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Highly efficient generation of sheep with a defined FecBB mutation via adenine base editing.
Genet Sel Evol. 2020 Jul 01; 52(1):35.GS

Abstract

Base editing has the potential to improve important economic traits in agriculture and can precisely convert single nucleotides in DNA or RNA sequences into minimal double-strand DNA breaks (DSB). Adenine base editors (ABE) have recently emerged as a base editing tool for the conversion of targeted A:T to G:C, but have not yet been used in sheep. ABEmax is one of the latest versions of ABE, which consists of a catalytically-impaired nuclease and a laboratory-evolved DNA-adenosine deaminase. The Booroola fecundity (FecBB) mutation (g.A746G, p.Q249R) in the bone morphogenetic protein receptor 1B (BMPR1B) gene influences fecundity in many sheep breeds. In this study, by using ABEmax we successfully obtained lambs with defined point mutations that result in an amino acid substitution (p.Gln249Arg). The efficiency of the defined point mutations was 75% in newborn lambs, since six lambs were heterozygous at the FecBB mutation site (g.A746G, p.Q249R), and two lambs were wild-type. We did not detect off-target mutations in the eight edited lambs. Here, we report the validation of the first gene-edited sheep generated by ABE and highlight its potential to improve economically important traits in livestock.

Authors+Show Affiliations

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.College of Veterinary Medicine, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.College of Biotechnology, Guilin Medical University, Guilin, China.Ningxia Tianyuan Tan Sheep Farm, Hongsibu, China.Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt, Germany.School of Life Science and Technology, ShanghaiTech University, Shanghai, China.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China. xiaolongwang@nwafu.edu.cn.College of Veterinary Medicine, Northwest A&F University, Yangling, China. mabh@nwafu.edu.cn.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China. chenyulin@nwafu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32611306

Citation

Zhou, Shiwei, et al. "Highly Efficient Generation of Sheep With a Defined FecBB Mutation Via Adenine Base Editing." Genetics, Selection, Evolution : GSE, vol. 52, no. 1, 2020, p. 35.
Zhou S, Ding Y, Liu J, et al. Highly efficient generation of sheep with a defined FecBB mutation via adenine base editing. Genet Sel Evol. 2020;52(1):35.
Zhou, S., Ding, Y., Liu, J., Liu, Y., Zhao, X., Li, G., Zhang, C., Li, C., Wang, Y., Kalds, P., Gao, Y., Zong, B., Huang, X., Huang, S., Yu, H., Kou, Q., Petersen, B., Huang, X., Wang, X., ... Chen, Y. (2020). Highly efficient generation of sheep with a defined FecBB mutation via adenine base editing. Genetics, Selection, Evolution : GSE, 52(1), 35. https://doi.org/10.1186/s12711-020-00554-6
Zhou S, et al. Highly Efficient Generation of Sheep With a Defined FecBB Mutation Via Adenine Base Editing. Genet Sel Evol. 2020 Jul 1;52(1):35. PubMed PMID: 32611306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Highly efficient generation of sheep with a defined FecBB mutation via adenine base editing. AU - Zhou,Shiwei, AU - Ding,Yige, AU - Liu,Jiao, AU - Liu,Yao, AU - Zhao,Xiaoe, AU - Li,Guanwei, AU - Zhang,Chenguang, AU - Li,Chao, AU - Wang,Ying, AU - Kalds,Peter, AU - Gao,Yawei, AU - Zong,Bo, AU - Huang,Xiaoyu, AU - Huang,Shuhong, AU - Yu,Honghao, AU - Kou,Qifang, AU - Petersen,Bjoern, AU - Huang,Xingxu, AU - Wang,Xiaolong, AU - Ma,Baohua, AU - Chen,Yulin, Y1 - 2020/07/01/ PY - 2020/02/14/received PY - 2020/06/18/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline SP - 35 EP - 35 JF - Genetics, selection, evolution : GSE JO - Genet. Sel. Evol. VL - 52 IS - 1 N2 - Base editing has the potential to improve important economic traits in agriculture and can precisely convert single nucleotides in DNA or RNA sequences into minimal double-strand DNA breaks (DSB). Adenine base editors (ABE) have recently emerged as a base editing tool for the conversion of targeted A:T to G:C, but have not yet been used in sheep. ABEmax is one of the latest versions of ABE, which consists of a catalytically-impaired nuclease and a laboratory-evolved DNA-adenosine deaminase. The Booroola fecundity (FecBB) mutation (g.A746G, p.Q249R) in the bone morphogenetic protein receptor 1B (BMPR1B) gene influences fecundity in many sheep breeds. In this study, by using ABEmax we successfully obtained lambs with defined point mutations that result in an amino acid substitution (p.Gln249Arg). The efficiency of the defined point mutations was 75% in newborn lambs, since six lambs were heterozygous at the FecBB mutation site (g.A746G, p.Q249R), and two lambs were wild-type. We did not detect off-target mutations in the eight edited lambs. Here, we report the validation of the first gene-edited sheep generated by ABE and highlight its potential to improve economically important traits in livestock. SN - 1297-9686 UR - https://www.unboundmedicine.com/medline/citation/32611306/Highly_efficient_generation_of_sheep_with_a_defined_FecBB_mutation_via_adenine_base_editing L2 - https://gsejournal.biomedcentral.com/articles/10.1186/s12711-020-00554-6 DB - PRIME DP - Unbound Medicine ER -
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