Genetic Defects: Current Status and Breeding Management

1. Genetic Defects:Current Status and Breeding Management Jon Beever Brown Bagger Series October 14, 2009

2. 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 background

3. 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 solution

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

5. Generalized “seizure” disorder • neurologic • Parkinson’s-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 – <2% • has been observed in “baldie” based commercial operations Idiopathic Epilepsy (IE)

6. arthrogryposis • scoliosis/kyphosis • muscular hypoplasia AM phenotype

7. 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 current status

8. 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 Osteopetrosis (OS)

9. 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

10. 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% Neuropathic Hydrocephalus (NH) courtesy of David Steffen, UNL

11. 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 Hypotrichosis (HY)

12. 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 Fawn Calf Syndrome (FCS)

13. 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 how accurate are the tests?

14. 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 breeding management

15. A mating using at least one free (AA) parent • Free parent can only produce A gametes • No affected offspring produced • 50:50 male parent gametes A A AA AA A 25% 25% female parent gametes Aa Aa a recessive inheritance 25% 25%

16. 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? should I use carrier animals?

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

18. 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 future directions

19. 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 summary