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富亮氨酸重复激酶2(Lrrk2)基因与家族性及散发性帕金森病(Parkinson’s disease,PD)密切相关,但其作用机制仍不十分清楚.本文以单核苷酸多态性(single nucleotide polymorphism,SNP)为切入点,对其调控机制进行研究.以近交系C57BL/6J(B6)和DBA/2J(D2)小鼠杂交1代小鼠为实验动物,借助基因表达数量性状基因座(expression quantitative trait loci,eQTL)分析技术,结合等位基因特异性表达(allele specific expression difference,ASE)技术,验证帕金森病相关基因Lrrk2的顺式调控机制.eQTL分析显示,Lrrk2基因所在的位置有1个具有显著统计学意义(LRS值≥20)的顺式调节基因座.针对Lrrk2基因外显子区域错意突变SNP的ASE分析得出:rs50098646位点在cDNA水平上G∶A两碱基比值偏离1∶1,与gDNA水平中G∶A两碱基比值差异显著(P<0.01),表达受顺式作用调节.本研究结果表明,Lrrk2基因的表达受到顺式作用的调控.
The gene of Lrrk2 is closely related to familial and sporadic Parkinson’s disease (PD), but its mechanism of action remains unclear.In this paper, single nucleotide polymorphism (single nucleotide polymorphism (B6) and DBA / 2J (D2) inbred mice were used as experimental animals, and the relationship between quantitative trait locus (eQTL), combined with allele specific expression difference (ASE), was used to validate the cis-regulatory mechanism of Lrrk2 gene in Parkinson’s disease.EQTL analysis showed that the location of Lrrk2 gene was 1 cis-regulated loci with significant statistical significance (LRS value≥20). ASE analysis of missense mutation SNPs in the exon region of Lrrk2 gene revealed that rs50098646 locus was at G: A two bases at the cDNA level The ratio deviated from 1: 1, which was significantly different from the ratio of G: A two bases in gDNA level (P <0.01), and the expression was regulated by cis-acting.The results of this study indicated that the expression of Lrrk2 gene was regulated by cis-acting.