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Genome-wide analysis of DNA methylation associated with HIV infection based on a pair of monozygotic twins.

ABSTRACT: Alteration of DNA methylation in mammalian cells could be elicited by many factors, including viral infections [1]. HIV has shown the ability to interact with host cellular factors to change the methylation status of some genes [2], [3], [4]. However, the change of the DNA methylation associated with HIV infection based on the whole genome has not been well illustrated. In this study, a unique pair of monozygotic twins was recruited: one of the twins was infected with HIV without further anti-retroviral therapy while the other one was healthy, which could be considered as a relatively ideal model for profiling the alterations of DNA methylation associated with HIV infection. Therefore, using methylated DNA immunoprecipitation-microarray method (MeDIP-microarray), we found the increased DNA methylation level in peripheral blood mononuclear cells from HIV infected twin compared to her normal sibling. Moreover, several distinguished differential methylation regions (DMRs) in HIV infected twin worth further study. The raw data has been deposited in Gene Expression Omnibus (GEO) datasets with reference number GSE68028.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4664672 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Genome-wide analysis of DNA methylation associated with HIV infection based on a pair of monozygotic twins.

Zhang Yinfeng Y Li Sai-Kam SK Tsui Stephen Kwok-Wing SK

Genomics data 20150730

Alteration of DNA methylation in mammalian cells could be elicited by many factors, including viral infections [1]. HIV has shown the ability to interact with host cellular factors to change the methylation status of some genes [2], [3], [4]. However, the change of the DNA methylation associated with HIV infection based on the whole genome has not been well illustrated. In this study, a unique pair of monozygotic twins was recruited: one of the twins was infected with HIV without further anti-re ...[more]

PMID: 26697319

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Project description:BACKGROUND:DNA methylation arrays are widely used in epigenome-wide association studies and methylation quantitative trait locus (mQTL) studies. Here, we performed the first genome-wide analysis of monozygotic (MZ) twin correlations and mQTLs on data obtained with the Illumina MethylationEPIC BeadChip (EPIC array) and compared the performance of the EPIC array to the Illumina HumanMethylation450 BeadChip (HM450 array) for buccal-derived DNA. RESULTS:Good-quality EPIC data were obtained for 102 buccal-derived DNA samples from 49 MZ twin pairs (mean age?=?7.5 years, range?=?1-10). Differences between MZ twins in the cellular content of buccal swabs were a major driver for differences in their DNA methylation profiles, highlighting the importance to adjust for cellular composition in DNA methylation studies of buccal-derived DNA. After adjusting for cellular composition, the genome-wide mean correlation (r) between MZ twins was 0.21 for the EPIC array, and cis mQTL analysis in 84 twins identified 1,296,323 significant associations (FDR 5%), encompassing 33,749 methylation sites and 616,029 genetic variants. MZ twin correlations were slightly larger (p?<?2.2?×?10-16) for novel EPIC probes (N?=?383,066, mean r?=?0.22) compared to probes that are also present on HM450 (N?=?406,822, mean r?=?0.20). In line with this observation, a larger percentage of novel EPIC probes was associated with genetic variants (novel EPIC probes with significant mQTL 4.7%, HM450 probes with mQTL 3.9%, p?<?2.2?×?10-16). Methylation sites with a large MZ correlation and sites associated with mQTLs were most strongly enriched in epithelial cell DNase I hypersensitive sites (DHSs), enhancers, and histone mark H3K4me3. CONCLUSIONS:We conclude that the contribution of familial factors to individual differences in DNA methylation and the effect of mQTLs are larger for novel EPIC probes, especially those within regulatory elements connected to active regions specific to the investigated tissue.

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Genome-wide analysis of DNA methylation associated with HIV infection based on a pair of monozygotic twins.

Publications

Genome-wide analysis of DNA methylation associated with HIV infection based on a pair of monozygotic twins.

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