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“Ag” biotechnology: animals

“Ag” biotechnology: animals. Livestock and poultry Aqua-farming Dogs, horses, mice Functional genomics and ‘serendipity’ Beyond sequencing genomes: applications. Molecular biotechnology of “Ag”. Animal husbandry, animal science, stockbreeding

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“Ag” biotechnology: animals

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  1. “Ag” biotechnology: animals • Livestock and poultry • Aqua-farming • Dogs, horses, mice • Functional genomics and ‘serendipity’ • Beyond sequencing genomes: applications

  2. Molecular biotechnology of “Ag” • Animal husbandry, animal science, stockbreeding • “the agricultural practice of breeding and raising livestock” • Universities and colleges programs • Involving nutrition, genetics and reproductive physiology • Diverse: chickens, cows, sheep, pigs, fish, reindeer, guinea pig, horses, dogs • Ethical aspects • “Farming” vs natural pressures and stresses on wild animals • Disease, predation, competition • Removing ‘wild’ traits (domestication), removing undesirable traits • Adding desirable traits • “Industrialized” farming vs “Compassion in World Farming”

  3. Bovine: dairy and beef farming and industry • Texas beef industry • National Cattlemen’s Beef Assn • Major economic activity • 1995: 15.1 M cattle and calves; 6.2 M beef cows; total value of cattle and claves at $8.532 B; • Cash receipts of 1993 sales at $6.353 B • Texas: 111,875 jobs and $4.82 billion of personal income is generated from beef industry • Largest cattle state in US with 14.5% of 1994 inventory • No. 1 in number of farms and ranches (185,000) and total land (129.3 M acres) • Ex., Texas Beef: integrated ranching, farming and cattle feeding business • 100 years, four generations • Producing 200,000 cattle from two feed yards • http://www.tsha.utexas.edu/handbook/online/articles/RR/azr2.html

  4. Bovine: dairy and beef farming and industry • Ranching industry is different • Commercial feed lots, slaughter and meat-packing operations; computer-driven • Ostriches and zebras farmed

  5. Bovine: dairy and beef farming and industry • Traditional selection based on genetic merit calculated from phenotype and pedigree information • Tremendously successful at improving ‘production,’ such as in dairy cattle

  6. Beef farming and industry • Beef production • Black Angus

  7. Bovine breeding

  8. Bovine breeding: dairy • “year books” • Nitrogen storage and ‘straws’

  9. Bovine breeding: dairy

  10. Hypothetically, genetic improvement could be accelerated by selecting upon genetic differences • underlying phenotypes using ‘Granddaughter Design (GDD) as a method for ETL detection • Half-sib families • The Dairy Bull Repository is an example of one experimental GDD population established for ETL mapping • Eight of the largest NAmerican studs contributing semen for DNA extraction • 63 families with over 25 sons contained within 6,576 animals • Genome science to identify economic traits loci (ETL) • Resolve with respect to position on genome • Use DNA marker-based tests to enhance selection • (not “GM”) • TSSonstegard….MSAshwell. JAnimalSci. 2001. 79:E307-E315. Dairy cattle genomics: Tools to accelerate genetic improvement?

  11. Bovine breeding: updated with molecular data • To date, most dairy-related ETL have been analyzed in Holstein grandsire families • Marker intervals identifying ETL are not resolved well enough for accurate selection • ETL analyses are being extended to include ancestral animals that connect family pedigrees • As an aid to ETL mapping in dairy cattle, efforts to catalog as many bovine genes as possible • ESTs from cDNA clones; cDNA microarrays for gene expression patterns and pathways • that are important for animal production and udder health

  12. Bovine breeding: updated with molecular data • Heifers- “little princesses” • Potential mothers of more cows and day-to-day producers of milk • Mother is set for supply of milk for months • Genetic inheritance of bulls determine their fates • Want ones that sire daughters capable of reproducing easily and yielding quantities of milk • Screen for stud bulls among calves of only 1-2% of cows that are tops in milk production • Of the bulls making this cut, only 1 in 10 continue into active artificial insemination program • Can sire 80,000+ daughters, (even when dead) • http://www.sciencenews.org/articles/20041023/food.asp

  13. Bovine breeding: updated with molecular data • HDBlackburn, Ft. Collins USDA Natl Center for Genetic Resources Preservation • Holstein: 90% of all US dairy cows; intensively monitored, managed and documented • Decades-old semen samples: determine which genes in a Holstein line ~ milk production • 150,000 sample from cows, other mammals, birds and fish • Semen from 850 Holstein bulls, 150 embryos from 25 cows as gene bank • USDA, CvanTassell, maintains bigger dairy resource at Beltsville • 100,000 vials of semen from >15,000 bulls back to 1960 • One study (JTaylor/UMissouri), a Holstein pedigree for 1,000 related bulls going back 40 years • Milk production, fat production and protein production • Ex., chr6 identified as hotspot for genes affecting milk, fats and protein • Black Angus: beef breed • Screen bulls before breeding • http://www.sciencenews.org/articles/20041023/food.asp

  14. NAGRP: National Animal Genome Research Program • How genome is organized and expressed as traits • Sequences of livestock and poultry to understand how various genes function and interact • Spinoffs • Gene transfer, create new or altered strains of agriculturally important animals • Improved disease resistance, better growth rate and yield, improved reproduction and • Altered cell and tissue characteristics for biomedical research and manufacturing • Identifies quantitative trait loci (QTLs) associated with disease resistance or susceptibility • and production traits • Useful for selection strategies • Agricultural genomics: 1990 Farm Bill authorizing USDA National Genetics Resourse Program • Cattle, sheep, swine and poultry species; ‘recently’ horse and aquaculture • Sequencing the genome of cow, chicken, pig • Sequencing genomes of disease-associated microbes • 11/02: Mycobacterium paratuberculosis, Johne’s Disease in dairy cattle • Chronic and potentially fatal intestinal disorder in 8% beef herds and 22% dairy herds

  15. Bovine genome • Comparative alignment of bovine chr27, left, with partial transcript maps of hum chr48 • HSA4q and HSA8p • Estimated positions for loci given in cM • Genetic intervals containing human loci derived from radiation hybrid maps

  16. Porcine: pork farming and industry • National Pork Producers Council • ‘Sophisticated’ pipeline [?]

  17. Porcine: pork farming and industry • Corporate hog factories replacing traditional hog farms • 100 M pigs raised and slaughtered per year in US • Sows give birth and nurse their young in ‘furrowing crates’ • Nursing for 2-3 weeks then re-impregnated • http://falcon.tamucc.edu/~sencerz/anim-pigs.htm

  18. Porcine: pork farming and wastes • Smithfield Foods, the largest and most profitable pork processor in the world • Killed 27 M hogs in 2005; sales at $11.4 B • Under chairman JLuter, went from family business to “total vertical integration,” • controlling every stage of production to slaughterhouse, in 40 years • 500,000 hogs at a single subsidiary generate more fecal matter than 1.5 M inhabitants of Manhattan • Estimated at 26 M tons a year; stored in holding ponds, some 30 feet deep/120,000 sq ft • Containing urine, excrement, chemicals, drugs, blood, afterbirth and stillborn piglets • http://www.rollingstone.com/politics/story/12840743/porks_dirty_secret_the_nations_top_hog_producer_is_also_one_of_americas_worst_polluters

  19. Porcine: diseases and human disease • Foot and mouth disease, influenza, classical swine fever, porcine herpesviruses • 1976, mass vaccination after swine flu outbreak among army recruits at Fort Dix, NJ • 1918 influenza: hemagglutinin chimeric, from pig flu virus and human flu virus

  20. Pig genomics • USDA • European network for pig genomics • International Swine Genome Sequencing Consortium • Sino-Danish Pig Genome Project • 0.66x coverage/shotgun sequencing/3.8 M shotgun ladders • ~1 M EST sequences

  21. Pig genomics • KChen….LBSchook, et al. Int J Biol Sci. 2007 • “Genetic Resources, Genome Mapping and Evolutionary Genomics of the Pig (sus Scrofa)” • One of first animals domesticated, earliest remains in Anatolia 7,000 BC • Molecular markers used for genetic diversity and phylogenetic analysis in pigs • SSRs, AFLPs, SNPs and mtDNA genotpying • Sequence at 3x coverage; localization of genes on specific chromosomes, high density maps • 4,000 loci including 1,588 genes and 2,493 markers • Improving SNP discovery • Exploitation in breeding • BMote and MRothschild. Vertebrate Genomes. 2006 • “Cracking the Genomic Piggy Bank: Identifying Secrets of the Pig Genome” • 5,000 loci comprising genes, microsatellites, and RFLPs • Physical map with 6,000 markers • Candidate gene studies to correlate chromosomal regions and genes associated with economically • Important traits: growth rate, leanness, feed intake, meat quality, litter size and disease resistance

  22. Another aspect of pig genomics • NIH • Model organism for human disease • In lab ‘guinea pig’ • Obesity, cardiovascular diseases, organ transplantation

  23. Poultry farming • Chicken, turkey, duck, goose • Meat, eggs, feathers, fertilizer, [eggs in paint and vaccines] • Chicken • Breeding farms: meat • Arbor Acres, Ross and Peterson chickens • Alabama, Arkansas and Georgia • Layer farms: eggs • Rhode Island Reds and Leghorns • California, Indiana, Iowa, Ohio and Pennsylvania • Both meat and eggs • New Hampshires, Plymouth Rocks and Wyandottes • Turkey: Minnesota and North Carolina • http://library.thinkquest.org/TQ0312380/poultry.htm

  24. Poultry farming and wastes • Maryland and Delaware chicken farming, Delmarva industry • $1.5 B per year • “chicken and [proprietary] feed” owned by Perdue • Two large Delmarva chicken houses holding 11,500 birds each • 18,000 metric tons of airborne ammonia • Nutrient for plants • Fertilize algae in estuaries • Die, decompose in sediments, feeding microorganisms • Depletes oxygen from lower layers of water: “dead zones” • http://www.sciencenews.org/articles/20040424/food.asp

  25. Poultry farming and antibiotics use • JHU Public Health 2002 Magazine • ESilbegeld (JHU Environmental Health Sci); antibiotic-resistant bacteria • Maryland poultry house • Lights always on so the birds will eat continuously • Fine powdery dust of ammonia and manure • Seven weeks to optimum 5-lbs • Chicken feed mixed with tetracycline, penicillin and other antibiotics • Last 50 years to stave off infections and to promote growth in chicken, swine and cattle • 24.6 M lbs of antibiotics each for non-therapeutic purposes • Birds collected by hand • Hypothesized two routes of antibiotic-resistance: chickens and clinical use • Found Campylobacter jejuni, enterococci in workers • Molecular technology to track flow of resistance, using gene chip (SBiswal) • Genetic markers for antibiotic resistance in enterococcus • Including SNPs, VNTRs • http://www.jhsph.edu/Publications/Spring02/features.htm

  26. Chicken genome project, Dec 04

  27. Chicken EST libraries • WCarre…LACogburn, et al. Physiol Genomics 2006 • Chicken genomics resource: sequencing and annotation of 35,407 ESTs from • Single and multiple cDNA libraries • Several chicken EST projects give 517,727 public chicken ESTs and mRNAs

  28. Chicken EST libraries, unique genes • WCarre…LACogburn, et al. Physiol Genomics 2006 • CAP3 contigs show 96.7% match to chicken genome sequence • 6,223 unique ESTs with 76% match • Assembly of a chicken gene index • Identification of several nonredundant chicken gene sets for DNA microarrays

  29. “Building a Better Turkey Through Biotech” • 2003. UMinn and • Nicholas Turkey Breeding Farms, Sonoma CA • 690 M lbs turkey Thanksgiving 02; $3 B in annual US sales • First genome map of domestic turkey, Meleagris gallopavo • Mapped 100 genes (out of ~25,000) • Homology with chicken genome • Complete genome expected March 2004 • “Breed a better turkey” • Have been selectively red for white meat • Big-breasted birds that have trouble walking • Biotechnology to enhance breeding • removing guesswork of traditional methods • ex, using naturally occurring variations • Genetic resistance to certain diseases, bacteria, viruses • Plumper turkeys and juicier meat, eg strong leg muscles and bigger breast • Minimize cost and potential risks of preventive medications • Photo: http://www.genomenewsnetwork.org/articles/11_03/turkey.shtml • Title: http://www.livescience.com/animals/biotech_turkey_041124.html

  30. Avian flu and poultry farms • Naturally-occurring and bio-terrorism • Molecular diagnostics and forensics • VA poultry industry at $834 M • 8,000 to 25,000 birds per farm; some commercial turkey farms can hold 40,000 • 2/3 of state’s 1,200 poultry farms are in Shenandoah Valley • Rockingham County one of top three turkey-producing counties in US • VA considered progressive in its surveillance for avian influenza • WAPost 5/6/02 “Virginia Farmer…Avian Flu Outbreak Forces Slaughter of 3.2 M chickens, turkeys” • “…remains of the turkey house are smoldering.” “..to eradicate any traces of a raging influenza strain • that infected the coop’s 16,000 birds and forced their destruction a week before.” • Franwood Farms had to kill 100,000 infected turkeys • Pilgrim’s Pride reported $5.5 M in losses • Later total, 5 M birds destroyed due to low-pathogenic H7N2 avian influenza strain • Photo: http://www.avma.org/onlnews/javma/jul02/020701a.asp

  31. Infectious diseases of livestock • Naturally-occurring and bio-terrorism • Molecular diagnostics and forensics • Foot-and-mouth disease or hoof-and-mouth disease • Highly contagious, viral disease of cattle and pigs (plus) • Wide-spread and epidemic; economically devastating • Requiring slaughter of millions of animals, non-fatal disease • 2001, outbreak in UK via Type O pan Asia strain • 2,000 cases • 7 M sheep and cattle culled to halt disease/ $16 B cost • 2007, outbreak in UK via 01 BFS67-like virus (3 different outbreaks) • Not normally found in livestock, linked to vaccines, isolated in ‘67 outbreak • Same strain used at nearby Institute for Animal Health and Merial Animal Health Ltd, • 2.5 miles away: possible source of infection • Livestock culled; nationwide ban on movement of cattle and pigs • Postponing general election for a month • Rules regarding visitation of farms by travelers (at least for US) • Human infections extremely rare, FMD sensitive to stomach acid • wikipedia

  32. Recombinant DNA technology-based vaccines • Molecular-based treatment and prevention • First recombinant-based vaccines used in non-human subjects • Foot-and-mouth disease or hoof-and-mouth disease • Highly contagious, viral disease of cattle and pigs (plus) • Wide-spread and epidemic; economically devastating • Requiring slaughter of millions of animals • 1970s: vaccine could be made using a single key protein from virus • June 1981, first genetically engineered vaccine • Protection against foot and mouth disease by immunization with a chemically synthesized • Peptide predicted from the viral nucleotide sequence • JLBittle…FBrown, et al. Nature 82 • Isolated viral RNA; determined sequence of viral protein 1- major antigenic determinant • Synthesized peptides based on N- and C-termini • Inoculated rabbits and guinea pigs for antisera • New type of vaccine- does not depend on virus • Photo: wiki

  33. “ Gene therapy” [different applications/different ideas of…]

  34. Gene therapy and farming (aqua-culturing/farming) • NYTimes? 07

  35. Gene therapy and farming (aqua-culturing/farming) • Aqua Bounty Technologies • Growth hormone ‘on’ during summer months • Increase the ‘growing season,’ gene construct of • Chinook salmon growth hormone gene linked to • promoter of ocean pout antifreeze production • Into Atlantic salmon genome at egg stage • Trade name “AquAdvantage Bred” salmon • 4-6x faster growth • Applications to Arctic charr, trout, tilapia, turbot and halibut • http://www.aquabounty.com/research.html

  36. Transgenic salmon: “myths and facts” • Aqua Bounty Technologies • 1) Larger transgenic larger and out-competes native for food, space, sex • 10 years experience, no evidence transgenes grow larger than native; just reaches market size faster • No evidence farmed competes successfully with wild if escape; release of Atlantic salmon in Pacific • Unsuccessful in establishing population; in Atlantic, 130,000 escape but only 6 came back to spawn • 2) Interbreed with native- novel gene into the population [“Trojan Gene” theory] • Only sterile female transgenic salmon will be marketed; also above- no net advantage • 3) Sterilization may not be 100% • Triploidy produces 100% sterilization in female bec prevents ovary development; test for triploidy • 4) Transgenic salmon are voracious predators that will consume all available food and prey on juveniles • Transgenes prone to starvation, need to learn to identify and hunt wild food; higher metabolic rate • 5) Transgenic salmon produce antifreeze proteins and excessive amts of growth hormone • Only regulatory sequences fro antifreeze protein used; produce similar amts of hormone • but thru entire year

  37. Model organisms, genomics and Human biology

  38. Dog genome and Human biology • Dec 2005. KLindblad-Toh, et al • Boxer (Tasha) genome sequenced; • 7.6x at >98%; 2.4 B nucs/ 39 chr pairs • Also looked at DNA from 10 different breeds • 2.5 M SNPs • Standard poodle (Shadow) sequenced at 80% @2003 • Domesticated 15,000 years ago from the wolf (bottleneck) • [bottleneck as a reduction of genetic diversity] • Most breeds have recent origin, bottleneck of 50-200 years ago • Extensive phenotype data and pedigree data • Correlate genes to unique sets of traits, behaviors and diseases • Humans and dogs share 5% DNA, same % as mouse and human • Conserved sequences clustered around developmental genes • Dogs have >350 genetic disorders • Dogs and humans share many of the same lifestyles • Dogs and humans share many of the same diseases • Certain breeds associated with certain diseases • Diabetes, epilepsy, narcolepsy, cancers, allergies, retinal diseases and cataracts • Behavior traits such as aggression • Tool for finding homolog in humans • http://www.sciencedaily.com/videos/2006/0704-doggy_genes.htm • http://news.nationalgeographic.com/news/2005/12/1207_051207_dog_genome_2.html

  39. “ transgenic animals/knock-in and knock-out” Functional genomics (serendipity)

  40. Gene Therapy: “Super Mouse” • YXWong, REvans, et al. Oct 04 PLoSBiology. “Marathon” Mouse • Can run twice as far; endurance athlete • Increase in slow-twitch muscle; Resistant to weight gain • PPAR-delta, ‘master regulator’ gene- transformation in skeletal muscle fibers • (peroxisome proliferator-activated receptor delta) • Slow-twitch have larger numbers of mitochondria; Energy from fat rather than glucose • HansonRW, et al. Nov07 JBC. “Super Mouse” • Engineered mouse with abilities of a super athlete- 10x more active • Runs 6 km (3.7 mi) at 20 meters per minute for 5+ hrs without getting tired,, without stopping • Equivalent of a human cycling up an Alpine mountain without a break • Lives longer, increased sex drive, live longer, breeds into old age, eg 80 yo woman, eats more without getting fat • Very aggressive and eats 2x (-60x?) more food • Gene therapy for superior athletes?

  41. One gene difference: ‘Mighty Mouse’ • HansonRW, et al. Nov07 JBC. Engineered mouse with abilities of a super athlete- 10x more active • Overexpression of PEPCK • Runs 6 km (3.7 mi) at 20 meters per minute for 5+ hrs without getting tired, without stopping • Equivalent of a human cycling up an Alpine mountain without a break • Lives longer, increased sex drive, breeds into old age, eg 80yo woman • Very aggressive and eats 60x more food (without gaining weight) • Breeding colony of 500 • Same gene in human for more efficient fat metabolism, no lactic acid buildup • Muscles with 10x number of mitochondria • PEPCK-C, phosphoenolpyruvate carboxykinase: glucose metabolism and stimulates fat for energy • Glycolysis vs Kreb’s cycle; Committed step in gluconeogenesis: OAA to PEP when GTP is present • http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/gluconeo.htm

  42. “Genetically modified” athletes? • amateur • professional • GM-professional? • Molecular biotechnology protocols • Molecular biotech products • Cloning

  43. Social, legal [not ethical] limits to recombinant DNA-based technology to molecular-based technology

  44. Horse breeding • Domesticated 4,500 BC • Horse breeding; human-directed selected breeding, particularly purebred • For many purposes, excelling at specific tasks: • Arabian horse for speed and endurance; farm animal for plow and wagon, • Adapted for knight and armor warfare; ranch horses; racing and jumping • Wikipedia

  45. Racehorse breeding • Thoroughbred, ~1700 England from lines of 3 foundation Arabian stallions • In US, first true thoroughbred imported: Bulle Rock (1730) • Breeding follows Law of Supply and Demand • Stud fees range from $100-200 to $1,000-3,000 to $4,000 for one breeding • Thoroughbred industry requires all registered foals to be bred through live cover, • eg, not by artificial insemination (AI) • despite risks • Standardbred industry allows AI but only fresh or frozen, not dried, semen; • Semen collected during stallion lifetime and • used no later than a year after death or castration • Wikipedia • http://sports.espn.go.com/sports/horse/index

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