Transcript Dealing with Recessive Genetic Defects

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