The effects of age, sex, weight, and breed on canid methylomes

Liudmilla Rubbi, Haoxuan Zhang, Junxi Feng, Christopher He, Patrick Kurnia, Prashansa Ratan, Aakash Tammana, Sabina House, Michael Thompson, Colin Farrell, Sagi Snir, Daniel Stahler, Elaine A. Ostrander, Bridgett M. vonHoldt, Matteo Pellegrini

Research output: Contribution to journalArticlepeer-review

Abstract

Unlike genomes, which are static throughout the lifespan of an organism, DNA methylomes are dynamic. To study these dynamics, we developed quantitative models that measure the effect of multiple factors on DNA methylomes including, age, sex, weight, and genetics. We conducted our study in canids, which prove to be an ideal species to assess epigenetic moderators due to their extreme variability in size and well-characterized genetic structure. We collected buccal swabs from 217 canids (207 domestic dogs and 10 grey wolves) and used targeted bisulphite sequencing to measure methylomes. We also measured genotypes at over one thousand single nucleotide polymorphisms (SNPs). As expected, we found that DNA methylomes are strongly associated with age, enabling the construction of epigenetic clocks. However, we also identify novel associations between methylomes and sex, weight, and sterilization status, leading to accurate models that predict these factors. Methylomes are also affected by genetics, and we observe multiple associations between SNP loci and methylated CpGs. Finally, we show that several factors moderate the relationship between epigenetic ages and real ages, such as body weight, which increases epigenetic ageing. In conclusion, we demonstrate that the plasticity of DNA methylomes is impacted by myriad genetics and physiological factors, and that DNA methylation biomarkers are accurate predictors of age, sex and sterilization status.

Original languageEnglish
JournalEpigenetics
DOIs
StateAccepted/In press - 2022

Bibliographical note

Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • canids
  • DNA methylation
  • dogs
  • epigenetic clock

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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