Genetic regulatory network analysis for Myoc based on genetical genomics approach

Numerous studies have shown that the myocilin gene (MYOC) plays an important role in primary open-angle glaucoma (POAG) and high myopia. However, little is known about the genetic regulatory network. In this study, we combined array analysis and quantitative trait loci (QTL) mapping approaches (genetical genomics) to characterize the expression variation and the regulatory network of Myoc in the eye of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Myoc exhibited much variation in the eye across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Interval mapping results showed that expression quantitative trait loci (eQTL) mapping for Myoc had a significant linkage score (LRS) of 21.775. Moreover, the QTL was mapped in another chromosome of Myoc as a trans-acting QTL. We identified Olfml2a as a candidate upstream gene of Myoc. Gene Ontology (GO) analysis was carried out and the gene co-regulatory network was constructed. These results demonstrate that the genetical genomics approach provides a powerful tool for constructing pathways that contribute to complex traits, such as POAG and high myopia.