Practical value of genomics for the larger livestock industry in South Africa

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1 UNIVERSITY OF PRETORIA Practical value of genomics for the larger livestock industry in South Africa Esté van Marle-Köster (PhD Pr. Anim. Sci) Department of Animal & Wildlife Sciences Faculty of Natural and Agricultural Sciences 1

2 It seems to me that the natural world is the greatest source of excitement; The greatest source of visual beauty; The greatest source of intellectual interest It is the greatest source of so much life that makes life worth living Sir David Attenborough If I may be so bold For today replace the natural world with world of genetics /livestock

3 Focus for today s talk.. Introduction Molecular genetics applied to livestock Practical value of the research For livestock breeders - focus on SA livestock breeders Genomic selection for SA livestock breeders Prerequisites for successful implementation Different species different goals Potential strengths & cost implications Can SA breeders survive without genomics Concluding remarks

4 Introduction: molecular genetics applied to livestock Almost 2 decades of research and development using molecular technology provided us with: DNA marker discovery Genome mapping Studies for QTL Complete genome sequencing Discovery of Single Nucleotide Polymorphisms (SNP) Development of specie-specific chips routine genotyping and available for all livestock species

5 First phase of application of genomic tools Diagnostic tests for defects most useful QTL studies Explained limited variation in traits studied Genestar test 1989 first test for marbling explained < 1% of variation Improved on first test 56 marker test Variation explained in marbling 0-3.6% Tenderness % It was clear that QTL approach will not provide the solutions Technology provided new avenues

6 Summary of Farm animal genomes sequenced Species Genome size ( Gb) Year Chicken (Gallus Gallus) Dog (Canis Familiaris) Sheep (Ovis Aries) Cattle (Bos taurus) Horse (Equus caballus) Pig (Sus Scrofa) Cat (Felis sylvestris) Goat

7 Practical value of these discoveries Identification of Single genes associated with genetic defects Major genes associated with production Commercialization - diagnostic tests

8 Genetic defects Often the result of specific trait selection Strong selection for small stature in Hereford in early 1900 s Mutation for dwarfism Traced with pedigree info to St Louis Lad born in 1899 Selection for superior carcass traits in Angus AM (curly calf) & NH (hydrocephalus) lethal conditions Traced back to Rito9J9 born in 1979 and grandson GAR Precision 1680 born in Sept 1990 Work by Beever (2009) indicated 10% of Angus sires were carriers for NH

9 Genetic defects Danger is in NOT knowing If the defect causes foetal loss extent remains unknown Loss in income via low reproduction, dead calves, slow genetic progress Diagnostic tests are therefore essential Breeders can manage single locus recessive genetic conditions! Cost of the test is minimal in comparison to having lethal alleles in your herd Angus successfully selected against the disorders by testing Van Eenennaam & Drake (2012) refers to one of the greatest success stories in genomics With available SNP technology More defects will be discovered It is worth using these tests!

10 Tests available for SA breeders: for cattle Test available DNA profile (includes parentage) Price R142 3 in 1: DNA + Pompe s + CMS R in 1: DNA + Pompe s + CMS + Myostatin R 540 Cytogenetics: 1/29 translocation (Applicable to Simmentaller, Simbra) R 200 Bulldog/Dexter test/freemartin R 175 Double muscling (Myostatin: nt821; F94L; Q204x) R 410 Trichomoniasis foetus R 70 Polled (Taurus & Indicus) R 450 Other tests: vary between SA laboratories Hair colour, BLAD, Curly calf syndrome & Milk quality, Hypotrichosis (hair loss) in Hereford Available on request

11 Sheep and Goats Test available Price DNA profile (includes parentage) R 140 Other tests: Inverdale (Twinning), Loinmax. Myomax Available on request

12 Horses Test available Price DNA profile (includes parentage) R 140 Polysaccharide storage myopathy R210 Combination (HERDA, GBED, HYPP, OLWS) R1500

13 Game Test available Price DNA profile (includes parentage) R 420 Mitochondrial DNA for origin test (Sable & Roan) R Nuclear (Roan) R Nuclear (Bontebuck & Blesbuck) R 785 Impala (Black gene) R Impala (Black gene) (10 samples and more) R 1 000

14 Examples of major genes/mixed inheritance Livestock species Gene/markers tested Dairy cattle DGAT 1 Casein Beef cattle Sheep Pigs CAST GHR CLPG1 FGFR3 DMP1 ESR MC4R IGF2 CYB5A Trait association Milk fat Milk protein Meat quality Meat production muscle growth, fat accretion, feed efficiency, dressing percentage Skeletal growth and/or abnormalities (SLS) growth rate, limb deformities (Rickets) litter size Feed intake, back fat thickness, growth rate Muscle growth, fat deposition, boar taint Boar taint

15 Genetic characterization. Genetic characterization of livestock resources Provides insight to genetic diversity Inbreeding and effective population size Admixture & breed composition Studies conducted based on microsatellite markers More recently SNP markers A number of studies conducted on SA breeds Local chicken resources SA sheep breeds Nguni & Afrikaner cattle breeds Pig breeds

16 DNA based parentage verification Microsatellite marker panels have been developed ISAG working groups for different species to ensure Standardization and comparison between laboratories Panels of between 12 and 18 markers depending on species and effective population size of breed Should be a routine practise More recent SNP panels for parentage ISAG recommended panel of few 100 SNP s Breeds with reference populations and routine genotyping SNP s will replace microsatellites

17 Research has shown Parentage errors result in: Loss in genetic progress Up to 15% with an error rate of 10-15% Estimated error rates from literature: 10% estimated in UK dairy cattle (Visscher et al. 2002) 15 % error in commercial sheep flocks (Dodds et al. 2007) 25 % in S A Angora goat herds (Friedrich, 2010) % In Boran in Kenya ( Kios et al., 2011) Re-ranking of top sires in SA Angora herds (Garritsson et al., 2015)

18 Uptake of DNA based parentage by SA Breeders DNA confirmed parentage Is not compulsory for SA breeds A number of cattle breeds do spot tests yearly basis Relative small % of breeders use DNA to confirm parentage Mostly breeders with multi sires mating systems that do test Breed example Afrikaner SA Angus SA Bonsmara Hereford Nguni % of animals tested using DNA Recorded Logix system

19 Is it worth testing? in 100 cows you invest Stud breeder costs for animal recording Services Membership fee to Society Registration costs (including registration certificate) Production recording Growth tests for 5 bulls/year RTU Total Paternity tests on 20% of progeny( R145/sample) R/year If you have incorrect parentages Affect EBV s all animals linked in your herd and other herds

20 Genomic selection Genomic selection Due to commercialization of SNP discoveries for routine genotyping Providing breeders with Genomic breeding values Especially useful for traits difficult/costly to measure & sex-limited Increase accuracy of selection Shorten generation interval Can select more accurately on young age

21 SNP chips.. Species Identification Platform Classification Number of SNP s Bovine SNP777K (HD) SNP50K GGP-HD 80K SNP150K GGP- LDv3 BOS1 Ilumina Ilumina Ilumina Ilumina Ilumina Affymetrix Commercial Commercial Commercial Commercial Commercial Commercial Ovine Ovine 50K Ilumina Commercial Caprine Caprine 50K Ilumina Consortium Pig Porcine 60K Ilumina Commercial Chicken 600K Affymetrix Commercial Dog Canine HD WG Ilumina Commercial

22 Genomic selection for SA breeders Prerequisites for successful implementation of GS Theoretical/academic aspects Require a reference population for the breed Require a database with genotypes & phenotypes Some research within the breed Service provider to perform estimations Validation Implementation Practical/other aspects Population numbers/size of the breed Collection of biological samples Collection of additional phenotypes Funding Pay the service provider Genotype more animals Apply GEBV s

23 SA livestock breeders opportunities Livestock species differ with regard to Breeding goals & market opportunities Participation in animal recording actual available records Application of other genomic or reproductive tools Population sizes Available biological samples Genomic selection may not be an option for all species

24 Livestock breeders applying basic genetic tools essential for genetic selection/progress in SA Genetic tool Dairy cattle Beef cattle Sheep & goats Pigs Breeding goals Individual identification Performance recording AI/reproductive biotechnologies Parentage testing Genetic evaluation Genomic selection potential high high medium medium

25 Dairy Cattle Registration Production AYRSHIRE S.A. HOLSTEIN JERSEY

26 Beef Cattle Registration Production

27 Sheep Registration Production DOHNE MERINO DORPER - COMMERCIAL DORPER ILE DE FRANCE MERINO - COMMERCIAL MERINO MEATMASTER S.A. MUTTON MERINO

28 Goats Registration Production BOER GOAT INDIGENOUS VELD GOAT KALAHARI REDS SAVANNA GOAT BRITISH ALPINE SAANEN TOGGENBURG

29 Genotypes & phenotypes: starting point For any breed to use GS it implies Long term investment Need phenotypes recorded on farm Some will come with extra effort and cost (Fertility traits & longevity, RTU, feed efficiency) Collect biological samples Limited effort & little cost Some breeds have been banking hairs at SA laboratories/service providers Genotyping will come at extra cost

30 Breeding goals will determine potential benefits Different species/breeds will have goals/markets interest in different traits only use of some of genetic tools

31 Breeding goals will determine potential benefits Dairy industry Stud and commercial industry: one product: milk yield & quality Excellent genetic linkage via AI world industry Opportunity for genotype sharing Essential to test SA animals Dairy industry is leading in application of genomic tools Beef cattle Different markets: market stud bulls, replacement females Commercial farmers - product driven Stud breeders will invest in genomic tools carry the costs Commercial farmers need to understand the long term benefits

32 Potential strengths Structures for animal recording & genetic evaluation For all livestock species in place Available phenotypes Most species have phenotypes for a number of traits Potential for genotype sharing international level Dairy breeds & beef(hereford, Angus, Charolaise) Sheep breeds (Merino)

33 Investment & return on GS? Early days Not simple calculation Will differ among the livestock species and even breeds Depending on breeding goals & products & markets If we can assume that reference populations & GS strategy for the breeds are in place Breeders will use LD routine SNP Will the info obtained result in? Marketing stud bulls with GEBV s higher price? Marketing commercial bulls higher price?

34 Investment & return on GS? Answer is in the bigger picture Higher selection accuracy, especially of younger animals More effective selection of fertility traits Increasing genetic level and overall efficiency of total herd Long term investment Commitment to use all available genomic tools available Not only GS

35 Status of SA research & funding opportunities Research Genomic task team ( Consortium for bovine underway Ovine has a working group A number of Universities are involved: UP, UFS, US, UFH Research institutions: ARC API & ARC Biotechnology Funding LIMITED for research Genomics are expensive - collaboration is essential Successful implementation will depend on industry participation & uptake

36 Beef genomics program(bgp) Livestock Genomics Task Team - established in 2012 Aim: to drive the process of inclusion of genomic data in breeding decisions Bovine Genomic Program developed almost two years Consists of major role-players in the beef research and improvement Representatives ARC, UP, UFS, US and UFH & Beef Breed Societies Developed a funding proposal & strategy for implementing GS for SA beef cattle Major focus on collection of phenotypic data for Fertility traits Efficiency Carcass evaluation 9-10 year project

37 BGP Based on commitment of breeders Breeders will take responsibility for collection of phenotypes Project genotypes for reference populations will be generated Research conducted to apply existing methodology for GEBV estimations Use the data for GWAS in SA populations Funding available for 3 years TIA will consider the next 3 years based on our progress

38 BGP participation Breed Studbook Breeds Genotypes Feed efficiency Carcass Quality Female fertility Feed efficiency EBV's available Carcass quality EBV's available Female fertility EBV's available Economic Index including difficult Bonsmara (SA & Namibia) 7,114 1,500 1,000 1,500 Yes Yes Yes Yes Yes Yes Yes Beefmaster 5,794 1,500 1,000 1,500 Yes Yes Yes Yes Yes Yes Yes Boran 5,794 1,500 1,000 1,500 Yes Yes Yes Yes Yes Yes Yes Drakensberger 2, No Yes GWAS Yes GWAS Yes Partially Angus 2, No Yes Yes Yes Yes Tuli Sussex Hereford Afrikaner Charolais Dexter Gelbvieh Studbook Breeds 28,028 7,130 4,250 6,370 LRF Breeds Breed Genotypes Number of expected records by Dec 2023 Feed efficiency Carcass Quality Female fertility Feed efficiency EBV's available Carcass quality EBV's available Female fertility EBV's available Brahman (SA & Namibia) 7,204 1,500 1,000 1,500 Yes Yes Yes Yes Yes Yes Yes Simbra 5,785 1,500 1,000 1,500 Yes Yes Yes Yes Yes Yes Yes Simmentaler 5,797 1,500 1,000 1,500 Yes Yes Yes Yes Yes Yes Yes Santa Gertrudis 2, No Yes Yes Yes Yes Limousin 1, Progress through international within Breed co-operation LRF Breeds 22,311 5,435 3,425 5,210 Total participants 50,339 12,565 7,675 11,580 Feed efficiency parameters estimated Carcass quality parameters estimated Female fertility parameters estimated Potential progress through GWAS International within breed co-operation potential to be explored Progress through international within Breed co-operation Progress potentially through correlation with Bonsmara Progress through international within Breed co-operation International within breed co-operation potential to be explored International within breed co-operation potential to be explored Economic Index including difficult

39 In other countries High research investments in GS compared to SA USA had the advantage of available DNA repositories Long term selection projects & experimental herds Huge investments were made 1960 s s Livestock in developing countries Africa, India.. Current project in East Africa: 3500 genotypes done Funded by Bill & Melida Gates foundation World wide investment in livestock research < 20% Much lower compared to crops

40 Other benefits from data generated for GS Data generated from GS can be applied: Parentage testing no need for additional test Genome Wide Association studies Focus on specific trait associations Genes of interest Smaller sub sets of SNP s LD chips Across breed analyses Breed diversity & admixture

41 Population structure BON HFD TUL AAN

42 Can SA breeders survive without Genomics? YES & NO Some genomic tools will become essential tools for certain breeds E.g. have to test for certain defects/use DNA based parentage GS will depend on Breeding goals of the specific breed To remain competitive within country and world wide Livestock breeding should not be about survival, but progress And genomics will be essential part of future progress.

43 Genomics need to meet the new world challenges Focus will not be only on increased production to meet higher demands for milk and meat expected to double in developing countries But, The focus will be on increased efficiency of production In SA as in many other developing countries Natural resources are under pressure, land, water Increase efficiency within existing limitations

44 Genomics need to meet the new world challenges Focus will be on traits such as: Feed conversion efficiency in cattle & sheep both difficult & expensive to measure Fertility large impact on efficiency -More fertile cows/ewes with > longevity Reduced methane emissions need to reduce DMI & maintaining production Disease resistance & heat stress - Animals/breeds adapted to changing environments - global warming Introgression of desirable genes of certain breeds using GS & reproductive biotechnology Quality traits- > level of omega-3 in meat /fatty acid profiles in milk consumer demands According to Hayes et al (2012) technologies including GS, WGS, AI and IVF will be required to ensure the genetic gains in these traits

45 Concluding remarks Genomics cannot replace PHENOTYPES Genomics advantages in Eliminating genetic defects Increasing accuracy of selection using DNA based parentage testing Increasing accuracy of selection using GEBV s for certain traits Genomics is costly But long term investment Genomics provides breeders with a useful additional tool for increasing accuracy of selection

46 Acknowledgements Post graduate students in Animal breeding and genetics laboratory Carina Visser & colleagues of SA Stud book 46