April/May 2008 Issue (pdf - 7794 kb)... - Hereford America

16 • www.herefordamerica.com HEREFORD AMERICA • April/May 2008
Epilepsy (IE) Explained By Lead Researcher
by Jonathan E. Beever, Ph.D.
Associate Professor of Molecular Genetics
Department of Animal Sciences
University of Illinois at Urbana-
Champaign
Editor’s Note: Hereford America asked Dr.
Beever to write an article explaining the
epilepsy issue (IE) in Hereford cattle. He is
the lead researcher on this subject and is the
researcher who identified the IE gene. Thank
you to Dr. Beever to take the time out of his
busy schedule to answer a few questions.
Q: What is Idiopathic Epilepsy (IE)
in Hereford cattle?
IE is a recessive genetic defect with
a variable age of onset (occurrence of
the first seizure) ranging from birth to
several months of age. Occurrence and
Sale catalog will be in the May issue of
Hereford World or contact National Cattle
Services, (580) 492-4590 or
Jimmie & Darla Johnson, (580) 323-2774
persistence of seizures may be
influenced by environmental stressors
such as temperature extremes (e.g.,
extreme cold during calving) or
increased physical activity (e.g.,
processing at vaccination or weaning).
Upon initial onset of seizures calves
may appear to walk with a stiffened,
irregular gait. During seizure episodes
individuals will typically lie on their
side with all limbs extended in a rigid
state. Seizure episodes may last from
several minutes to more than an hour.
Affected calves typically have a high
mortality rate. To date, no anatomic
abnormalities or histologic lesions have
been detected following necropsy of
affected calves.
Jimmie & Darla Johnson
4600 W. Modelle
Clinton, Oklahoma 73601
Home: (580) 323-2774
Cell: (580) 331-8534
Dustin Hoffman, Manager
E-mail:
gptservice@sbcglobal.net • Web site: www.redhillsherefords.com
Q: What research has been
conducted to find a DNA test for IE?
Over the past four years the
University of Illinois and the American
Hereford Association have been
involved in a joint research project
aimed at determining the genetic cause
of IE. This has involved working
directly with a number of breeders who
have been willing to provide DNA
samples on animals that had produced
calves affected with IE or directly from
IE affected calves. As of April 2007,
enough data had been obtained to
clearly demonstrate that the condition
was of genetic origin. Additionally, a
collection of DNA samples sufficient
to map the gene and potentially identify
Watch for
Sale Catalog in
the May issue of
Hereford World
or contact us
for a copy.
the causative mutation was completed.
By August of 2007, the gene causing
IE had been mapped to a single cattle
chromosome and the DNA sequencing
of individual genes was initiated. In
early January 2008, a mutation was
identified that was thought to cause IE.
A diagnostic assay has been developed
based in this mutation and is now being
used to screen animals submitted
directly by individual Hereford
breeders.
Q: How accurate is the DNA test
for IE?
There are two distinct components that
contribute to the accuracy of any DNA
test. The first component involves the
scientific data that underlie the test.
The second component is the design
and execution of the diagnostic assay
performed as part of the testing
procedure. From a scientific standpoint,
the IE test is based on the presence of a
specific change or mutation in the DNA
sequence of an animal. This change
occurs within a gene (i.e., a sequence
in the DNA that encodes a protein) that
is expressed in the nervous system of
the animal. The mutation results in the
production of a protein that is unable
to carry out its normal function. An
example of how this happens can be
demonstrated by comparing this protein
to a simple sentence composed of three
letter words, THE CAT SAW THE DOG.
If a single letter (M) is inserted within
these words, as in the case of the IE
mutation, then the new sentence (i.e.,
containing the insertion) would be THE
CMA TSA WTH EDO G. Clearly, the
sentence, like the protein, does not have
the same meaning after the change has
occurred.
After identifying the specific
mutation, several experiments were
conducted to validate the relationship
between the mutation and IE. Two types
of validation experiments were
performed which included the blind
testing of animals with previously
known IE status and analyzing the
frequency of the mutation among
unaffected cattle within the Hereford
and other beef breeds. In all validations,
the test performed as expected. All
blind samples were correctly classified
by the test in accordance with their
known IE status. Additionally, no
unaffected animal tested as
homozygous for the mutation and the
mutation was only found in lines of
cattle that had produced affected IE
calves. The mutation was also not
found in any of the other breeds of
cattle examined. Therefore, we believe
that the scientific basis of the test is
accurate; in other words, testing for this
specific mutation will lead to correct
classification of any animal.
In regard to the diagnostic assay that
is used for determining an animal’s IE
status, the test has undergone several
optimizations that also lead us to