Bioinformatics Seminars

Current Bioinformatics Seminar

21 August 2018

Reconstructing haplotyped methylomes with long-read sequencing for fine dissection of imprinting in mice

Quentin Gouil
WEHI Molecular Medicine

Asymmetric expression patterns between the two parental alleles are critical for development of the mammalian embryo. This process known as imprinting involves differential DNA methylation of the parental genomes. We sequence mouse embryonic placental tissue from reciprocal crosses on the Oxford Nanopore MinION and PromethION platforms, and exploit the long reads to determine both haplotype and CpG methylation levels. Comparison with matched Reduced-Representation Bisulfite Sequencing data confirms the accuracy of the methylation calls, and highlights the improvement in haplotyping conferred by the longer reads. We successfully identify known imprinting control regions and refine their genomic coordinates. Combining de novo differential methylation calling with allele-specific RNA-seq also identifies new correlations between monoallelically expressed genes and allele-specific methylation. The approach we developed to reconstruct haploytped methylome is simpler, cheaper and more powerful than short-read techniques, allowing a greater resolution in the investigation of epigenetic regulation.

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