Genome-wide recombination map construction from single sperm sequencing in cattle

Authors: YANG, LIU - Sichuan Agricultural University; GAO, YAHUI - University Of Maryland; LI, MINGXUN - Yangzhou University; PARK, KI-EUN - University Of Maryland; LIU, SHULI - China Agricultural University; KANG, XIAOLONG - Lanzhou University; LIU, MEI - Hunan Agricultural University; OSWALT, ADAM - Select Sires, Inc; FANG, LINGZHAO - University Of Edinburgh; TELUGU, BHANU - University Of Maryland; SATTLER, CHARLES - Select Sires, Inc; Cole, John; SEROUSSI, EYAL - Volcani Center (ARO); XU, LINGYANG - Chinese Agricultural University; Li, Congjun - Cj; LI, LI - Sichuan Agricultural University; ZHANG, HONGPING - Sichuan Agricultural University; Rosen, Benjamin - Ben; Van Tassell, Curtis - Curt; MA, LI - University Of Maryland; Liu, Ge - George

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/29/2021
Publication Date: 5/3/2022
Citation: Yang, L., Gao, Y., Li, M., Park, K., Liu, S., Kang, X., Liu, M., Oswalt, A., Fang, L., Telugu, B.P., Sattler, C.G., Cole, J.B., Seroussi, E., Xu, L., Li, C., Li, L., Zhang, H., Rosen, B.D., Van Tassell, C.P., Ma, L., Liu, G. 2022. Genome-wide recombination map construction from single sperm sequencing in cattle. BMC Genomics. 23(1):181. https://doi.org/10.1186/s12864-022-08415-w.
DOI: https://doi.org/10.1186/s12864-022-08415-w

Interpretive Summary: Comprehensive analyses of tissues at single-cell level will benefit our understanding of genetic bases for complex traits. We provided the first single-cell analysis of recombination, de novo mutation and genome instability in bovine sperm. These results fill our knowledge gaps and provide the foundation for incorporating new knowledge into the future animal breeding program. Farmers, scientist, and policy planners who need improve animal health and production based on genome-enabled animal selection will benefit from this study.

Technical Abstract: Background: Meiotic recombination, de novo mutation, genome instability like structural variation (SV), large copy number variation (CNV) and/or aneuploidy are important phenomena contributing to gamete genome diversity. However, except for human and a few model organisms, they are not well studied in other mammals including cattle. Results: To investigate how the cattle genome is impacted by these processes, we sequenced 143 single sperms from two Holstein bulls, phased their genomes. ; and mapped recombination events at high resolution. In the absence of evolutionary selection pressure in fertilization and survival, recombination in sperm is enriched near distal chromosomal ends and noncoding regions, revealing that such a pattern is intrinsic to the molecular mechanism of meiosis. From single sperms with uniform sequencing coverage, we observed a similar distal chromosomal distribution for genome instability (SV, CNV and/or aneuploidy) on a global per-sperm basis. Using deep sequencing of ten single sperms, we found that de novo mutations were similarly but unevenly distributed across the individual sperm chromosomes with a rate ranging from 2.05e-08 to 7.63e-08. Furthermore, we were able to validate these findings in single sperms by comparing them with results derived from sequencing a family of trio diploid genomes and our previous studies of recombination in cattle pedigree. Conclusion: We reported patterns of distal chromosomal distributions for recombination, de novo mutation, SV, and large CNV in bovine sperms. To our knowledge, this is the first large-scale single sperm cell sequencing effort in livestock, which provides useful information for future studies of recombination, genome instability, and male infertility.