Genetic and epigenetic variation among inbred mouse littermates: Identification of inter-individual differentially methylated regions

Oey, Harald, Isbel, Luke, Hickey, Peter, Ebaid, Basant and Whitelaw, Emma (2015) Genetic and epigenetic variation among inbred mouse littermates: Identification of inter-individual differentially methylated regions. Epigenetics and Chromatin, 8 54: . doi:10.1186/s13072-015-0047-z


Author Oey, Harald
Isbel, Luke
Hickey, Peter
Ebaid, Basant
Whitelaw, Emma
Title Genetic and epigenetic variation among inbred mouse littermates: Identification of inter-individual differentially methylated regions
Journal name Epigenetics and Chromatin   Check publisher's open access policy
ISSN 1756-8935
Publication date 2015-12-12
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s13072-015-0047-z
Open Access Status DOI
Volume 8
Issue 54
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2016
Language eng
Formatted abstract
Background: Phenotypic variability among inbred littermates reared in controlled environments remains poorly understood. Metastable epialleles refer to loci that intrinsically behave in this way and a few examples have been described. They display differential methylation in association with differential expression. For example, inbred mice carrying the agouti viable yellow (A vy ) allele show a range of coat colours associated with different DNA methylation states at the locus. The availability of next-generation sequencing, in particular whole genome sequencing of bisulphite converted DNA, allows us, for the first time, to search for metastable epialleles at base pair resolution.

Results: Using whole genome bisulphite sequencing of DNA from the livers of five mice from the A vy colony, we searched for sites at which DNA methylation differed among the mice. A small number of loci, 356, were detected and we call these inter-individual Differentially Methylated Regions, iiDMRs, 55 of which overlap with endogenous retroviral elements (ERVs). Whole genome resequencing of two mice from the colony identified very few differences and these did not occur at or near the iiDMRs. Further work suggested that the majority of ERV iiDMRs are metastable epialleles; the level of methylation was maintained in tissue from other germ layers and the level of mRNA from the neighbouring gene inversely correlated with methylation state. Most iiDMRs that were not overlapping ERV insertions occurred at tissue-specific DMRs and it cannot be ruled out that these are driven by changes in the ratio of cell types in the tissues analysed.

Conclusions: 
Using the most thorough genome-wide profiling technologies for differentially methylated regions, we find very few intrinsically epigenetically variable regions that we term iiDMRs. The most robust of these are at retroviral elements and appear to be metastable epialleles. The non-ERV iiDMRs cannot be described as metastable epialleles at this stage but provide a novel class of variably methylated elements for further study.
Keyword Metastable epiallele
Genetic variation
Inbred mice
DNA methylation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
UQ Diamantina Institute Publications
 
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