DNA methylation correlation structure of chromosome 21 in Down syndrome.

Abstract

DNA methylation studies usually focus on the groups of CpG sites. Neighbouring CpG sites are analyzed together due to their group behaviour. However, this approach ignores the possible interaction between more distant CpG sites. In this work, we investigate the complete methylation correlation structure of chromosome 21. Two data sets were used for the correlation analysis, smaller data set with methylation measurements from Down syndrome patients and their family members and larger data set with healthy subjects. This allowed us to examine the general properties of the methylation correlation structure as well as its modifications in presence of an extra copy of the chromosome. We observed that the CpG sites work in small highly correlated groups. While some groups coincided with CpG islands, other groups contained CpG sites scattered across the whole chromosome. Groups of highly correlated CpG sites remained preserved in the case of Down syndrome. Moreover, the methylome of a Down syndrome patient had newly formed correlations between CpG sites suggesting that the methylation correlation structure in Down syndrome is stronger than in case of an unaffected individual.