Abstract
The inheritance of DNA methylation patterns is a popular theory to explain the influence of parental genetic and environmental factors on the phenotype of their offspring but few studies have examined this relationship in humans. Using 120 paired maternal-umbilical cord blood samples randomly selected from a prospective birth cohort in Bangladesh, we quantified DNA methylation by pyrosequencing seven CpG positions in the promoter region of p16, four CpG positions in the promoter region of p53, LINE-1 and Alu. Positive correlations were observed between maternal and umbilical cord blood at p16, LINE-1, and Alu but not p53. Multiple linear regression models observed a significant association between maternal and umbilical cord blood at LINE-1 and Alu (LINE-1: β = 0.63, p<0.0001; Alu: β = 0.28, p = 0.009). After adjusting for multiple comparisons, maternal methylation of p16 at position 4 significantly predicted methylation at the same position in umbilical cord blood (β = 0.43, p = <0.0001). These models explained 48%, 5% and 16% of the observed variability in umbilical cord %5mC for LINE-1, Alu and p16 at position 4, respectively. These results suggest that DNA methylation in maternal blood was correlated with her offspring at LINE-1, Alu, and p16 but not p53. Additional studies are needed to confirm whether these observed associations were due to the inheritance of epigenetic events or the shared environment between mother and fetus. Future studies should also use a multi-generational family-based design that would quantify both maternal and paternal contributions to DNA methylation in offspring across more than one generation.
Highlights
DNA methylation is an epigenetic modification that involves the covalent addition of a methyl group to a cytosine at the 59-position of a CpG dinucleotide [1]
To better understand the relationship of epigenetic patterns in parent-offspring pairs, we evaluated DNA methylation patterns in 120 paired maternal-child samples collected in a prospective reproductive health study recruited in Bangladesh
Paired t-tests detected very slight differences in %5mC between maternal and umbilical cord blood with umbilical cord blood containing, on average, 0.5% (p = 0.007) more methylated cytosines at LINE-1 compared to maternal blood
Summary
DNA methylation is an epigenetic modification that involves the covalent addition of a methyl group to a cytosine at the 59-position of a CpG dinucleotide [1]. CpG dinucleotides are clustered in the promoter regions of genes [2] and in highly repeated elements such as long interspersed nucleotide elements (LINE-1) and Alu [3,4]. The CpG dinucleotides in these repeated elements are typically heavily methylated in order to silence their expression. They are transposable, that is, expression can lead to insertion into other genomic regions which can result in gene silencing [5,6]. These interspersed repetitive elements may serve as surrogate markers for global DNA methylation [7]. Global DNA hypomethylation is associated with genomic instability and gene specific hypermethylation is associated with gene silencing [11,12]
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