What's
in the Genes?
Reprinted with permission of U C Davis
For those of
us who love horses, recognizing various traits specific to particular
breeds is a game we enjoy. Those who are experts of a certain breed
can often recognize traits that are characteristic of a particular
pedigree. How do these characteristics pass from generation to generation?
Many traits
are inherited; "it's all in the genes," as they say. But how do
we identify the individual genes and then predict which ones will
be passed on, both good and bad? That's where it gets a little more
complicated and we must rely on the research conducted by genetic
experts.
Overview
of Genes
Genes are the individual components of the very large and complex
DNA (deoxyribonucleic acid) molecules that are found in the nucleus
of every living cell. Genes encode information that directs the
manufacture of proteins that maintain all normal body functions.
The DNA molecule is in the shape of a twisted ladder called a double
helix. The rungs of the ladder consist of four bases: adenine (A),
thymine (T), guanine (G) and cytosine (C). These bases bond together
following specific rules. A always bonds with T and G always bonds
with C. These bonds form specific patterns like words and sentences.
The "sentences" are the genes that direct the manufacture of various
proteins. The DNA is packaged into compact units called chromosomes
within the nucleus of every cell. Equine DNA is packaged in 64 chromosomes.
The basics of
inheritance were first clearly defined by the Austrian monk and
naturalist Gregor Mendel (1822-1884) in his studies of garden peas.
Each gene contains two alleles, one on each chromosome of a chromosome
pair. One allele is inherited from the mother, the other from the
father. Since each child receives one half of their genes from their
mother and the other half from their father, the mixing of these
two sets of genes occurs in many different combinations.
Alleles can
be dominant or recessive. A dominant allele is one that is expressed
even when the chromosome pair contains one allele of each. For example,
black coat color is said to be dominant to red coat color. The presence
of just one dominant allele (coding for black hair) will result
in a black coat, even if the red allele is present as the other
member of the chromosome pair. The coat color can only be red when
both members of a chromosome pair contain the recessive red allele.
Because the chromosomes bearing the genes occur in pairs, the coat
color will be determined by the interaction of the allele pairs.
|
Heterozygous
Stallion (Ee) - Black
|
| |
E
|
e |
| E |
EE
- 25%
Black
(no red carrier) |
Ee
- 25%
Black
(red carrier) |
| e |
Ee
- 25%
Black
(red carrier) |
ee
- 25%
Red |
|
| Heterozygous
Mare (Ee) - Black |
The genotype
is used for the letter symbols describing a gene pair. Therefore,
if "E" stands for black coat color and "e" for red coat color, then
the genotype of all black horses will be either EE or Ee and all
chestnut horses will be ee. When both alleles in a pair are the
same (EE or ee), the horse is said to be homozygous for that trait.
When each of the two alleles is different (Ee), the horse is said
to be heterozygous for that trait. Two black horses can produce
a chestnut if the parents are heterozygous as shown in this Punnett
square diagram.
Inherited Diseases
Recent advances in molecular genetics provide the groundwork to
develop genetic tests for the diagnosis and prevention of inherited
diseases. Inherited diseases are caused by mutations or changes
in the DNA of the affected individual. The mutations or changes
can be single base pair changes, DNA insertions, DNA deletions,
or DNA rearrangements. The goal behind the molecular genetic analysis
of inherited diseases is to define the mutation that causes a particular
disease and then design a test specific for that mutation.
For example,
Lethal
White Overo Syndrome occurs in spotted horses and results
in an all white foal with intestinal abnormalities. These foals
die shortly after birth. Researchers identified that in these lethal
whites, a receptor gene contains a change in the order of the basic
DNA building blocks (thymine/cytosine to adenine/guanine), which
results in a mutation that affects the normal development of the
intestine.
Dr.
Danika Metallinos Bannasch, now an assistant professor at
the University of California Davis School of Veterinary Medicine,
developed the genetic test for lethal whites while she was a UC
Davis veterinary student. By examining a horse's DNA, which is easily
obtained from a sample of mane hair, blood or saliva, researchers
can identify the matching genetic code to identify carriers of the
disease as well as affected foals.
Another example
is Hyperkalemic Periodic Paralysis (HYPP) in Quarter Horses, which
is caused by a defect in the sodium potassium channel within the
muscle cells. The disease results in varying levels of muscle tremors,
shaking, weakness and sometimes collapse. In some cases, sudden
death can occur following a severe paralytic attack, presumably
from heart failure or respiratory muscle paralysis. Dr. Sharon Spier,
an associate professor at the UC Davis School of Veterinary Medicine,
was able to trace the disease back to the original carrier and then
develop a genetic test to identify both carriers and affected horses.
Current Research
UC Davis researchers are directing their efforts towards clarifying
the molecular basis of inherited diseases. Many diseases that affect
purebred animals have a heritable basis. Researchers are very interested
in developing tests to help breeders eliminate inherited diseases
in horses and dogs. Characterizing inherited diseases in animals
has the added benefit of providing an animal model for human diseases.
Currently, UC
Davis researchers are investigating the genetics of an inherited
skin disease in Quarter Horses and horses with Quarter Horse lineage
(Paints and Appaloosas). The disease known as Hereditary Regional
Dermal Asthenia (HERDA) causes the skin along the horse's back and
neck to stretch and tear easily, making the horse unusable for riding.
HERDA is most commonly recognized in young horses when they begin
their training to ride. The site where the saddle is placed develops
wounds that don't heal easily. Often, these horses have a history
of slow or poorly healing wounds.
A UC Davis research
team headed by Dr. Stephen White hopes to determine how the disease
is inherited so they can provide better breeding recommendations
to avoid passing this disease to others. The team is also studying
skin biopsies of affected horses using a variety of staining techniques.
If researchers can identify candidate genes, then they can develop
a genetic test to identify this disease.
A UC Davis research
team headed by Dr. Cecelia Penedo is also studying the genetics
of Cerebellar Abiotrophy, a neurological disease in Arabians. This
disease causes a progressive loss of function in the cerebellum
(the portion of the brain concerned with motor function, balance
and coordination of movement). This degeneration results in a lack
of coordination, imbalance and head tremors. The symptoms generally
do not occur until the foal is several weeks old. The gait becomes
exaggerated and the foal will stand with its legs wide apart. Early
signs also include crashing into fences and falling over backwards.
Once the genetic basis can be identified, researchers hope to develop
a genetic test to identify the disease and help breeders make informed
decisions to avoid the disease.
Enteroliths
(intestinal stones) are the number one cause of colic requiring
surgical intervention throughout the world. The UC Davis School
of Veterinary Medicine's Gastroenterology Laboratory, headed by
Dr. Jack Snyder, is utilizing sensitive molecular techniques to
identify and characterize the genetic processes associated with
enterolith formation. This information will help researchers develop
strategies for prevention and treatment.
Allergic conditions
in horses can be very debilitating and even render a horse unfit
for riding or competition. UC Davis researcher Dr. Johanna Watson
is studying the genetics of allergic disease in horses in hopes
of developing a diagnostic test and preventive strategies (see page
10). She is discovering that the genetics of allergic conditions
is very complex and most likely caused by the interaction of multiple
genes. Using the latest in genetic technology, she hopes to develop
diagnostic tests so allergic conditions could be identified early
on and then therapy could be initiated before permanent lung damage
occurs. A genetic test to identify horses with allergic conditions
would also help breeders screen sires and dams prior to breeding.
Equine protozoal
myeloencephalitis (EPM) is a progressive neurological disease caused
by protozoal parasites. EPM is the most common disorder affecting
the nervous system of horses in the United States. UC Davis researchers
led by Dr. David Wilson are investigating the genetics of this disease
to understand how the horse's immune mechanisms respond to the infection,
and how the horse's immune system recovers and then protects itself
from further infection. Dr. Patricia Conrad, another member of the
EPM research team, will also use this information to develop improved
diagnostic tests.
Another UC Davis
scientist, Dr. Alain Theon, is studying the genetics of cancerous
skin tumors in horses. His goal is to develop a vaccine using tumor
cells from affected horses. The idea is to utilize the horse's own
immune system to destroy the cancer cells in the skin tumors.
Gene mapping
involves identifying particular genes for specific traits. UC Davis
geneticists, originally led by the late Dr. Ann Bowling and now
in collaboration with equine researchers throughout the world, are
constructing comparative genetic maps for horses, dogs and cats.
An equine gene map could provide horse breeders with genetic tools
to select animals with desirable traits. Gene linkage maps can also
be used to identify likely candidate genes described from other
mammals that may lead to a direct test for a particular gene in
horses.
Genetic Testing
The UC Davis Veterinary Genetics Laboratory (VGL) is the largest
equine blood typing facility in the world. Dr. Marcia Eggleston,
the executive associate director, estimates that last year alone,
nearly 140,000 horses were typed and she says the lab currently
has about 650,000 individual horse samples on hand. The VGL provides
services to breed registries, practitioners and individual owners
and breeders.
In the past,
blood typing of domestic animals provided an excellent means of
validating pedigrees, solving parentage in multiple sire breedings
and providing identification of individual animals. However, while
blood typing is still used in routine assays, DNA typing is rapidly
replacing blood typing because it is faster, offers higher efficacy
and provides additional capabilities for genetic research. DNA tests
detect changes in genomic sequences and produce a DNA fingerprint
unique to each individual animal.
Recently, the
VGL has made significant advances in equine parentage verification
using the latest technology. The VGL is now an international leader
in automated DNA analysis and computerized data management. DNA-based
genetic tests are no longer restricted to blood samples. For live
animals, collecting hair roots or semen offers a non-invasive sampling
procedure.
While the majority
of cases handled by VGL are standard equine parentage verifications,
the lab has developed additional protocols patterned after those
utilized in human forensics. These are applied to the occasional
stolen horse or dead horse cases. For dead animals, DNA analyses
can be performed on muscle, skin, bone, or teeth submitted for testing.
In one case, a racing commission utilized the VGL to verify that
an inhaler had been used to administer epinephrine, a prohibited
substance in racing, to a racehorse. The VGL was able to identify
equine DNA in the mucous found on the inhaler. This information
was passed on to racing officials to alert them for this new form
of delivering a prohibited substance to racehorses.
The VGL currently
offers genetic testing, not only for parentage verification, but
also for diseases such as HYPP in Quarter Horses, Lethal White Overo
Syndrome in spotted breeds (Paints, etc), and neonatal isoerythrolysis
in mules. They also offer genetic tests for coat color including
red coat factor and tobiano (spotted horse pattern).
The UC Davis
School of Veterinary Medicine also offers a Genetics Service to
the public. This relatively new service is one of only a few such
programs in the United States, according to Dr. Danika Bannasch
who is heading the program. The service was designed to help animal
owners find out more about inherited diseases, especially in purebred
dogs, cats and horses. The service offers consultations with breeders
and veterinarians to help diagnose genetic conditions. The diagnosis
may involve pedigree analysis or DNA testing and genetic counseling.
The VGL may assist with parentage testing or pedigree analysis and
disease testing. For more information on the Genetics Service or
to make a consultation appointment, contact (530) 752-0290
for large animals and (530) 752-1393 for small animals.
Genetics is
a multifaceted complex field of study. Thankfully, there are researchers
who are fascinated and captivated by the challenge of discovering
what's in the genes. With the development of new technology and
methodology, researchers are now discovering more and more about
how diseases are inherited, how they affect the body and how the
body protects itself. With this information, scientists hope to
develop diagnostic tests for genetic conditions. These tests will
provide breeders with information to avoid crossing horses that
may pass on disease and will provide veterinarians with an early
and accurate diagnosis of various conditions. Once a diagnosis is
made, then an owner can decide on possible treatments or a change
in career for the horse. The genetic studies also provide veterinary
clinicians with information on diseases so that appropriate treatment
or preventive modalities can be designed.
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HELPFUL
TIPS
|
Equine
Genetic Testing
|
|
 Veterinary
Genetics Laboratory
http://www.vgl.ucdavis.edu/
or call 530-752-2211
- Parentage
Verification
- DNA
Typing
- Crossmatching
(blood crossmatching services)
- Karyotyping
(chromosomal abnormalities)
- Lethal
White Overo Syndrome (disease in Paints)
- Hyperkalemic
Periodic Paralysis or HYPP (disease in Quarter Horses)
- Neonatal
Isoerythrolysis (disease in mules)
- Coat
color: Red Factor test and Tobiano (spotted pattern)
UC
Davis School of Veterinary Medicine Genetics Service
www.vetmed.ucdavis.edu/CCAH/Genetics/Default.htm
or call 530-752-0290
Consultation
services available for:
- Lethal
White Overo Syndrome
- Hyperkalemic
Periodic Paralysis or HYPP
- Severe
Combined Immunodeficiency or SCID (disease in Arabian
foals)
|
|
The Horse Report is Copyrighted © 2001-2002
by the Regents of the University of California. Use of this material
for re-publication is allowed only by permission of the Center for
Equine Health.
