On 2015 Dec 07, Aleksandar Milosavljevic commented:

This recently published paper provides independent validation of the association of hypomentylation and genomic instability: http://www-ncbi-nlm-nih-g...

Quoting from the discussion section of the paper: "In addition, we found two lines of evidence associating NAHR breakpoints with hypomethylation: lower frequency of C to T SNPs in CpG motifs and an enrichment with demethylated regions in sperm. NAHR breakpoints have been previously suggested to be associated with hypomethylation [ref. 41]; however, the findings were debated with the notion that technical variability may explain the association [ref. 42]. In our SNP aggregation analysis, we used roughly 70% of the human genome sequence where SNPs could be confidently determined. Demethylated regions in sperm used in our study were determined from comparative analysis of methylation profiles that are directly inferred from whole-genome bisulfide sequencing in sperm and embryonic cell. Such comparative analysis is not likely to be influenced by technical artefacts. We, thus, state that the observed association of NAHR breakpoints with hypomethylation is not artefactual, although not as strong as suggested in ref. 41. It also corroborates association of NAHR breakpoints with open chromatin."

On 2014 Mar 24, Andrew Sharp commented:

Readers of this article should be aware of a Viewpoints piece we published that raises major concerns about the validity of the conclusions that there is a link between CNV and hypomethylation, see: http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003332

A counter-point piece was then published by the original authors here: http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003333

Interested readers should also look at a thorough discussion that details the problems in the original analysis methods that is shown in the ensuing comments thread here: http://www.plosgenetics.org/annotation/listThread.action?root=62329

On 2014 Mar 24, Andrew Sharp commented:

Readers of this article should be aware of a Viewpoints piece we published that raises major concerns about the validity of the conclusions that there is a link between CNV and hypomethylation, see: http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003332

A counter-point piece was then published by the original authors here: http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003333

Interested readers should also look at a thorough discussion that details the problems in the original analysis methods that is shown in the ensuing comments thread here: http://www.plosgenetics.org/annotation/listThread.action?root=62329

On 2015 Dec 07, Aleksandar Milosavljevic commented:

This recently published paper provides independent validation of the association of hypomentylation and genomic instability: http://www-ncbi-nlm-nih-g...

Quoting from the discussion section of the paper: "In addition, we found two lines of evidence associating NAHR breakpoints with hypomethylation: lower frequency of C to T SNPs in CpG motifs and an enrichment with demethylated regions in sperm. NAHR breakpoints have been previously suggested to be associated with hypomethylation [ref. 41]; however, the findings were debated with the notion that technical variability may explain the association [ref. 42]. In our SNP aggregation analysis, we used roughly 70% of the human genome sequence where SNPs could be confidently determined. Demethylated regions in sperm used in our study were determined from comparative analysis of methylation profiles that are directly inferred from whole-genome bisulfide sequencing in sperm and embryonic cell. Such comparative analysis is not likely to be influenced by technical artefacts. We, thus, state that the observed association of NAHR breakpoints with hypomethylation is not artefactual, although not as strong as suggested in ref. 41. It also corroborates association of NAHR breakpoints with open chromatin."