Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide DNA methylation profiling of Progeria and Werner syndrome patients

ABSTRACT: DNA methylation gradiently changes with age and is likely to be involved in aging-related processes resulting in phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria Syndrome (HGP) and Werner Syndrome are two premature aging diseases showing features of common aging. Mutations in LMNA and WRN genes were associated to disease onset; however for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing genome-wide DNA methylation profiling of HGP and WS patients. DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was perform according to the manufacturer's recommendation for Illumina Infinium Assay. Effective bisulphite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite converted DNA were used to hybridize on Infinium HumanMethylation 450 BeadChip, following Illumina Infinium HD Methylation protocol. Chip analysis was performed using Illumina HiScan SQ fluorescent scanner. The intensities of the images are extracted using GenomeStudio (2010.3) Methylation module (1.8.5) software. Methylation score of each CpG is represented as beta value. Naive B-cells and peripheral blood mononuclear cells were analyzed to correct for the epigenetic effects of the Epstein-Barr virus immortalization (lymphoblastoid cell lines) and cell composition of the samples, respectively.

ORGANISM(S): Homo sapiens

SUBMITTER: Antonio Gómez

PROVIDER: E-GEOD-42865 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome.

Heyn Holger H Moran Sebastian S Esteller Manel M

Epigenetics 20121220 1

DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed ...[more]

PMID: 23257959

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Project description:Human aging implies many phenotypic modifications and an increased susceptibility to many common diseases, phenomena that cannot be fully explained by the constrained genetic setting. An alternative pathway that could explain the age-associated alterations is epigenetic drifts. To address this issue, we performed Whole Genome Bisulfite Sequencing (WGBS) of a newborn and of a centenarian. The centenarian DNA exhibited a significant loss in DNA methylation and a poor correlation in the methylation status of neighboring CpGs throughout the genome. From a gene-regulatory region standpoint, we observed that the DNA hypomethylation events occurred mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. Most importantly, we extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray. The 450K DNA methylation approach enabled validation of the WGBS data and revealed additional age-related DNA methylation events. Interestingly, we also observed the DNA methylation fingerprint characteristic of a healthy aged cell in samples from patients with premature-aging disorders such as Hutchinson-Gilford progeria and Werner syndrome. Overall, we suggest that defects in the physiological DNA methylation profile contribute to the process of human aging. As the disease associated cells were immortalized B cells, the effect of EBV immortalization was determined in advance to the study using immortalized and naive B cells. DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was perform according to the manufacturer's recommendation for Illumina Infinium Assay. Effective bisulphite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite converted DNA were used to hybridize on Infinium HumanMethylation 450 BeadChip, following Illumina Infinium HD Methylation protocol. Chip analysis was performed using Illumina HiScan SQ fluorescent scanner. The intensities of the images are extracted using GenomeStudio (2010.3) Methylation module (1.8.5) software. Methylation score of each CpG is represented as beta value.

Dataset Information

Genome-wide DNA methylation profiling of Progeria and Werner syndrome patients

Publications

Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome.

Similar Datasets

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