Genetic Defects: Current Status and Breeding Management

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Genetic DefectsCurrent Status and Breeding
Management

• Jon Beever
• Brown Bagger Series
• October 14, 2009

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background

• Most genetic defects are going to have recessive
  patterns of inheritance
• not problematic if present at a low allele
  frequencies
• commercial cross-breeding programs have less risk
• Recognition of genetic defects typically occurs
  after it is too late
• allele frequency is sufficiently high to cause
  consistent frequency of affected calves
• threat proportional to population size

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solution

• New genomic technologies insure rapid solutions
  to emerging problems
• short- to mid-term time frame for the
  identification of causative genes/mutations
• development of DNA-based tests
• assembly of sufficient material short-term
  success
• high accuracy
• cost effective
• breeding decisions assisted by molecular tools
• potential for elimination of deleterious mutation
  without loss of valuable germplasm

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genetic defects

• Idiopathic Epilepsy (IE)
• Arthrogryposis Multiplex (AM)
• Hypotrichosis (HY)
• Neuropathic Hydrocephalus (NH)
• Osteopetrosis (OS)
• Fawn Calf Syndrome (FCS)

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Idiopathic Epilepsy (IE)

• Generalized seizure disorder
• neurologic
• Parkinsons-like locking up syndrome
• Origin in Hereford cattle
• Putative proband born circa 1982
• DNA-based test released in January 2008
• more than 18,000 cattle tested to date
• relatively low frequency lt2
• has been observed in baldie based commercial
  operations

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AM phenotype

• arthrogryposis
• scoliosis/kyphosis
• muscular hypoplasia

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current status

• Research initiated in September 2008
• DNA test released December 15, 2008
• Relatively high allele frequency
• 8 in AI sires slightly higher in cow herd
• Rapid implementation
• 80,000 registered animals tested
• Long-term policies in place
• ability to secure high merit genetics
• eventual reduction in frequency or elimination

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Osteopetrosis (OS)

• Commonly referred to as marble bone disease
• late term abortion, small body size
• 240 to 275 days
• brachygnathia (parrot mouth)
• may be accompanied by other skull malformations
• brittle, dense bones
• no marrow cavities (solid bones)
• reported in both Angus, Red Angus and Hereford
  present prior to 1970

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• Red Angus diagnostic developed
• collaboration between USDA MARC BARC, UNL, UW
  and UI
• announcement of confirmed carriers by RAAA on
  March 17, 2009
• Low/moderate frequency
• probably between 1.5 to 3
• Currently not recommended for use in breeds other
  than Red Angus
• continued investigation into Black Angus mutation

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Neuropathic Hydrocephalus (NH)

• Invariably lethal
• high estimated embryonic and fetal losses
• Generalized absence of central nervous system
  tissue
• pronounced hydrocephalus
• arthrogryposis and muscular hypoplasia
• DNA-based test released in
• Spring 2009
• Also relatively high
  frequency
• 10

courtesy of David Steffen, UNL
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Hypotrichosis (HY)

• partial absence of hair at birth
• predominantly a Polled Hereford issue
• stems from early 60s proband
• diagnostic developed and currently being deployed
• low/moderate frequency

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Fawn Calf Syndrome (FCS)

• Semi-lethal
• joint laxity/contractures
• connective tissue
• Recessive inheritance
• confirmed by WGA/
• homozygosity analysis
• 18 calves 1.5 Mb interval
• Gene identified
• preliminary test shows low frequency
• DNA-test available soon

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how accurate are the tests?

• Two major components to accuracy
• scientific basis and testing process/execution
• Tests are based on specific mutations associated
  with each genetic defect
• tests do not use linked or associated changes
  in the DNA
• Testing process starts at sample collection and
  ends at reporting

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breeding management

• Expense vs. outcome
• low cost no affected calves born
• sires only no affected calves born to
  genetically free sires
• moderate cost on the road to elimination
• sires, herd matriarchs and annual replacement
  heifers
• highest cost complete management
• all animals in the herd
• does not imply elimination, only management

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recessive inheritance

• A mating using at least one free (AA) parent
• Free parent can only produce A gametes
• No affected offspring produced
• 5050

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should I use carrier animals?

• Are there other defect-free animals with equal
  genetic value?
• Is it worth the /opportunity cost?
• Is your management good enough?
• What is the purpose of retaining carriers?
• How important is it to eliminate defects from the
  population?

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implementation

• Differs based on place in production system
• Seedstock
• highest management
• Commercial with replacement
• commitment to manage female base
• Commercial terminal
• little or no risk

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future directions

• education
• the psychology of breeders toward genetic defects
• industry wide standard reporting processes
  reimplementation of old protocols
• central location(s) for establishing collections
  for DNA analysis

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summary

• genetic defect research should be viewed as
  preventative investment
• solutions can be very rapid
• must have a proactive and positive attitude
  toward defect surveillance and reporting