Allele-specific methylation of imprinted genes in fetal cord blood is influenced by cis-acting genetic variants and parental factors

胎儿脐带血中印迹基因的等位基因特异性甲基化受顺式遗传变异和父母因素的影响

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作者:Ramya Potabattula, Marcus Dittrich, Julia Böck, Larissa Haertle, Tobias Müller, Thomas Hahn, Martin Schorsch, Nady El Hajj, Thomas Haaf

Aim

To examine the effects of genetic variation, parental age and BMI on parental allele-specific methylation of imprinted genes in fetal cord blood samples. Methodology: We have developed SNP genotyping and deep bisulphite sequencing assays for six imprinted genes to determine parental allele-specific methylation patterns in diploid somatic tissues.

Conclusion

Our study supports the idea that parental factors can have an impact, although of small effect size, on the epigenome of the next generation, providing an additional layer of complexity to phenotypic diversity.

Results

Multivariate linear regression analyses revealed a negative correlation of paternal age with paternal MEG3 allele methylation in fetal cord blood. Methylation of the maternal PEG3 allele showed a positive correlation with maternal age. Paternal BMI was positively correlated with paternal MEST allele methylation. In addition to parental origin, allele-specific methylation of most imprinted genes was largely dependent on the underlying SNP haplotype.

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