|FANG, LINGZHAO - University Of Maryland|
|ZHOU, YANG - Huazhong Agricultural University|
|LIU, SHULI - China Agricultural University|
|JIANG, JICAI - University Of Maryland|
|LI, BINGJIE - Oak Ridge Institute For Science And Education (ORISE)|
|Schroeder, Steven - Steve|
|Rosen, Benjamin - Ben|
|Van Tassell, Curtis - Curt|
|MA, LI - University Of Maryland|
|Liu, Ge - George|
Submitted to: Epigenomes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/11/2019
Publication Date: 5/16/2019
Citation: Fang, L., Zhou, Y., Liu, S., Jiang, J., Bickhart, D.M., Null, D.J., Li, B., Schroeder, S.G., Rosen, B.D., Cole, J.B., Van Tassell, C.P., Ma, L., Liu, G. 2019. Integrating signals from sperm methylome analysis and genome-wide association study for a better understanding of male fertility in cattle. Epigenomes. 3(2):10. https://doi.org/10.3390/epigenomes3020010.
Interpretive Summary: DNA methylation plays important roles in many processes like gene expression, genomic imprinting, repression of transposable elements, and gametogenesis. We detected genomic regions (including 16 genes as candidate biomarkers), that experienced DNA methylation alterations in sperm, were associated with aging and male fertility in cattle. This study also demonstrated that functional annotations can help to explain GWAS results for complex traits and diseases. 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: Background: Decreased male fertility is a big concern in both human society and livestock industry. The sperm DNA methylation is commonly believed to be associated with the male fertility. However, due to the lack of accurate male fertility records (i.e., limited mating times), few studies have investigated the comprehensive impacts of sperm DNA methylation on male fertility in mammals. Results: Here, we investigated the relationships between sperm DNA methylation and male fertility in cattle by integrating large-scale (n = 27,214) genome-wide association studies (GWAS) of 35 complex traits (including 12 male fertility traits) and sperm DNA methylation. We detected genomic regions that experienced DNA methylation alterations in sperm that were associated with aging and extreme fertility phenotypes (e.g., sire-conception rate, SCR). We found genes (e.g., HOX gene clusters and microRNAs) located in dynamic hypomethylated regions (HMRs) and partially methylated domains (PMDs) were significantly involved in the embryonic development. We demonstrated that genomic regions gained methylation rather than those lost methylation during aging and in animals with low-SCR were significantly and selectively enriched for GWAS signals of male fertility traits. Our study detected 16 genes as the most promising candidate genes for male fertility, including SAMD5 and PDE5A. Conclusions: Our current study illustrated the important contribution of sperm DNA methylation to the genetic architecture underlying male fertility in cattle and demonstrated the usefulness of functional annotations in enhancing the biological interpretation of GWAS results for complex traits and diseases.