|FANG, LINGZHAO - University Of Maryland|
|JIANG, JICAI - University Of Maryland|
|LI, BINGJIE - Oak Ridge Institute For Science And Education (ORISE)|
|ZHOU, YANG - Huazhong Agricultural University|
|FREEBERN, ELLEN - University Of Maryland|
|Liu, Ge - George|
|MA, LI - University Of Maryland|
Submitted to: Communications Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/6/2019
Publication Date: 3/14/2019
Citation: Fang, L., Jiang, J., Li, B., Zhou, Y., Freebern, E., Van Raden, P.M., Cole, J.B., Liu, G., Ma, L. 2019. Genetic and epigenetic architecture of paternal origin contribute to gestation length in cattle. Communications Biology. 2:100. https://doi.org/10.1038/s42003-019-0341-6.
Interpretive Summary: Gestation period is a crucial time period in mammalian development. A better understanding of the genetic variants that affect gestation length is very important for human health and livestock performance. We analyzed gestation length for 27,214 Holstein bulls using imputed sequence variants (~ 3 million). We identified 25 candidate genes for gestation length, revealed that the paternal genome contributes to gestation length mainly by regulating embryonic development, and validated the results using sperm DNA methylation data. Our findings provided new insights into gestation length in cattle, which may also provide valuable knowledge for other mammals, including human.
Technical Abstract: Gestation period is a crucial time point in mammalian development, which highly associates with human health and livestock performance. Both maternal and fetal genomes can directly contribute to gestation length (GL). Yet, few studies have investigated the indirect contributions of the paternal genome and epigenome to GL. Here we studied the paternal genetic and epigenetic impacts on GL in cattle by analyzing imputed sequence variants (~ 3 million) of 27,214 bulls and sperm methylomes with extreme phenotypes. Our genome-wide association study (GWAS) and fine-mapping analyses revealed 25 paternal candidate genes (e.g., HSF1 and MYH10) for GL. GWAS signal enrichment analyses demonstrated that many pathways related to embryonic development were involved in GL. By integrating GWAS with sperm methyomes, we found that GWAS signals were significantly (P < 0.05) enriched in differentially methylated regions in sperm that were associated with high and low GL. We also showed that GL shared the underlying epigenetic architecture in sperm with other genetically correlated traits, such as calving ability, stature, and conception rates. Furthermore, we provided the genome, epigenome, transcriptome, and selection evidence implicating the ZNF613 gene as the candidate gene for GL and many other dairy traits of economic importance. Our findings support that the paternal genome and epigenome impact GL through regulation of embryonic development, and provide molecular mechanisms underlying the associations of GL with other dairy traits (e.g., fertility and conformation), as well as suggest that epigenetic alterations and selection may help to shape the genetic architecture of complex traits.