小鼠眼血管内皮生长因子家族基因相关性研究

Study of gene correlation between endothelial growth factor family in mouse eye

目的比较小鼠眼VEGF家族VEGFA、VEGFB和VEGFC之间功能和作用途径的异同。方法利用Genenetwork数据库中BXD小鼠眼基因数据作为模板,采用基因表达水平、基因间比较、相关基因间的比较、基因表达数量性状基因座(eQTL)等多种方法和统计策略,对BXD重组小鼠近交系群体的眼全基因组表达谱数据中VEGF家族VEGFA、VEGFB和VEGFC的分子通路或潜在功能的异同进行比较和研究。结果矩阵比较结果显示,VEGFC的2个探针之间呈强正相关(r=0.732,P<0.01);VEGFA 1420909与VEGFC 1440739、VEGFA 1451959与VEGFB 1451803、VEGFC 1419417与其他5个基因、VEGFA 1451959与VEGFC 1419417/VEGFC 1439766、VEGFB 1451803与VEGFC 1439766均呈弱相关性(P<0.05);VEGFA 1420909与除VEGFC 1440739之外的4个基因、VEGFA 1451959与VEGFC 1440739、VEGFB 1451803与VEGFA 1420909/VEGFC 1419417/VEGFC 1440739之间无相关性(P>0.05)。在VEGF各基因的相关Top50基因的对比分析中,BXD小鼠眼中VEGFA、VEGFB和VEGFC之间除个别相关基因存在弱关联外,其他大部分基因并不存在较显著的相关性。eQTL分析结果显示,VEGF基因各探针中eQTL分别定位于不同的染色体上。结论小鼠眼VEGF家族中VEGFA、VEGFB和VEGFC之间表达水平和正负相关性各不相同,这些基因可能通过不同的途径发挥其作用。

Objective To compare the function and action pathways of VEGFA,VEGFB and VEGFC in VEGF family of mouse eye.Methods Using the BXD mouse gene data in Genenetwork database as template to compare and study the similarities and differences of VEGFA,VEGFB and VEGFC molecular pathways or potential functions in the whole genome expression spectrum of BXD recombinant mouse inbred line population,with multiple analytical methods and statistical strategies were used,such as gene expression level,target genes comparison,top genes comparison associated to target genes,expression Quantitative Trait Loci(eQTL).Results Matrix comparison showed strong positive correlation between two probes of VEGFC(r=0.732,P<0.01),weak correlation between VEGFA 1420909 and VEGFC 1440739,VEGFA 1451959 and VEGFC 1451803,VEGFC 1419417959 and VEGFC 1439766,VEGFC 1451803 and VEGFC 1439766(P<0.05);there was no correlation between VEGFA 1420909 and four other genes except VEGFC 1440739,VEGFA 1451959 and VEGFC 1440739,VEGFB 1451803 and VEGFA 1420909/VEGFC 1419417/VEGFC 1440739(P>0.05).In the comparative analysis of the relevant Top50 genes of each VEGF gene,most of the genes in BXD mouse were not significantly correlated with VEGFA,VEGFB and VEGFC except for the weak association of individual related genes.The results of eQTL analysis showed that each probe of VEGF gene was located on different chromosomes.Conclusions The expression levels and positive and negative correlations of VEGFA,VEGFB and VEGFC were different in the VEGF family of mouse eye,suggesting that these genes may play their role through different pathways.