Genetic determinism of sperm DNA methylation in French Holstein cattle
Résumé
Methylation quantitative trait loci (meQTL) are genetic variants that influence DNA methylation. In cattle, little
is known about the genetic determinism of DNA methylation, either at the level of individual methylation sites
(CpGs) or on a global scale. In this study, we investigated the sperm methylome of 262 Holstein bulls obtained
by reduced representation bisulfite sequencing. After filtering out CpGs without individual variability or co-localizing
with SNPs, we performed sequence-based GWAS of three groups of methylation phenotypes: (1) principal
component scores of the most variable CpG sites, (2) average DNA methylation rate for genomic regions (e.g.
whole chromosome, gene, promoter), and (3) DNA methylation rates of individual CpG sites. We then examined
the SNPs significantly associated with CpG methylation (-log10(P) > 7.3) and classified them according to their
proximity to the CpG, i.e. cis (<1 Mb), cis long-range (>1Mb, on the same chromosome), and trans (on different
chromosomes). We found meQTLs for all phenotypic categories, most of which had cis-regulatory effects. In
addition, our study identified candidate genes involved in methylation pathways. Taken together, these results
demonstrate a genetic determinism of DNA methylation in cattle and thus an interplay between genetic variation
and epigenetic regulation. CF is recipient of a CIFRE PhD grant from ANRT and APIS-GENE. This work was
part of the POLYPHEME project funded by ANR (ANR-21-CE20-0021) and APIS-GENE.
Domaines
Génétique animaleOrigine | Fichiers produits par l'(les) auteur(s) |
---|