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Download Dealing with Recessive Genetic Defects
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Genetic Defects: Current Status and Breeding Management Jon Beever Brown Bagger Series October 14, 2009 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 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 Idiopathic Epilepsy (IE) Arthrogryposis Multiplex (AM) Hypotrichosis (HY) Neuropathic Hydrocephalus (NH) Osteopetrosis (OS) Fawn Calf Syndrome (FCS) genetic defects 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) ◦ arthrogryposis ◦ scoliosis/kyphosis ◦ muscular hypoplasia AM phenotype 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 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) 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 Invariably lethal Generalized absence of central nervous system tissue ◦ high estimated embryonic and fetal losses ◦ pronounced hydrocephalus ◦ arthrogryposis and muscular hypoplasia DNA-based test released in Spring 2009 Also relatively high frequency ◦ ~10% courtesy of David Steffen, UNL Neuropathic Hydrocephalus (NH) 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) 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) 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? 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 female parent gametes male parent gametes A a A A AA AA 25% 25% Aa Aa 25% 25% A mating using at least one free (AA) parent Free parent can only produce A gametes No affected offspring produced 50:50 recessive inheritance 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? 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 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 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