Livestock breeding for the 21st century: the promise of the editing revolution

Abstract

In recent years there has been a veritable explosion in the use of genome editors to create site-specific changes, both in vitro and in vivo, to the genomes of a multitude of species for both basic research and biotechnology. Livestock, which form a vital component of most societies, are no exception. While selective breeding has been hugely successful at enhancing some production traits, the rate of progress is often slow and is limited to variants that exist within the breeding population. Genome editing provides the potential to move traits between breeds, in a single generation, with no impact on existing productivity or to develop de novo phenotypes that tackle intractable issues such as disease. As such, genome editors provide huge potential for ongoing livestock development programs in light of increased demand and disease challenge. This review will highlight some of the more notable agricultural applications of this technology in livestock.

Keywords

cattle / pig / sheep / chicken / aquaculture / CRISPR

References

[1] Torres-Perez R, Garcia-Martin J A, Montoliu L, Oliveros J C, Pazos F. WeReview: CRISPR tools—live repository of computational tools for assisting CRISPR/Cas experiments. Bioengineering, 2019, 6(3): 63

[2] Chaudhary K, Chattopadhyay A, Pratap D. The evolution of CRISPR/Cas9 and their cousins: hope or hype? Biotechnology Letters, 2018, 40(3): 465–477

[3] Pickar-Oliver A, Gersbach C A. The next generation of CRISPR-Cas technologies and applications. Nature Reviews: Molecular Cell Biology, 2019, 20(8): 490–507

[4] Christian M, Cermak T, Doyle E L, Schmidt C, Zhang F, Hummel A, Bogdanove A J, Voytas D F. Targeting DNA double-strand breaks with TAL effector nucleases. Genetics, 2010, 186(2): 757–761

[5] Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna J A, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 2012, 337(6096): 816–821

[6] Cong L, Ran F A, Cox D, Lin S, Barretto R, Habib N, Hsu P D, Wu X, Jiang W, Marraffini L A, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science, 2013, 339(6121): 819–823

[7] Mali P, Yang L, Esvelt K M, Aach J, Guell M, DiCarlo J E, Norville J E, Church G M. RNA-guided human genome engineering via Cas9. Science, 2013, 339(6121): 823–826

[8] Hauschild J, Petersen B, Santiago Y, Queisser A L, Carnwath J W, Lucas-Hahn A, Zhang L, Meng X, Gregory P D, Schwinzer R, Cost G J, Niemann H. Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(29): 12013–12017

[9] Lillico S G, Proudfoot C, Carlson D F, Stverakova D, Neil C, Blain C, King T J, Ritchie W A, Tan W, Mileham A J, McLaren D G, Fahrenkrug S C, Whitelaw C B. Live pigs produced from genome edited zygotes. Scientific Reports, 2013, 3(1): 2847

[10] Park K E, Kaucher A V, Powell A, Waqas M S, Sandmaier S E, Oatley M J, Park C H, Tibary A, Donovan D M, Blomberg L A, Lillico S G, Whitelaw C B, Mileham A, Telugu B P, Oatley J M. Generation of germline ablated male pigs by CRISPR/Cas9 editing of the NANOS2 gene. Scientific Reports, 2017, 7(1): 40176

[11] He Z, Zhang T, Jiang L, Zhou M, Wu D, Mei J, Cheng Y. Use of CRISPR/Cas9 technology efficiently targetted goat myostatin through zygotes microinjection resulting in double-muscled phenotype in goats. Bioscience Reports, 2018, 38(6): BSR20180742

[12] Sheets T P, Park C H, Park K E, Powell A, Donovan D M, Telugu B P. Somatic cell nuclear transfer followed by CRIPSR/Cas9 microinjection results in highly efficient genome editing in cloned pigs. International Journal of Molecular Sciences, 2016, 17(12): 2031

[13] Carlson D F, Lancto C A, Zang B, Kim E S, Walton M, Oldeschulte D, Seabury C, Sonstegard T S, Fahrenkrug S C. Production of hornless dairy cattle from genome-edited cell lines. Nature Biotechnology, 2016, 34(5): 479–481

[14] Zhou S, Yu H, Zhao X, Cai B, Ding Q, Huang Y, Li Y, Li Y, Niu Y, Lei A, Kou Q, Huang X, Petersen B, Ma B, Chen Y, Wang X. Generation of gene-edited sheep with a defined Booroola fecundity gene (FecB^B) mutation in bone morphogenetic protein receptor type 1B (BMPR1B) via clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9. Reproduction, Fertility, and Development, 2018, 30(12): 1616–1621

[15] Lillico S G, Proudfoot C, King T J, Tan W, Zhang L, Mardjuki R, Paschon D E, Rebar E J, Urnov F D, Mileham A J, McLaren D G, Whitelaw C B. Mammalian interspecies substitution of immune modulatory alleles by genome editing. Scientific Reports, 2016, 6(1): 21645

[16] Tan W, Carlson D F, Lancto C A, Garbe J R, Webster D A, Hackett P B, Fahrenkrug S C. Efficient nonmeiotic allele introgression in livestock using custom endonucleases. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(41): 16526–16531

[17] Young A E, Mansour T A, McNabb B R, Owen J R, Trott J F, Brown C T, van Eenennaam A L. Genomic and phenotypic analyses of six offspring of a genome-edited hornless bull. Nature Biotechnology, 2019 [Published Online] doi: 10.1038/s41587-019-0266-0

[18] Grobet L, Royo Martin L J, Poncelet D, Pirottin D, Brouwers B, Riquet J, Schoeberlein A, Dunner S, Ménissier F, Massabanda J, Fries R, Hanset R, Georges M. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature Genetics, 1997, 17(1): 71–74

[19] Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibé B, Bouix J, Caiment F, Elsen J M, Eychenne F, Larzul C, Laville E, Meish F, Milenkovic D, Tobin J, Charlier C, Georges M. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nature Genetics, 2006, 38(7): 813–818

[20] Proudfoot C, Carlson D F, Huddart R, Long C R, Pryor J H, King T J, Lillico S G, Mileham A J, McLaren D G, Whitelaw C B A, Fahrenkrug S C. Genome edited sheep and cattle. Transgenic Research, 2015, 24(1): 147–153

[21] Crispo M, Mulet A P, Tesson L, Barrera N, Cuadro F, dos Santos-Neto P C, Nguyen T H, Crénéguy A, Brusselle L, Anegón I, Menchaca A. Efficient generation of myostatin knock-out sheep using CRISPR/Cas9 technology and microinjection into zygotes. PLoS One, 2015, 10(8): e0136690

[22] Wang K, Ouyang H, Xie Z, Yao C, Guo N, Li M, Jiao H, Pang D. Efficient generation of myostatin mutations in pigs using the CRISPR/Cas9 system. Scientific Reports, 2015, 5(1): 16623

[23] Davis G H. Fecundity genes in sheep. Animal Reproduction Science, 2004, 82–83: 247–253

[24] Yue C, Bai W L, Zheng Y Y, Hui T Y, Sun J M, Guo D, Guo S L, Wang Z Y. Correlation analysis of candidate gene SNP for high-yield in Liaoning cashmere goats with litter size and cashmere performance. Animal Biotechnology, 2019 [Published Online] doi: 10.1080/10495398.2019.1652188

[25] Wei J, Wagner S, Maclean P, Brophy B, Cole S, Smolenski G, Carlson D F, Fahrenkrug S C, Wells D N, Laible G. Cattle with a precise, zygote-mediated deletion safely eliminate the major milk allergen β-lactoglobulin. Scientific Reports, 2018, 8(1): 7661

[26] Cui C, Song Y, Liu J, Ge H, Li Q, Huang H, Hu L, Zhu H, Jin Y, Zhang Y. Gene targeting by TALEN-induced homologous recombination in goats directs production of β-lactoglobulin-free, high-human lactoferrin milk. Scientific Reports, 2015, 5(1): 10482

[27] Zhou W, Wan Y, Guo R, Deng M, Deng K, Wang Z, Zhang Y, Wang F. Generation of β-lactoglobulin knock-out goats using CRISPR/Cas9. PLoS One, 2017, 12(10): e0186056

[28] Nan Y, Wu C, Gu G, Sun W, Zhang Y J, Zhou E M. Improved vaccine against PRRSV: current progress and future perspective. Frontiers in Microbiology, 2017, 8: 1635

[29] Calvert J G, Slade D E, Shields S L, Jolie R, Mannan R M, Ankenbauer R G, Welch S K. CD163 expression confers susceptibility to porcine reproductive and respiratory syndrome viruses. Journal of Virology, 2007, 81(14): 7371–7379

[30] Whitworth K M, Rowland R R, Ewen C L, Trible B R, Kerrigan M A, Cino-Ozuna A G, Samuel M S, Lightner J E, McLaren D G, Mileham A J, Wells K D, Prather R S. Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nature Biotechnology, 2016, 34(1): 20–22

[31] Burkard C, Opriessnig T, Mileham A J, Stadejek T, Ait-Ali T, Lillico S G, Whitelaw C B A, Archibald A L. Pigs lacking the scavenger receptor cysteine-rich domain 5 of CD163 are resistant to porcine reproductive and respiratory syndrome virus 1 infection. Journal of Virology, 2018, 92(16): e0045-18

[32] Delmas B, Gelfi J, L’Haridon R, Vogel L K, Sjöström H, Norén O, Laude H. Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature, 1992, 357(6377): 417–420

[33] Yeager C L, Ashmun R A, Williams R K, Cardellichio C B, Shapiro L H, Look A T, Holmes K V. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature, 1992, 357(6377): 420–422

[34] Whitworth K M, Rowland R R R, Petrovan V, Sheahan M, Cino-Ozuna A G, Fang Y, Hesse R, Mileham A, Samuel M S, Wells K D, Prather R S. Resistance to coronavirus infection in amino peptidase N-deficient pigs. Transgenic Research, 2019, 28(1): 21–32

[35] Oh J S, Song D S, Park B K. Identification of a putative cellular receptor 150 kDa polypeptide for porcine epidemic diarrhea virus in porcine enterocytes. Journal of Veterinary Science, 2003, 4(3): 269–275

[36] Kamau A N, Park J E, Park E S, Yu J E, Rho J, Shin H J. Porcine amino peptidase N domain VII has critical role in binding and entry of porcine epidemic diarrhea virus. Virus Research, 2017, 227: 150–157

[37] Shirato K, Maejima M, Islam M T, Miyazaki A, Kawase M, Matsuyama S, Taguchi F. Porcine aminopeptidase N is not a cellular receptor of porcine epidemic diarrhea virus, but promotes its infectivity via aminopeptidase activity. Journal of General Virology, 2016, 97(10): 2528–2539

[38] Li W, Luo R, He Q, van Kuppeveld F J M, Rottier P J M, Bosch B J. Aminopeptidase N is not required for porcine epidemic diarrhea virus cell entry. Virus Research, 2017, 235: 6–13

[39] Gratacap R L, Wargelius A, Edvardsen R B, Houston R D. Potential of genome editing to improve aquaculture breeding and production. Trends in Genetics, 2019, 35(9): 672–684

[40] Li M, Yang H, Zhao J, Fang L, Shi H, Li M, Sun Y, Zhang X, Jiang D, Zhou L, Wang D. Efficient and heritable gene targeting in tilapia by CRISPR/Cas9. Genetics, 2014, 197(2): 591–599

[41] Santos Nassif Lacerda S M, Costa G M J, da Silva M A, Almeida Campos-Junior P H, Segatelli T M, Peixoto M T D, Resende R R, de França L R. Phenotypic characterization and in vitro propagation and transplantation of the Nile tilapia (Oreochromis niloticus) spermatogonial stem cells. General and Comparative Endocrinology, 2013, 192: 95–106

[42] Khalil K, Elayat M, Khalifa E, Daghash S, Elaswad A, Miller M, Abdelrahman H, Ye Z, Odin R, Drescher D, Vo K, Gosh K, Bugg W, Robinson D, Dunham R. Generation of myostatin gene-edited channel catfish (Ictalurus punctatus) via zygote injection of CRISPR/Cas9 system. Scientific Reports, 2017, 7(1): 7301

[43] Zhong Z, Niu P, Wang M, Huang G, Xu S, Sun Y, Xu X, Hou Y, Sun X, Yan Y, Wang H. Targeted disruption of sp7 and myostatin with CRISPR-Cas9 results in severe bone defects and more muscular cells in common carp. Scientific Reports, 2016, 6(1): 22953

[44] Wang C, Chen Y L, Bian W P, Xie S L, Qi G L, Liu L, Strauss P R, Zou J X, Pei D S. Deletion of MSTNa and MSTNb impairs the immune system and affects growth performance in zebrafish. Fish & Shellfish Immunology, 2018, 72: 572–580

[45] Wargelius A, Leininger S, Skaftnesmo K O, Kleppe L, Andersson E, Taranger G L, Schulz R W, Edvardsen R B. Dnd knockout ablates germ cells and demonstrates germ cell independent sex differentiation in Atlantic salmon. Scientific Reports, 2016, 6(1): 21284

[46] Zhang J, Song F, Sun Y, Yu K, Xiang J. CRISPR/Cas9-mediated deletion of EcMIH shortens metamorphosis time from mysis larva to postlarva of Exopalaemon carinicauda. Fish & Shellfish Immunology, 2018, 77: 244–251

[47] Yu H, Li H, Li Q, Xu R, Yue C, Du S. Targeted gene disruption in pacific oyster based on CRISPR/Cas9 ribonucleoprotein complexes. Marine Biotechnology, 2019, 21(3): 301–309

[48] van de Lavoir M C, Diamond J H, Leighton P A, Mather-Love C, Heyer B S, Bradshaw R, Kerchner A, Hooi L T, Gessaro T M, Swanberg S E, Delany M E, Etches R J. Germline transmission of genetically modified primordial germ cells. Nature, 2006, 441(7094): 766–769

[49] Taylor L, Carlson D F, Nandi S, Sherman A, Fahrenkrug S C, McGrew M J. Efficient TALEN-mediated gene targeting of chicken primordial germ cells. Development, 2017, 144(5): 928–934

[50] Woodcock M E, Gheyas A A, Mason A S, Nandi S, Taylor L, Sherman A, Smith J, Burt D W, Hawken R, McGrew M J. Reviving rare chicken breeds using genetically engineered sterility in surrogate host birds. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(42): 20930–20937

[51] Jenko J, Gorjanc G, Cleveland M A, Varshney R K, Whitelaw C B A, Woolliams J A, Hickey J M. Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs. Genetics, Selection, Evolution, 2015, 47(1): 55

[52] Eriksson S, Jonas E, Rydhmer L, Röcklinsberg H. Invited review: breeding and ethical perspectives on genetically modified and genome edited cattle. Journal of Dairy Science, 2018, 101(1): 1–17

[53] McConnachie E, Hötzel M J, Robbins J A, Shriver A, Weary D M, von Keyserlingk M A G. Public attitudes towards genetically modified polled cattle. PLoS One, 2019, 14(5): e0216542

[54] Yunes M C, Teixeira D L, von Keyserlingk M A G, Hötzel M J. Is gene editing an acceptable alternative to castration in pigs? PLoS One, 2019, 14(6): e0218176

[55] McPhetres J, Rutjens B T, Weinstein N, Brisson J A. Modifying attitudes about modified foods: increased knowledge leads to more positive attitudes. Journal of Environmental Psychology, 2019, 64: 21–29

Compliance with ethics guidelines

Chris Proudfoot, Gus McFarlane, Bruce Whitelaw, and Simon Lillico declare that they have no conflicts of interest or financial conflicts to disclose.

This article does not contain any studies with human or animal subjects performed by any of the authors.

RIGHTS & PERMISSIONS

The Author(s) 2019. Published by Higher Education Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)