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Human placental-specific epipolymorphism and its association with adverse pregnancy outcomes.

Yuen, RK; Avila, L; Peñaherrera, MS; von Dadelszen, P; Lefebvre, L; Kobor, MS; Robinson, WP (2009) Human placental-specific epipolymorphism and its association with adverse pregnancy outcomes. PLoS One, 4 (10). ISSN 1932-6203
SGUL Authors: von Dadelszen, Peter

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Interindividual variation in DNA-methylation level is widespread in the human genome, despite its critical role in regulating gene expression. The nature of this variation, including its tissue-specific nature, and the role it may play in human phenotypic variation and disease is still poorly characterized. The placenta plays a critical role in regulating fetal growth and development in ways that have lifelong effects on health. To identify genes with a high degree of interindividual DNA methylation variation in the human placenta, we surveyed the human genome using the Illumina GoldenGate Methylation Cancer panel targeting 1505 CpG sites of 807 genes. While many sites show a continuous pattern of methylation levels, WNT2, TUSC3 and EPHB4 were identified to have a polymorphic "on-or-off" pattern of DNA methylation variation at their promoter region which was confirmed by pyrosequencing. Methylation of these genes can be found in 7%-25% of over 100 placentas tested. The methylation state at the promoter of these genes is concordant with mRNA allelic expression. In three informative cases TUSC3 was observed to be methylated on the maternal allele, and it is thus possible this represents a polymorphically imprinted gene. Furthermore, TUSC3 promoter methylation showed evidence for association with preeclampsia. A biological significance of these methylation allelic polymorphisms (MAPs) to human placental diversity is further implied by their placental specificity and absence in mouse. An extended study of blood suggests that MAPs may also be found in other tissues, implicating their utility for tissue-specific association with complex disorders. The identification of such "epipolymorphism" in other tissues and their use in association studies, should improve our understanding of interindividual phenotypic variability and complex disease susceptibility.

Item Type: Article
Additional Information: © 2009 Yuen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Alleles, Animals, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Genome, Human, Humans, Mice, Phenotype, Placenta, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Pregnancy, Animal, Promoter Regions, Genetic, Placenta, Animals, Humans, Mice, Pregnancy Complications, Pregnancy Outcome, DNA Methylation, Epigenesis, Genetic, CpG Islands, Pregnancy, Pregnancy, Animal, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Alleles, Genome, Human, Female, Promoter Regions, Genetic, General Science & Technology, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: PLoS One
Article Number: e7389
ISSN: 1932-6203
Language: eng
19 October 2009Published
Publisher License: Creative Commons: Attribution 4.0
Project IDFunderFunder ID
GMH-79041Canadian Institutes of Health Research
PubMed ID: 19838307
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