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Transgenerational Epigenetic and Phenotypic Inheritance Across Five Generations in Sheep

ABSTRACT: Despite two extensive reprogramming events during early embryogenesis and game-togenesis, epigenetic information can be passed to the next generations, which consti-tutes transgenerational epigenetic inheritance of phenotypes. Considering its utmost importance, there have been few studies focused on the transgenerational effects of di-etary interventions, such as methionine supplementation, in livestock. Using whole-genome bisulfite sequencing, we implemented a single-base resolution differen-tial methylation analysis for the F3 and F4 descendants of control vs. methio-nine-supplemented F0 twin-pair rams. Based on the results of our previous study on F0, F1, and F2 generations, we compared current results of 2,981 and 1,726 differen-tially methylated cytosines (DMCs) as well as 798 and 553 unique differentially meth-ylated genes (DMGs) in F3 and F4, respectively. We identified 41 DMGs that exhibited transgenerational epigenetic inheritance (TEI-DMGs) across four generations and 11 TEI-DMGs across five generations. Finally, we estimated the effect size of F0 diet group on F3 and F4 growth and fertility-related phenotypes, providing evidence for transgenerational effects of diet group accompanying inherited differentially methyl-ated genes. Here, for the first time using gene-level and phenotypic data, we demon-strate that a moderate dietary intervention can exert long-lasting transgenerational effects on offspring phenotypes extending beyond the F2 generation in sheep.

ORGANISM(S): Ovis aries

PROVIDER: GSE301579 | GEO | 2025/07/16

REPOSITORIES: GEO

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