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Nat Genet. 2018 Nov;50(11):1542-1552. doi: 10.1038/s41588-018-0232-7. Epub 2018 Oct 22.

Insights into imprinting from parent-of-origin phased methylomes and transcriptomes.

Author information

1
deCODE genetics/AMGEN, Reykjavik, Iceland.
2
Cambridge Epigenetix, Cambridge, UK.
3
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
4
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
5
Landspitali University Hospital, Reykjavik, Iceland.
6
Icelandic Medical Center (Laeknasetrid) Laboratory in Mjodd (RAM), Reykjavik, Iceland.
7
Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.
8
Department of Clinical Biochemistry, The National University Hospital of Iceland, Reykjavik, Iceland.
9
School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
10
deCODE genetics/AMGEN, Reykjavik, Iceland. simon.stacey@decode.is.
11
deCODE genetics/AMGEN, Reykjavik, Iceland. kari.stefansson@decode.is.
12
Faculty of Medicine, University of Iceland, Reykjavik, Iceland. kari.stefansson@decode.is.

Abstract

Imprinting is the preferential expression of one parental allele over the other. It is controlled primarily through differential methylation of cytosine at CpG dinucleotides. Here we combine 285 methylomes and 11,617 transcriptomes from peripheral blood samples with parent-of-origin phased haplotypes, to produce a new map of imprinted methylation and gene expression patterns across the human genome. We demonstrate how imprinted methylation is a continuous rather than a binary characteristic. We describe at high resolution the parent-of-origin methylation pattern at the 15q11.2 Prader-Willi/Angelman syndrome locus, with nearly confluent stochastic paternal methylation punctuated by 'spikes' of maternal methylation. We find examples of polymorphic imprinted methylation unrelated (at VTRNA2-1 and PARD6G) or related (at CHRNE) to nearby SNP genotypes. We observe RNA isoform-specific imprinted expression patterns suggestive of a methylation-sensitive transcriptional elongation block. Finally, we gain new insights into parent-of-origin-specific effects on phenotypes at the DLK1/MEG3 and GNAS loci.

PMID:
30349119
DOI:
10.1038/s41588-018-0232-7

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