Genetic determinism of sperm DNA methylation in French Holstein cattle

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Fouéré, Corentin | Hozé, Chris | Costes, Valentin | Boussaha, Mekki | Chaulot-Talmon, Aurélie | Ali, Francesca | Boichard, Didier | Kiefer, Hélène | Sanchez, Marie-Pierre

Edité par CCSD ; Wageningen Academic Publishers -

Session 69. Epigenetics, adaptation and intergenerational transmission. International audience. Methylation quantitative trait loci (meQTL) are genetic variants that influence DNA methylation. In cattle, littleis 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 obtainedby reduced representation bisulfite sequencing. After filtering out CpGs without individual variability or co-localizingwith SNPs, we performed sequence-based GWAS of three groups of methylation phenotypes: (1) principalcomponent 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 examinedthe SNPs significantly associated with CpG methylation (-log10(P) > 7.3) and classified them according to theirproximity to the CpG, i.e. cis (<1 Mb), cis long-range (>1Mb, on the same chromosome), and trans (on differentchromosomes). We found meQTLs for all phenotypic categories, most of which had cis-regulatory effects. Inaddition, our study identified candidate genes involved in methylation pathways. Taken together, these resultsdemonstrate a genetic determinism of DNA methylation in cattle and thus an interplay between genetic variationand epigenetic regulation. CF is recipient of a CIFRE PhD grant from ANRT and APIS-GENE. This work waspart of the POLYPHEME project funded by ANR (ANR-21-CE20-0021) and APIS-GENE.

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