Expression QTL and genetic regulatory network analysis of Col11a1

Previous studies have revealed that the mutation of Col11a1 (collagen, type XI, alpha 1) plays a critical role in the Stickler and Marshall syndrome. However, little is known about the genetic regulatory network for Col11a1 and the Stickler and Marshall syndrome. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Col11a1 expression in the eye of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Col11a1 exhibited much variation in the eye across the BXD RI strains and between the parental strains, C57BL/6J and DBA/2J. Expression QTL (eQTL) mapping showed two microarray probe sets of Col11a1 have highly significant linkage (Likelihood Ratio Statistic) scores. Moreover, the QTL was mapped to within 3 Mb of the location of the gene itself (Col11a1) as a cis-ac ting QTL. Through mapping the joint modulation of Col11a1, we identified 23 transcripts/genes with trans-regulated QTLs close to the location of Col11a1 as downstream genes of Col11a1. Then the gene co-regulatory network analysis was constructed. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as Stickler and Marshall syndrome.