Integration of liver gene coexpression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs
Ballester, Maria | Ramayo Caldas, Yuliaxis | Revilla, Manuel | Corominas, Jordi | Castello, Anna | Estellé, Jordi | Fernandez, Ana I. | Folch, Josep M. | Departament de Ciència Animal i dels Aliments, Facultat de Veterinària ; Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona (UAB) | Plant and Animal Genomics, Centre de Recerca en Agrigenòmica (Consorci CSIC-IRTA-UAB-UB) ; Centre de Recerca en Agrigenòmica | Consejo Superior de Investigaciones Cientificas [España] = Spanish National Research Council [Spain] (CSIC) | Institut de Recerca i Tecnologia Agroalimentàries = Institute of Agrifood Research and Technology (IRTA) | Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona (UAB) | Genètica i Millora Animal ; Centre IRTA-Lleida | Génétique Animale et Biologie Intégrative (GABI) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech | Departamento de Mejora Genética Animal ; Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA) | European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014)
In the present study, liver co-expression networks and expression Genome Wide Association Study (eGWAS) were performed to identify DNA variants and molecular pathways implicated in the functional regulatory mechanisms of meat quality traits in pigs. With this purpose, the liver mRNA expression of 44 candidates genes related with lipid metabolism was analysed in 111 Iberian x Landrace backcross animals. The eGWAS identified 92 eSNPs located in seven chromosomal regions and associated with eight genes: CROT, CYP2U1, DGAT1, EGF, FABP1, FABP5, PLA2G12A, and PPARA. Remarkably, cis-eSNPs associated with FABP1 gene expression which may be determining the C18: 2(n-6)/C18: 3(n-3) ratio in backfat through the multiple interaction of DNA variants and genes were identified. Furthermore, a hotspot on SSC8 associated with the gene expression of eight genes was identified and the TBCK gene was pointed out as candidate gene regulating it. Our results also suggested that the PI3K-Akt-mTOR pathway plays an important role in the control of the analysed genes highlighting nuclear receptors as the NR3C1 or PPARA. Finally, sex-dimorphism associated with hepatic lipid metabolism was identified with over-representation of female-biased genes. These results increase our knowledge of the genetic architecture underlying fat composition traits.
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