anim Sci. 2005 Dec;83(12):2723-8
16282609
Mol Cell Endocrinol. 2013 Feb 25;366(2):135-51
22750049
Nucleic Acids Res. 2012 Jan;40(Database issue):D144-9
22080564
Carbohydr Res. 2008 Aug 11;343(12):2024-31
18353293
J Anim Sci. 2012 Sep;90(9):2883-93
22785162
Anim Genet. 2009 Dec;40(6):813-20
19496770
Mol Biol Cell. 2009 Oct;20(20):4400-11
19710422
PLoS One. 2014 Dec 11;9(12):e114862
25503799