Intergenerational genomic DNA methylation patterns in mouse hybrid strains

• Published in: Genome biology Vol. 15; no. 5; p. R68
• Main Authors: Orozco, Luz D, Rubbi, Liudmilla, Martin, Lisa J, Fang, Fang, Hormozdiari, Farhad, Che, Nam, Smith, Andrew D, Lusis, Aldons J, Pellegrini, Matteo
• Format: Journal Article
• Language: English
• Published: London BioMed Central 30.04.2014
• Subjects: Animal Genetics and Genomics; animal models; Animals; Bioinformatics; Biomedical and Life Sciences; chromosomes; Chromosomes, Mammalian; Crosses, Genetic; DNA; DNA Methylation; epigenetics; Evolutionary Biology; Female; females; gender differences; gene expression; gene silencing; genes; genetic traits; genetic variation; Genome; Genomic Imprinting; human diseases; Human Genetics; Hybridization, Genetic; hybrids; Life Sciences; liver; Liver - metabolism; Male; males; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Microbial Genetics and Genomics; microRNA; MicroRNAs - metabolism; Molecular Sequence Data; Plant Genetics and Genomics; Sequence Analysis, DNA - methods; Sex Characteristics; Average Methylation Level; Bisulfite Sequencing; Reduce Representation Bisulfite Sequencing; Methylation Level; Imprint Gene
• ISSN: 1474-760X; 1465-6906; 1474-760X; 1465-6914
• DOI: 10.1186/gb-2014-15-5-r68

Background DNA methylation is a contributing factor to both rare and common human diseases, and plays a major role in development and gene silencing. While the variation of DNA methylation among individuals has been partially characterized, the degree to which methylation patterns are preserved across generations is still poorly understood. To determine the extent of methylation differences between two generations of mice we examined DNA methylation patterns in the livers of eight parental and F1 mice from C57BL/6J and DBA/2J mouse strains using bisulfite sequencing. Results We find a large proportion of reproducible methylation differences between C57BL/6J and DBA/2J chromosomes in CpGs, which are highly heritable between parent and F1 mice. We also find sex differences in methylation levels in 396 genes, and 11% of these are differentially expressed between females and males. Using a recently developed approach to identify allelically methylated regions independently of genotypic differences, we identify 112 novel putative imprinted genes and microRNAs, and validate imprinting at the RNA level in 10 of these genes. Conclusions The majority of DNA methylation differences among individuals are associated with genetic differences, and a much smaller proportion of these epigenetic differences are due to sex, imprinting or stochastic intergenerational effects. Epigenetic differences can be a determining factor in heritable traits and should be considered in association studies for molecular and clinical traits, as we observed that methylation differences in the mouse model are highly heritable and can have functional consequences on molecular traits such as gene expression.