Congenital scolisis may be associated with both of rare mutation and allele-specific methylation

Congenital scoliosis (CS) is a congenital disease that results in anomalous vertebral development. Research indicates that both genetic and environmental factors during pregnancy contribute to the risk of CS development, however, the exact mechanisms underlying CS pathogenesis remain unclear. To address this issue, we have generated both genetic (by exon capture sequencing) and epigenetic (by MeDIP) maps from a CS disease-discordant monozygotic twin pair. We compared the differences in the presence of common and rare SNPs between the twins as well as investigated differences in methylation patterns. Our data indicated that rare mutations are more likely to underlie CS development than common mutations, and that these are also more likely to play a role than do genomic methylation patterns. We did, however, identify a difference in the allele-specific-methylation between the twins in the SVIL gene which has functions in categories relevant to this disease, which raises the possibility of a novel mechanism promoting CS pathogenesis. Overall design: DNA was extracted from peripheral blood of a monozygotic twin pair that was discordant for CS, with T-P affected with CS and T-H non-affected. Followed by MeDIP-seq and exome-seq.