Abstract
The length of gestation can affect offspring health and performance. Both maternal and fetal effects contribute to gestation length; however, paternal contributions to gestation length remain elusive. Using genome-wide association study (GWAS) in 27,214 Holstein bulls with millions of gestation records, here we identify nine paternal genomic loci associated with cattle gestation length. We demonstrate that these GWAS signals are enriched in pathways relevant to embryonic development, and in differentially methylated regions between sperm samples with long and short gestation length. We reveal that gestation length shares genetic and epigenetic architecture in sperm with calving ability, body depth, and conception rate. While several candidate genes are detected in our fine-mapping analysis, we provide evidence indicating ZNF613 as a promising candidate for cattle gestation length. Collectively, our findings support that the paternal genome and epigenome can impact gestation length potentially through regulation of the embryonic development.
Highlights
The length of gestation can affect offspring health and performance
Our single-marker genome-wide association study (GWAS) revealed nine quantitative trait loci (QTL) that were located in the Bos taurus chromosome (BTA) 4, 5, 7, 10, 14, 18, 19, and 28, respectively (Fig. 1a)
Our following fine-mapping analyses on these nine QTL regions determined 25 candidate genes for gestation length, including multiple genes participating in the embryonic development (e.g., HSF122, MYH1023,24, NDEL125, and NRG226), immune responses (e.g., HCFC2, and CYSTM1), DNA processing (e.g., WWP2, CDKL1, ZNF613, and CPSF1), and cell differentiation (e.g., ZNF16 and ARID4B) (Fig. 1a; Supplementary Data 1)
Summary
The length of gestation can affect offspring health and performance. Both maternal and fetal effects contribute to gestation length; paternal contributions to gestation length remain elusive. Based on millions of mating and dairy production records, the U.S dairy cattle database has archived a large amount of reliable phenotypes on gestation length for thousands of service bulls. This data resource provides valuable information to study the paternal impacts on gestation length in mammals. We characterized genome-wide DNA methylation alterations in sperm that were associated with gestation length and three genetically correlated traits of economic importance, sire calving ease (SCE), body depth (BDE), and cow conception rate (CCR), by comparing sperm methylomes of 18 representative animals with extreme phenotypes[19]. We believe that our findings in cattle can provide valuable knowledge for other mammals, including human and rodents
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