Analysis of Myocilin gene regulatory network using a genetic genomics approach / 中华实验眼科杂志

ABSTRACT

Background The pathogenesis of primary open angle glaucoma(POAG) and high myopia are very complex.To construct the regulatory network of virulence genes and relevant genes that involved in pathogenicity are helpful for reveal of the pathogenesis.Objective The aim of this study was to investigate myocilin(Myoc),a gene that contributes to POAG and high myopia in eyes of BXD Recombinant Inbred(BXD RI)mice and construct the regulatory network of Myoc.Methods The affymetrix microarray system was used to detect the differential expression of Myoc in the eyes of C57BL/6J(B6),DBA/2J(D2) and BXD RI mice.Expression quantitative trait loci (eQTL) mapping was performed to construct the regulatory network of Myoc gene.Results The average expression level of the Myoc gene in the BXD strains was 10.83,and the gene exhibited expression levels ranging from 8.39 in BXD55 mice tol 1.43 in B6 mice.The eQTL mapping for the Myoc gene showed a significant likelihood ratio statistic (LRS) of 21.78.The QTL was mapped in chromosome 2,and Myoc was located on chromosome 1,indicating that the Myoc gene was a trans-acting QTL.Olfml2a was identified to be a candidate upstream gene of Myoc by analysis of bioinformatics.Genetic regulatory network analysis demonstrated that a series of genes associated with Myoc probably played roles in the pathogenesis and development of POAG and high myopia.Conclusions The genetical genomics approach provides a powerful tool for constructing pathways that contribute to complex traits,such as POAG and high myopia.