Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation

التفاصيل البيبلوغرافية
العنوان: Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation
المؤلفون: Busche, Stephan, Shao, Xiaojian, Caron, Maxime, Kwan, Tony, Allum, Fiona, Cheung, Warren, Ge, Bing, Westfall, Susan, Simon, Marie-Michelle, The Multiple Tissue Human Expression Resource, Barrett, Amy, Bell, Jordana, McCarthy, Mark, Deloukas, Panos, Blanchette, Mathieu, Bourque, Guillaume, Spector, Timothy, Lathrop, Mark, Pastinen, Tomi, Grundberg, Elin
بيانات النشر: BioMed Central Ltd.
سنة النشر: 2015
المجموعة: BioMed Central
مصطلحات موضوعية: Adipose, Blood, CpH methylation, Differentially methylated region (DMR), DNA methylation, Enhancer, Environment, Population, Twins, Whole-genome bisulfite sequencing (WGBS)
الوصف: Background CpG methylation variation is involved in human trait formation and disease susceptibility. Analyses within populations have been biased towards CpG-dense regions through the application of targeted arrays. We generate whole-genome bisulfite sequencing data for approximately 30 adipose and blood samples from monozygotic and dizygotic twins for the characterization of non-genetic and genetic effects at single-site resolution. Results Purely invariable CpGs display a bimodal distribution with enrichment of unmethylated CpGs and depletion of fully methylated CpGs in promoter and enhancer regions. Population-variable CpGs account for approximately 15–20 % of total CpGs per tissue, are enriched in enhancer-associated regions and depleted in promoters, and single nucleotide polymorphisms at CpGs are a frequent confounder of extreme methylation variation. Differential methylation is primarily non-genetic in origin, with non-shared environment accounting for most of the variance. These non-genetic effects are mainly tissue-specific. Tobacco smoking is associated with differential methylation in blood with no evidence of this exposure impacting cell counts. Opposite to non-genetic effects, genetic effects of CpG methylation are shared across tissues and thus limit inter-tissue epigenetic drift. CpH methylation is rare, and shows similar characteristics of variation patterns as CpGs. Conclusions Our study highlights the utility of low pass whole-genome bisulfite sequencing in identifying methylome variation beyond promoter regions, and suggests that targeting the population dynamic methylome of tissues requires assessment of understudied intergenic CpGs distal to gene promoters to reveal the full extent of inter-individual variation.
نوع الوثيقة: report
اللغة: English
العلاقة: http://genomebiology.com/2015/16/1/290Test
الإتاحة: http://genomebiology.com/2015/16/1/290Test
حقوق: Copyright 2015 Busche et al.
رقم الانضمام: edsbas.3816D4BA
قاعدة البيانات: BASE