Confounding by Repetitive Elements and CpG Islands Does Not Explain the Association between Hypomethylation and Genomic Instability

R Alan Harris,Aleksandar Milosavljevic,Jian Li,Anna Gambin,Margaret A Goodell,Ankita Patel,Tomasz Gambin,Chad Shaw,Lisa D White,Mira Jeong,Sau Wai Cheung,James R Lupski,Sung-Hae Kang,A Craig Chinault,Cristian Coarfa,Gregory M Cooper

doi:10.1371/journal.pgen.1003333

Abstract

Confounding by Repetitive Elements and CpG Islands Does Not Explain the Association between Hypomethylation and Genomic Instability

Highlights

We would first like to point out that the goal of our study was not to ignore potential relevance of these other factors— such as repetitive elements and CpG islands—but instead to broaden the scope of inquiry to examine possible additional explanatory power of hypomethylation
Watson et al argue that the association we reported between hypomethylation of genomic DNA—determined from sperm methylomes [3]—and the density of copy number variants (CNVs) can be explained by a combined confounding effect of known correlates of CNVs, namely repetitive elements and CpG islands
We first asked if the variables brought up by Watson et al (LINE, SINE, LTR, Satellite, and CpG island content) individually or in combination explain the association between hypomethylation and CNV counts within 100-Kbp windows tiling the genome

Summary

Introduction

Watson et al argue that the association we reported between hypomethylation of genomic DNA—determined from sperm methylomes [3]—and the density of CNVs can be explained by a combined confounding effect of known correlates of CNVs, namely repetitive elements and CpG islands. We would first like to point out that the goal of our study was not to ignore potential relevance of these other factors— such as repetitive elements and CpG islands—but instead to broaden the scope of inquiry to examine possible additional explanatory power of hypomethylation.

Objectives

Results

Conclusion