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Reassessment of weak parent-of-origin expression bias shows it rarely exists outside of known imprinted regions

Published version
Peer-reviewed

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Authors

Ferguson-Smith, Anne C  ORCID logo  https://orcid.org/0000-0002-7608-5894

Abstract

In mouse and human, genes subjected to genomic imprinting have been shown to function in development, behaviour, and post-natal adaptations. Failure to correctly imprint genes in human is associated with developmental syndromes, adaptive and metabolic disorders during life as well as numerous forms of cancer. In recent years researchers have turned to RNA-seq technologies applied to reciprocal hybrid strains of mice to identify novel imprinted genes, causing a 3-fold increase in genes reported as having a parental origin specific expression bias. The functional relevance of parental origin-specific expression bias is not fully appreciated especially since many are reported with only minimal parental bias (e.g. 51:49). Here we present an in-depth meta-analysis of previously generated RNA-seq data and show that the methods used to generate and analyse libraries greatly influence the calling of allele-specific expression. Validation experiments show that most novel genes called with parental-origin specific allelic bias are artefactual, with the mouse strain contributing a larger effect on expression biases than parental origin. Of the weak novel genes that do validate, most are located at the periphery of known imprinted domains, suggesting they may be affected by local allele- and tissue-specific conformation. Together these findings highlight the need for robust tools, definitions, and validation of putative imprinted genes to provide meaningful information within imprinting databases and to understand the functional and mechanistic implications of the process

Description

Peer reviewed: True

Keywords

epigenetics, gene expression, genetics, genomics, imprinting, mouse, Humans, Animals, Mice, Gene Expression, Genomic Imprinting, Gene Expression Profiling, Alleles, DNA Methylation

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

Publisher

eLife Sciences Publications Ltd
Sponsorship
Medical Research Council (MR/R009791/1)
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