基于DNA甲基化分析的鸡脂肪肝跨代遗传分子机制研究

Fatty liver is widespread in laying hens which causes production performance decline and serious economic losses. The occurrence process of fatty liver is very complex, most of the studies focus on the cause and prevention at present, but the exact molecular mechanisms of fatty liver are still not clear. The previous studies of our team showed that the fatty liver was regulated by DNA methylation and could trans-generational inheritance. Based on this, we formulated fatty liver models of F0-F2 full sib. The key genes and methylation markers of fat liver were investigated subsequently according to the results of transcriptome sequencing, genome-wide DNA methylation sequencing and population identification in F0 full sib. And then the epigenetic regularities of key gene in F1 and F2 generation were analysised to reveal the correlations between fatty liver trans-generational inheritance and DNA methylation. Futher more fatty liver trans-generational inheritance are explain and analysis from epigenetic regulation. The result will provide basis for reveal the pathogenesis of fatty liver and disease resistant breeding in chicken.

脂肪肝在蛋鸡中普遍发生，导致产蛋性能下降，造成严重的经济损失。目前有关鸡脂肪肝的研究主要集中在病因和防治措施等方面，对其机制的探究较少且尚不明晰。项目申请人所在课题组前期研究发现鸡脂肪肝受DNA甲基化调控，能够跨代遗传。据此，本研究利用自主构建的F0-F2代全同胞脂肪肝模型，通过对F0代全同胞脂肪肝模型转录组测序和全基因组DNA甲基化测序，结合群体验证挖掘调控脂肪肝的关键基因和甲基化分子标记；分析关键基因DNA甲基化在F1和F2代中的遗传规律，揭示DNA甲基化与脂肪肝跨代遗传的相关性，进而从表观遗传学角度解析鸡脂肪肝跨代遗传的分子机制，为揭示鸡脂肪肝发病机制和抗病育种提供依据。

脂肪肝又称为脂肪肝综合征或脂肪肝出血综合征，由营养、激素，环境和遗传因素引起一种代谢性疾病。尽管在产蛋鸡中普遍发生，但由于其不像传染性疾病那么明显，因此往往被忽视。与传染性疾病相比，脂肪肝的死亡率较低，但它能够引起产蛋率、受精率和孵化率下降，对家禽产业造成严重的经济损失。正常生理状态下肝脂代谢处于动态平衡，当肝脏脂肪合成、脂肪酸β-氧化或脂蛋白转运发生异常，致使脂肪在肝中过度蓄积，从而诱发脂肪肝。目前有关鸡脂肪肝的研究主要集中在病因和防治措施等方面，对其机制的探究较少且尚不明晰。本研究通过高脂日粮和甲基缺失日粮诱导三个品种，获得脂肪肝易感品种，同时对易感品种脂肪肝表型遗传模式进行分析，结果表明脂肪肝能够通过父代进行遗传，在脂肪肝表型传代过程中包括ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 和 ME1等发挥重要作用。同时ACACA和SCD通过甲基化水平的改变调控其表达，进而影响高脂日粮诱导的脂肪肝表型遗传。研究结果为揭示鸡脂肪肝发病机制和抗病育种提供依据。