The blueprints for the structure of every life from, and the instructions for the activity of its every cell, are found within its genes, which are made up of DNA (deoxyribonucleic acid). The familiar double-helix-shaped molecule is made of two chains of nucleotides--adenine (A), cytosine (C), guanine (G) and thymine (T).
These nucleotides are grouped into sets of three (ACG, CGG, TCA, for example), called codons, that, when activated (expressed), ultimately code for the production of an amino acid.
The problems arrive when there is an error in the sequence of nucleotides.
"A change in the sequence of letters, or when one letter is dropped, can change the function of the gene," says Stephanie Valberg, DVM, PhD, of the University of Minnesota. "If the first letter in the chain is dropped, then the cellular machinery reads the sequence out of sync affecting which type of amino acid is produced."
As a result, the protein coded by the mutated gene may not have the correct amino acid sequence or the protein may not be produced at all. In either case, the function of the protein may be altered which can effect the animal's survival.
"Proteins, particularly enzymes, depend on a three-dimensional shape to function and a change in the amino acid structure can change that," says Gus Cothran, PhD, of the Equine Genetics Lab at Texas A&M University. "The protein may not work efficiently or protein production can stop entirely, leading to major problems."
Mutations--random changes in the nucleotide sequence--occur constantly when the DNA replicates itself during cell division (or when the DNA is damaged, by radiation, chemical exposure, etc.) Most do little if any harm, but a mutation that disrupts a critical function, and that can be passed on to descendants, will become a new genetic disease.
Not all horses who possess a mutated gene express clinical signs of disease. Genes occur in pairs that perform the same function (govern eye color, for example), but the activity of one may dominate (dominant gene) the activity of the other (recessive gene); a pair of genes may also be co-dominant, meaning that each contributes equally to the resulting trait. When a disease is dominant, only one copy of the dominant gene is necessary for disease expression. When a horse with a dominant trait is bred to a healthy horse there is a 50 percent chance of that offspring developing the disease.
If the mutated gene is recessive, two copies are required to express the disease. A horse with one copy of the mutated gene will be completely normal--he will be a "carrier" of the disease. But when he reproduces, there will be a 50-50 chance that he will pass the mutated gene on to his offspring. If the foal receives a recessive gene from both parents, then there will be no healthy dominant counterpart to take over that gene's function, and the foal will experience the disease.
If a carrier mates with a noncarrier, each foal has a 50-50 chance of either becoming a new carrier or of inheriting two healthy genes. But, when two carriers mate, each has the potential to pass on the mutation, so the resulting foal has a 25 percent chance of inheriting only the two healthy genes, a 50 percent chance of becoming a new carrier of one mutated gene, and a 25 percent chance of getting both mutations and acquiring the disease.
To read more about equine genetic diseases, see "Genetic Tests" in the February 2007 issue of EQUUS magazine.