Integration of liver gene co-expression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs.
Integration of liver gene co-expression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs.
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DOI：
10.1038/srep46539
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发表时间：
2017-04-19
影响因子：
4.6
通讯作者：
Folch JM
中科院分区：
文献类型：
--
作者：
Ballester M;Ramayo-Caldas Y;Revilla M;Corominas J;Castelló A;Estellé J;Fernández AI;Folch JM
本研究利用肝脏共表达网络和表达基因组广谱关联研究(EGWAS)来鉴定与猪肉质性状功能调控机制相关的DNA变异和分子途径。为此，我们对111头伊比利亚×长白回交动物的44个与脂代谢相关的候选基因的肝脏mRNA表达进行了分析。该研究发现92个eSNP位于7个染色体区域，与8个基因相关：CROT、CYP2U1、DGAT1、EGF、FABP1、FABP5、PLA2G12A和PPARA。值得注意的是，发现了与FABP1基因表达相关的cis-eSNPs，该基因可能通过DNA变异体和基因的多重相互作用来决定背脂中C18：2(n-6)/C18：3(n-3)的比例。此外，还发现了SSC8上与8个基因表达相关的热点，并指出TBCK基因是调控该基因表达的候选基因。我们的结果还表明，PI3K-Akt-mTOR通路在控制NR3C1或PPARA等突出核受体的分析基因中发挥着重要作用。最后，与肝脏脂肪代谢相关的性别二型性被确认为女性偏向基因的过度表达。这些结果增加了我们对脂肪组成特征背后的遗传结构的了解。
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.