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Comprehensive characterization of DNA methylation changes in Fuchs endothelial corneal dystrophy

View Article: PubMed Central - PubMed

ABSTRACT

Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unknown. Here, we report on and compare the DNA methylation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array. We show that DNA methylation profiles are distinct between control and FECD samples. Differentially methylated probes (10,961) were identified in the FECD samples compared with the control samples, with the majority of probes being hypermethylated in the FECD samples. Genes containing differentially methylated sites were disproportionately annotated to ontological categories involving cytoskeletal organization, ion transport, hematopoetic cell differentiation, and cellular metabolism. Our results suggest that altered DNA methylation patterns may contribute to loss of corneal transparency in FECD through a global accumulation of sporadic DNA methylation changes in genes critical to basic CE biological processes.

No MeSH data available.


Number of differentially methylated probes between FECD and control samples (P < 0.05), grouped by the targeted genomic regions.
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pone.0175112.g003: Number of differentially methylated probes between FECD and control samples (P < 0.05), grouped by the targeted genomic regions.

Mentions: We identified a total of 10,961 differentially methylated probes in the FECD samples compared with the control samples (FDR = 0.01, Fig 3). A majority of these probes (6,430; 59%) were hypermethylated in the FECD samples, while 4,531 (41%) were hypomethylated in the FECD samples (Fig 3). Of these, 5,747 probes were located in either gene promoters or gene bodies, while 89 probes were located in intronic gene regions (Fig 3). Notably, most of the differential DNA methylation occurred at probes that are annotated to intergenic regions (Fig 3). Furthermore, no probes were significantly differentially methylated with respect to age or sex in the framework of the linear model (FDR = 0.1), further suggesting that these are not major drivers of DNA methylation differences observed in FECD patients.


Comprehensive characterization of DNA methylation changes in Fuchs endothelial corneal dystrophy
Number of differentially methylated probes between FECD and control samples (P < 0.05), grouped by the targeted genomic regions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383226&req=5

pone.0175112.g003: Number of differentially methylated probes between FECD and control samples (P < 0.05), grouped by the targeted genomic regions.
Mentions: We identified a total of 10,961 differentially methylated probes in the FECD samples compared with the control samples (FDR = 0.01, Fig 3). A majority of these probes (6,430; 59%) were hypermethylated in the FECD samples, while 4,531 (41%) were hypomethylated in the FECD samples (Fig 3). Of these, 5,747 probes were located in either gene promoters or gene bodies, while 89 probes were located in intronic gene regions (Fig 3). Notably, most of the differential DNA methylation occurred at probes that are annotated to intergenic regions (Fig 3). Furthermore, no probes were significantly differentially methylated with respect to age or sex in the framework of the linear model (FDR = 0.1), further suggesting that these are not major drivers of DNA methylation differences observed in FECD patients.

View Article: PubMed Central - PubMed

ABSTRACT

Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unknown. Here, we report on and compare the DNA methylation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array. We show that DNA methylation profiles are distinct between control and FECD samples. Differentially methylated probes (10,961) were identified in the FECD samples compared with the control samples, with the majority of probes being hypermethylated in the FECD samples. Genes containing differentially methylated sites were disproportionately annotated to ontological categories involving cytoskeletal organization, ion transport, hematopoetic cell differentiation, and cellular metabolism. Our results suggest that altered DNA methylation patterns may contribute to loss of corneal transparency in FECD through a global accumulation of sporadic DNA methylation changes in genes critical to basic CE biological processes.

No MeSH data available.