Use of results

It can be shocking to see it in print – evidence that your horse is positive for the genetic risk variants for Muscle Integrity Myopathy (MIM, previously called “PSSM2”). However, these results will give you the ability to support your horse and adapt management strategies to minimize symptoms.

Inheritance: incomplete autosomal dominant / semidominant with incomplete penetrance

This type of inheritance is typical in complex hereditary diseases and applies to all known variants of hereditary myopathy/training intolerance.

 It means that even a single altered gene copy (heterozygosity) can be sufficient to lead to a horse developing symptoms.

If both copies of the single gene are altered (homozygosity), the risk increases. This affects both the likelihood of the symptoms developing and their intensity.

The "amplification effect" also occurs when different variants come together in any combination.

 Incomplete penetrance ('penetration') means that the symptoms do not necessarily occur. Diet, training condition and other (as yet unknown) genetic mutations can moderate the effect of the variants.

The following genotypes and effects apply for the variants P2, P3, P4, Px, P8, K1.

n/n = normal (no mutation)

The horse has no increased risk of developing symptoms of PSSM2 because of this variant. The risk of the offspring developing symptoms is not increased through this parent.

n/P* = Heterozygous for the variant

The horse has one normal and one mutated copy of the variant. The mutation results in the protein not being correctly produced in the body, which is why it can cause or intensify the symptoms of myopathy. The normal copy of the variant can somewhat compensate for the function of the mutated copy, with varying levels of success. In the absence of additional stress factors (other genetic variants or environmental factors), the compensation by the normal copy may be sufficient for the animal to show only minimal symptom. The presence of stress factors or triggers of negative nitrogen balance can overwhelm this compensation and result in the animal having more severe symptoms.

For each variant there is a 50% chance that it will be passed on to the offspring.  The risk of the offspring developing symptoms depends on which and how many variant(s) the other parent also contributes.

P*/P* = Homozygous for the variant 

The horse has two mutated copies of the variant. The mutation results in the protein not being correctly produced in the body, which is why it can cause or intensify the symptoms of myopathy. There is no normal copy of the protein to take over the function, which is why a homozygous animal usually has more severe symptoms than a heterozygote.

For each variant there is a 100% chance that it will be passed on to the offspring. The risk of the offspring developing symptoms depends on which and how many variant(s) the other parent also contributes.

It is important to understand that there can be other causes of the symptoms of exertional myopathy.

These include forms of lameness caused by joint or tendon problems, laminitis, malformations of vertebrae (eg. Equine Complex Vertebral Malformation “ECVM”), neurological diseases, mineral deficitencies, other genetic diseases (MHY1-myopathy, PSSM1, MH), or infections (eg. New Equine Virus, NEV). Management issues and over-training may also cause similar symptoms.