Journal
FRONTIERS IN GENETICS
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2020.00348
Keywords
polycystic kidney; DNA methylation; autosomal dominant polycystic kidney disease; reduced representation bisulfite sequencing; epigenetics
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Funding
- PKD Foundation of Australia
- Maurice and Phyllis Paykel Trust
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Autosomal dominant polycystic kidney disease (ADPKD) is a heritable disease characterized by bilateral renal enlargement due to the growth of cysts throughout the kidneys. Inheritance of a disease-causing mutation is required to develop ADPKD, which results in end-stage kidney disease and is associated with a high morbidity. The pathology underlying cyst formation is not well understood. To address this, we have previously shown the global methylome is altered in ADPKD tissue, suggesting a role of DNA methylation in disease-state renal tissue. As cysts are believed to arise independently, we hypothesize that DNA methylation changes vary accordingly. Here we further investigate the role of DNA methylation within independent cysts to characterize key intra-individual changes. We demonstrate that fragments within CpG islands and gene bodies harbor the greatest amount of variation across the ADPKD kidney, while intergenic fragments are comparatively stable. A proportion of variably methylated genes were also differentially methylated in ADPKD tissue. Our data provide evidence that individual molecular mechanisms are operating in the development of each cyst.
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