Title: Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles
Authors: Souren, Nicole Yp ×
Lutsik, Pavlo
Gasparoni, Gilles
Tierling, Sascha
Gries, Jasmin
Riemenschneider, Matthias
Fryns, Jean-Pierre
Derom, Cathérine
Zeegers, Maurice P
Walter, Jörn #
Issue Date: May-2013
Series Title: Genome biology vol:14 issue:5 pages:R44-R44
Abstract: BACKGROUND: Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes. RESULTS: Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean beta-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remained in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences. CONCLUSIONS: Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies.
ISSN: 1465-6914
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Clinical Genetics
× corresponding author
# (joint) last author

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