Module 2.1: Health – Copper Storage Disease

A Practical Genetic Guide for Breeders

Copper Storage Disease (historically called copper toxicosis) has shaped modern Bedlington breeding more than any other single health issue. Over the past fifty years, our understanding has evolved from simple inheritance assumptions to a far more nuanced view involving multiple genes and modifying factors.

For today’s breeder, the goal is not simply to “test and eliminate,” but to understand, interpret, and manage responsibly. This guide walks through that evolution in a clear, practical way.

Foundations: How Genetics Works in the Dog

Every Bedlington puppy is built from DNA packaged into chromosomes.

• Dogs have 39 pairs of chromosomes (78 total).
• One chromosome of each pair comes from the sire.
• One comes from the dam.
• Eggs and sperm contain only 39 chromosomes (one from each pair).
• Fertilization restores the full set.

Because chromosomes assort randomly and exchange segments during formation of eggs and sperm, each puppy is genetically unique.

Key Genetic Terms

Understanding these basics makes Copper Storage Disease easier to interpret.

The Early Model: Simple Recessive Inheritance

Copper Storage Disease was originally believed to be caused by a single autosomal recessive gene.

Using standard notation:

• C = normal allele
• c = defective allele

Possible Genotypes

Carrier × Carrier Breeding (Cc × Cc)

Expected ratio over many puppies:

• 25% Clear
• 50% Carrier
• 25% Affected
• Phenotypic ratio ≈ 3 normal : 1 affected

However, in small litters, ratios vary widely due to chance.

This model guided breeding decisions for decades.

And in some cases, continues today.

The Biopsy Era: The First Reliable Tool

Research led by Mike Herrtage (University of Cambridge) established that:

• Blood tests were unreliable in subclinical dogs.
• Clinical illness often appears after age two.
• Liver biopsy (after 6 months of age) was the only definitive method of identifying affected dogs.

Biopsy allowed breeders to:

✔ Identify affected dogs before clinical disease
✔ Remove them from breeding programs

But biopsy could not distinguish:

• Clear (CC) from Carrier (Cc)

Test matings were used, but certainty was never absolute.

Breeders needed a DNA-based solution.

The Linked Marker Period (C04107)

In the mid-1990s, a DNA “linked marker” test (C04107) was introduced.

A linked marker:

• Is near a gene but not inside it.
• Tracks with the mutation most of the time.
• Is not the mutation itself.

Markers were labeled:

• “1”
• “2”

Originally:

• Most affected dogs were 2:2
• 1:1 were thought clear
• 1:2 were thought carriers

Over time, contradictions appeared:

• 1:1 dogs biopsied affected
• 1:2 dogs biopsied affected
• 2:2 dogs biopsied normal

The linkage was imperfect.

The search continued.

The Breakthrough: COMMD1 Deletion

Researchers at:

• Animal Health Trust
• University of Nottingham
• Utrecht University
• University of Alberta

identified a large deletion in the COMMD1 gene.

A direct DNA test was developed.

COMMD1 Test Categories

This was a major advancement.

For a time, it appeared definitive.

The Complication: More Than One Gene

As more dogs were tested and biopsied, inconsistencies appeared:

• Some dogs without COMMD1 deletions were biopsy affected.
• Some dogs with deletions showed milder disease.
• Some lines demonstrated wide variability in copper accumulation.

Conclusion:

COMMD1 deletion is a major factor — but not the only contributor.

This shifted the model from simple Mendelian inheritance to genetic complexity.

The Emerging Role of ATP7B

More recent research has identified a variant in the ATP7B gene (c.4358G>A) associated with copper accumulation in some Bedlington Terriers.

ATP7B plays a role in copper transport within liver cells.

Testing is available through:

• Orthopedic Foundation for Animals
• Veterinary Genetics Laboratory
• Embark Veterinary

Interpretation is still evolving.

Current Genetic Understanding

Copper Storage Disease in Bedlingtons is likely:

• Polygenic
• Influenced by modifiers
• Variable in expression

Why Phenotype Does Not Always Match Genotype

Genotype ≠ guaranteed outcome.

Factors influencing copper accumulation:

• Dietary copper levels
• Chelation therapy
• Age
• Liver resilience
• Additional modifying genes

Some dogs tolerate high copper levels.
Others develop liver failure with less accumulation.

This variability strongly suggests multi-gene involvement.

Modern Testing Strategy

Today’s responsible breeder uses layered information.

Recommended Testing Approach

✔ Test all breeding dogs for COMMD1 deletion
✔ Consider ATP7B variant testing
✔ Monitor liver enzymes when appropriate
✔ Use pedigree knowledge
✔ Avoid affected × affected breedings

What to Avoid

✘ Eliminating all carriers immediately (risking gene pool contraction)
✘ Relying on a single test result
✘ Ignoring family history
✘ Assuming “clear” means zero genetic risk

Strategic Breeding Considerations

In a numerically small breed like the Bedlington Terrier, health management must balance:

• Disease reduction
• Genetic diversity
• Structural integrity
• Temperament stability

Eliminating every carrier too rapidly can:

• Increase inbreeding
• Reduce diversity
• Amplify other recessive diseases

Strategic breeding means:

• Using carriers to clears thoughtfully
• Replacing carriers with clears over generations
• Monitoring copper trends in lines

Progress, not panic.

Practical Breeding Scenarios

Scenario 1: Carrier × Clear (COMMD1)

Expected:

• 50% clear
• 50% carrier
• 0% affected

This can be a responsible choice if:

• Genetic diversity is preserved
• Carriers are replaced with tested clear offspring

Scenario 2: Clear (COMMD1) but ATP7B Variant Present

Requires:

• Cautious interpretation
• Possibly pairing with low-risk mate
• Clinical monitoring

Scenario 3: Biopsy Affected but No COMMD1 Deletion

Indicates:

• Other genetic contributors involved
• Need for broader genetic interpretation

Today

Copper Storage Disease in the Bedlington Terrier has moved through three major phases:

1. Simple recessive assumption
2. Linked marker testing
3. COMMD1 deletion discovery
4. Recognition of additional genetic contributors (ATP7B and others)

We are now in a refinement phase.

The future will likely include:

• Expanded multi-gene panels
• Better risk stratification
• More precise breeding guidance

The Breeder’s Role: Stewardship

Copper Storage Disease is not just about eliminating a mutation.
It is about managing a population responsibly.

The wise breeder:

• Tests thoughtfully
• Interprets cautiously
• Maintains diversity
• Studies pedigrees
• Tracks outcomes over time

Genetics is not static.
Our understanding evolves.

Professional breeding demands that we evolve with it — carefully, scientifically, and without overreaction.

That is how we protect the future of the Bedlington Terrier.

References

• Herrtage, M.E., University of Cambridge – Early biopsy research
• van de Sluis, B. et al., Utrecht University – COMMD1 deletion identification
• Cox, D.W., University of Alberta – Evaluation of COMMD1 causality
• Animal Health Trust & University of Nottingham – DNA test development
• Orthopedic Foundation for Animals – Copper Storage Disease testing guidelines
• Veterinary Genetics Laboratory (UC Davis) – ATP7B variant data
• Embark Veterinary – Copper-related genetic panel information