Page 73 - October 2016

Tracking The MuTaTion
After identifying the mutation, Valberg and her colleagues set out to determine
how GBED was inherited. They studied 11 Quarter Horse foals that had similar symp- toms, looking at their DNA. They also evalu- ated the DNA of eight of their dams, six of the sires, three half-siblings, and one full sib- ling, and compared these findings with DNA from 16 healthy, unrelated Quarter Horses. The AQHA funded the research, wanting to determine if this disease was a problem in their breed.
The researchers learned that GBED was caused by a recessive gene—a genetic defect that only appeared in offspring that inherited the mutated gene from each parent. All of the foals that died from GBED were homozygous for this defect; they received it from both sire and dam. All the parents tested were hetero- zygous carriers, meaning they each had one normal gene and one defective gene (mutated copy). All of the siblings tested carried just one copy, or none. None of the control horses car- ried the mutation.
Both the sire and dam must be carriers of the hidden trait in order for it to crop up in the foal. A horse that inherits just one copy
of the gene will not exhibit the defect, but is
a carrier and could produce an affected foal
if mated with another carrier. If a carrier is mated to a normal horse that does not have the recessive gene, the offspring will have a 50% chance of inheriting the recessive gene and would thus be carriers, but none of them would be affected with GBED themselves. But when a carrier is mated to another carrier, each of them has a 50% chance of passing along the recessive gene and, thus, the foal
A foal with GBED cannot efficiently store and metabolize glucose and, therefore, his muscle cells run out of energy andbecome weak, resulting in seizures and death.
would have a 50% chance of being a carrier, a 25% chance of inheriting the gene from both parents (and, thus, be affected with GBED) and a 25% chance of not receiving the defec- tive gene at all.
All of the affected foals in the University of Minnesota study were Quarter Horses and all of them were related, but not necessarily closely related. They all had some shared ancestors, but in some instances these mutual ancestors were back as far as nine generations. Pedigree analysis eventually traced it back to the
Both the sire and dam must be carriers of the hidden trait in order for it to crop up in the foal.
Quarter Horse foundation stallion King, who was born in 1932. He sired 658 registered foals, including 20 AQHA Champions. None of his foals would have exhibited GBED because they needed to have two copies of the gene in order to be affected, and only 50% of his offspring would have ended up as carriers. But, some of his descendants were the result of inbreeding or linebreeding, doubling up the mutated gene, and that’s when GBED first appeared.
Dr. Valberg estimates that about 8% of King’s descendants today carry this mutated gene. To trace it back to King, she first looked to see if there were any similar ancestors in the affected foals she was studying. She found that all but one descended from King. One foal had to be traced back to King’s sire, Zantanon, to link both its sire and dam.
The only way to know if the horses descended from King are carriers of GBED is to test their DNA and find out if they possess the mutated gene. Valberg feels that horses descending from this bloodline should be tested if they sired or carried foals that were lost to abortions or died young for any unknown reason. If horse breeders test their animals and choose not to mate carriers to carriers, there would be no more GBED foals produced.
SyMpToMS and diagnoSiS
Some GBED foals die in late gestation and are aborted. Others are full term, but dead at birth. Those that are born alive show a wide variety of symptoms, which include being underweight/smaller than normal at
Pedigree analysis traced all of the affected foals back to the Quarter Horse foundation sire King, some of whose descendants were the result of inbreeding or linebreeding and that doubled the mutated gene which is when GBED first appeared.
birth; having low body temperature and muscle weakness; being unable to stand and nurse, especially if the foal is lying on its side; and rapid breathing. They may also be born with contracted tendons in all four legs. The outward signs may arise from which- ever body tissues are most affected by the limited supply of glycogen. If a veterinarian takes a blood sample to evaluate, the GBED foal often has a low white blood count, or low blood glucose levels and high muscle enzymes (CK and AST) and high levels of the liver enzyme GGT.
If the foal is weak at birth, it may get stron- ger for a while if tubed with colostrum and helped to stand and nurse, but it may later die suddenly if the heart stops due to inadequate energy for the heart muscle or from seizures due to low blood sugar. High respiration rate is a common sign if the breathing muscles are weak. Many foals are not as active as normal due to weakness of the skeletal muscles.
This genetic disease is more common than we realize since it is often mistaken for some other disease. Valberg points out that it can easily be confused with an infection such as septicemia (common in young foals) or neona- tal maladjustment, or hypothyroidism (a prob- lem in newborn foals that causes contracted tendons). Some affected foals are euthanized because they become progressively weaker and eventually cannot get up without assistance.
Even if postmortem examination is done when a foal dies mysteriously, GBED may not be detected. The body tissues are usually examined with a stain called H&E
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