DNA tests

Many diseases are caused by small mutations in the DNA. We've seen that DNA contains the recipes for all kinds of proteins (enzymes) that enable chemical reactions. This way essential parts of cells are created. When the DNA is changed the enzymes may function differently or stop working altogether. Tests have been developed to detect the changed genes. Below you'll find a list of diseases which can occur in Border Collies and for which currently DNA tests are available.

Collie Eye Anomaly (CEA)

CEA is an eye defect in several breeds and is characterized by possible defects in three layers of the eye. It can be visbile as defects in the retinal pigment, misformed the blood vessels or even retina detachment. The abnormalities start at about day thirty of the embrionyc development and can become visible at the age of 8-12 weeks.

Inheritance is simple autosomal recessive.

In the past pups were tested with ophthalmoscopic examination which was repeated yearly as long as the dog was used in a breeding program. DNA tests have simplified this.

Degenerative Myelopathy - DM (SOD1A)

This progressive neurodegenerative disease occurs in a lot of breeds, which suggests that the mutation was present before the different breeds were formed. It's not common in the Border Collie. The cause is a change in a single nucleotide. Symptoms start with weakness in the hind limbs and gradually turns into paralysis. It occurs around the age of eight years. Most dogs are euthanized when the symptoms get worse.

Because it stems from a simple mutation DM is also inherited as a recessive autosomal disease and a DNA test is available.

Goniodysgenesis and glaucoma (BCG)

The disease occurs in several breeds. It was first seen in the 90's in Australia and has spread later to the USA and Europe. It's caused by a mutation of a single nucleotide but the symptoms are not so simple.

The channels which drain excessive fluid from the anterior eye chamber are narrow or blocked. This has to do with malformation of the area where the base of the iris meets the cornea (goniodysgenesis). The pressure inside the eye increases and ultimately the retina is damaged which results in blindness.

It seems that mild forms of glaucoma are not associated with the mutation. In some dogs with severe forms of goniodysgenesis glaucoma is not diagnosed. It seems that goniodysgenesis is essential for glaucoma but there are other factors necessary for the glaucoma to develop.

Dogs which are heterozygous for this mutation may develop glaucoma and goniodysgenesis or may be unaffected. This indicates that other compensating factors play a role and simple recessive autosomal inheritance is not completely certain.


Imerslund-Grasbeck Syndrome (IGS)

Vitamin B12 (cobalamin) is a water soluable vitamin. Dogs (like all higher organisms) are not able to produce this essential vitamin and thus rely on B12 from their food. Cobalamin is important in cell multiplication and for the activity of the nervous system.

IGS causes a malfunction in the absorption of B12 in the intestines. Two proteins — CUBN and AMN — form a complex that transports B12 through the cell membrane. In Border Collies a mutation in the CUBN-protein was identified that causes a premature end in the formation of this protein. It is rendered non-functional because of this change.

Pups of 6–12 weeks of age fail to thrive and show a loss of appetite. Their blood and bone marrow show some specific changes.

Research among 203 European Border Collies by Owczarek et al. (2013) showed 6% carriers. Inheritance in recessive autosomal.

Malignant Hyperthermia (MH)

Affected animals show increased body temperature in response to anaesthesia. The syndrome is seen in many species, including humans.

The single nucleotide mutation occurs in a protein that plays a role in the regulation of calcium levels. The mutated protein responds to the trigger molecules by releasing calcium ions. As a result muscles contract, O2 levels drop, CO2 levels rise and a lot of heat is generated. If not treated properly it can even be fatal.

Inheritance is dominant autosomal. As some dogs may never come in contact with the trigger substances affected dogs may never show the symptoms.

Multidrug Resistence (MDR1)

Several mutations are known in the Border Collie that affect a protein that plays a role in the transportation of certain drugs. It influences both the blood-brain barrier and the excretion of drugs into bile and urine. Affected animals are very sensitive to certain drugs because the drugs can enter the brain more easily and excretion is inhibited (resulting in high blood levels).

Heterozygotes can have problems with this protein (although less severe). Several breeds are affected, primarily the herding breeds. It is believed that the main MDR1 mutation comes from a single dog from Great Britain at a time when the breeds in the UK were not yet isolated. In some breeds the gene frequency of the mutation can be up to 70%. In the Border Collie it is luckily less than 5%. Several years ago a quick round among several laboratories learned that at that time they didn't have any positive tests for affected Border Collies.

Affected dogs can be treated with alternate drugs or lower doses.

Neuronal ceroid lipofuscinosis (NCL)

NCL occurs in many species (including humans) and many mutations are known among different animals. In Border Collies a mutation of a single nucleotide in the gene CLN5 causes this disease.

The gene causes an accumulation of lipopigments (ceroid and lipofuscin) in the lysosomes inside cells. Around the age of 15 months the first neurodegenerative symptoms are seen. Symptoms include psychical changes, ataxy, restlessness, aggression, hallucinations, hyperactivity and also epileptiform attacks. Degeneration happens quite fast and most dogs won't get older than approximately two years.

The mutation is quite rare (around 3.5%) and is inherited autosomally recessively.

Dental Hypomineralization (Raine Syndrome)

A mutation of a single nucleotide in the gene that encodes a protein (FAM20C) which is involved in the mineralization of teeth and bones is the cause of this disease. Symptoms include extensive wear of teeth, brown teeth and pulpitis. Raine-syndrome only occurs in Border Collies and is relatively common. Hytönen et al. estimate that around 11% are carriers. Inheritance is recessive autosomal.

Sensory Neuropathy (SN)

A mutation in the FAM134B-gene which encodes for a protein that plays a role in the long time survival of neurons causes a severe neurologic disease. Symptoms start early in the life of a dog (2–7 months of age) and start with loss of coordination and proprioception, and later also loss of the sensation of pain. The hind limbs are more affected and most dogs are euthanized because of the symptoms.

SN is autosomal recessive inherited.

Trapped Neutrophil Syndrome (TNS)

A deletion of four nucleotides in gene VPS13B make a protein disfunctional that is important in the functioning of a type of white blood cell, the neutrophil. As a result these white blood cells are formed normally inside the bone marrow, but fail to be released to the blood stream and tissues. Without these white blood cells it's impossible to fight infections. The first symptoms can be seen in pups of two weeks old and most affected dogs die early (or are euthanized) because of infections within the first four months of their lives.

Inheritance is recessive autosomal. Shearman, Wilton 2011 found that the mutation in a single dog from Australia spread to all affected Border Collies. The mutation had a frequency of approximately 6.4%.

Owczarek-Lipska M, Jagannathan V, Drögemüller C, Lutz S, Glanemann B, Leeb T, et al. (2013) A Frameshift Mutation in the Cubilin Gene (CUBN) in Border Collies with Imerslund-Gräsbeck Syndrome (Selective Cobalamin Malabsorption). PLoS ONE 8(4): e61144. https://doi.org/10.1371/journal.pone.0061144

Hytönen MK, Arumilli M, Lappalainen AK, et al. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes. PLoS Genet. 2016;12(5):e1006037. Published 2016 May 17. https://doi.org/10.1371/journal.pgen.1006037

Shearman, J.R. & Wilton, A.N. BMC Genomics (2011) 12: 258. https://doi.org/10.1186/1471-2164-12-258

Bossennec M., Di Roio A., Caux C. & Ménétrier-Caux C. (2018) MDR1 in immunity: friend or foe?, OncoImmunology, 7:12, DOI: 10.1080/2162402X.2018.1499388