Analyses of inter-individual variations in sperm DNA methylation reveal their regulatory role in gene expression and association with reproduction traits in cattle

Authors: LIU, SHULI - China Agricultural University; FANG, LINZHAO - University Of Edinburgh; ZHOU, YANG - Huazhong Agricultural University; SANTOS, DANIEL - University Of Maryland; XIANG, RUIDONG - University Of Melbourne; DAETWYLER, HAS - La Trobe University; CHAMBERLAIN, AMANDA - Agriculture Victoria; Cole, John; Li, Congjun - Cj; YU, YING - China Agricultural University; MA, LI - University Of Maryland; ZHANG, SHENGLI - China Agricultural University; Liu, Ge - George

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/28/2019
Publication Date: 11/21/2019
Citation: Liu, S., Fang, L., Zhou, Y., Santos, D.J.A., Xiang, R., Daetwyler, H.D., Chamberlain, A.J., Cole, J.B., Li, C., Yu, Y., Ma, L., Zhang, S., Liu, G. 2019. Analyses of inter-individual variations in sperm DNA methylation reveal their regulatory role in gene expression and association with reproduction traits in cattle. BMC Genomics. 20:888. https://doi.org/10.1186/s12864-019-6228-6.
DOI: https://doi.org/10.1186/s12864-019-6228-6

Interpretive Summary: DNA methylation plays important roles in many processes like gene expression, genomic imprinting, repression of transposable elements, and gametogenesis. We detected sperm DNA methylation variations among individual bulls and found their associations with reproduction traits, highlighting the potential of using DNA methylation information in genomic improvement programs for cattle. Farmers, scientist, and policy planners who need improve animal health and production based on genome-enable animal selection will benefit from this study.

Technical Abstract: We characterized sperm DNA methylation variations among individual bulls and investigated their associations with complex traits. Based on the correlation patterns of methylation levels of neighboring CpG sites among 28 sperm whole genome bisulfite sequencing (WGBS) data (486 x coverage), we obtained 31,272 methylation haplotype blocks (MHBs). Among them, we defined conserved methylated regions (CMRs), variably methylated regions (VMRs) and highly variably methylated regions (HVMRs) among individuals, and showed that HVMRs might play roles in transcriptional regulation and function in complex traits variation and adaptive evolution by integrating evidence from traditional and molecular quantitative trait loci (QTL), and selection signatures. Using a weighted correlation network analysis (WGCNA), we also detected a co-regulated module of HVMRs that was significantly associated with reproduction traits, and enriched for glycosyltransferase genes, which play critical roles in spermatogenesis and fertilization. In addition, we identified 46 VMRs significantly associated with reproduction traits, nine of which were regulated by cis-SNPs, implying the possible intrinsic relationships among genomic variations, DNA methylation, and phenotypes. These significant VMRs were co-localized (+- 10kb) with genes related to sperm motility and reproduction, including ZFP36L1, CRISP2 and HGF. We provided further evidence that rs109326022 within a predominant QTL on BTA18 might influence the reproduction traits through regulating the methylation level of nearby genes JOSD2 and ASPDH in sperm. In summary, our results demonstrated associations of sperm DNA methylation with reproduction traits, highlighting the potential of using DNA methylation information in genomic improvement programs for cattle.