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2026 Health Seminar -  Genetic Testing
with Kari Ekenstedt
April 24, 2026
About Me
Brown white Tibbie
DNA is Amazing!

DNA makes up who you are! 

  • What makes you human, what makes your dog a dog, and part of what makes all of us a little different

DNA is an incredible way to store information – one we’ve not been able to replicate artificially

  • Average mammalian genome is about 2.5-3 billion base pairs (2.5-3 Gb)

  • Average mammalian genome codes for 20,000 genes

Genes Typically Come in Pairs

This is because normal mammals (and some plants) have two sets of chromosomes.

  • Normally, every chromosome has a pair

  • Typically, each gene has two copies

Is That Disease/Trait/Condition Inherited or Not?

This can be tricky.
Example: Cataracts

  • Several forms of hereditary cataracts exist

  • But cataracts can also occur from injury, toxin, or disease (like diabetes)

 

Things to consider:

  • Age the disorder becomes evident

  • Whether or not littermates or other relatives are affected

  • Is it known to occur in the breed?

Human karyotype
Single Gene Disease

  • A mutation (or variation, or a change) in just one gene can result in disease

  • Hundreds have been described and solved in dogs

  • Ditto for people

 

Mutations (changes) occur every single generation as eggs and

sperm are produced

  • Usually neutral, sometimes good, sometimes bad

  • This is not anybody’s fault – natural process

    • Our cellular machinery just occasionally makes istakes when copying!

Recessive Trait/Disease

 Autosomal recessive inherited diseases are the most common type of single-gene disorders in dogs

Usually from inbreeding

  • (Note: we would not have purebred dogs without SOME inbreeding – so care has to be taken with inbreeding!)

  • In this scenario, an affected dog must inherit two copies of the mutant allele, one from each parent, to have the disorder/altered phenotype

  • “Allele” = Version of a gene

 

Dog with one copy (“carrier”) or with two copies of the normal allele will have the normal trait (no disease)

 As long as the frequency of the mutant allele for a disorder is low, it can lurk in a breed for many generations...
…Only to appear when two carriers are mated (by chance) and affected individuals are observed in a litter. Sometimes this is multiple generations away from where the mutation first occurred.

 

Frequency of the mutant allele can become very high in these scenarios

  • Popular sire effect

 

Hard to eradicate without a genetic test

  • Carriers are clinically normal

Dominant Trait/Disease

Here, only one copy of the mutant allele is required to show the trait or disease
These are much rarer compared to recessive
Examples:

  • Black Mask

  • Cataract

NOT Single-Gene Disease…
four tibbies_edited.jpg

Many genetic diseases and conditions are NOT single- gene! 

  • Dogs: hip dysplasia, cranial cruciate ruptures, idiopathic epilepsies

  • Called “polygenic” or “complex” disease

 

Multiple – sometimes hundreds – of genetic loci can contribute to a disease (or trait)

  • Dog that likes water/swimming!

The Million Dog Paper (2023)

  • 250 total single-gene tests

  • 39 Tibetan Spaniels tested

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010651#sec021

PRA (Progressive Retinal Atrophy) Type 3

In the “Million Dog” paper: of 39 Tibbies tested, one was heterozygous (allele frequency: 1.35%) for PRA Type 3
 

Sample size is small, so the true (current) breed frequency isn’t fully defined

​

Original paper published in 2014: 14.7% carriers and 85.3% homozygous wild type (clear)

  • Breed frequency likely changing over time….hopefully decreasing slowly as people select away from it 

PRA Type III, FAM161A-related

Loss of vision due to death of cells in the retina (back of the eye) – can be rods or cones or both

Leads to vision loss and eventually blindness 

 

Clinical Picture in Tibbies

  • Clinically indistinguishable from other forms of PRA

  • Age at diagnosis is relatively late (~5 years of age), but broad, and could actually be younger

​

FAM161A gene has a mutation

  • (Large insertion near exon 5 splice site)

  • Autosomal recessive, fully penetrant

    • Breeding considerations

      • Consider individual health (puppies you are creating)

      • Consider breed health (the breed as a whole)

Laboratories
Autosomal Recessive: Breeding Recommendations

The “E” allele is recessive, and represents the mutated version of FAM161A. 


The “N” allele is the dominant allele, and represents the normal, fully functional version of FAM161A.  Hypothetical offspring are in the middle four boxes

Take-Home Message with Hypothetical Matings

  • All potential matings are shown for a single-gene, recessive condition like PRA Type 3

  • Do not do any of the crosses that produce red puppies (they will become blind)

    •  This is considering individual dog health

  •  It is OKAY to do matings that make purple (carrier) puppies, because those puppies are not affected and we want to preserve as much of the genetic diversity of the breed as possible. 

  • So, it is OKAY to use carriers in matings, as long as you’re breeding to a clear.

​

Always retain the best, and eventually the best will also be clear for PRA Type 3

If you immediately remove all carriers from the breed, you’ll toss out a lot of other good genetics that should be retained

This is considering population health of the whole breed

​

Other things to note: 

  • The IDENTICAL FAM161A mutation is present in the Tibetan Terriers (It was not found in Lhasa Apsos)

  • In both Tibetan Spaniels and Tibetan Terriers PRA Type III, FAM161A-related is probably not the only form of PRA (Heterogeneity exists – not all cases were explained by this mutation)

  • English Shepherds have PRA from a DIFFERENT mutation in the same FAM161A gene

    • Genetic testing for the English Shepherd FAM161A variant is not useful in the Tibbies

CDDY - IVDD
From the "Million Dog" paper

  • CDDY-IVDD

  • Not the same as CDPA

Chondrodysplasia (CDPA)

CDPA = “breed-defining chondrodysplasia”

  • FGF4 on CFA18 (retrogene insertion)

  • Shortened long bones in the legs

  • Early closure of growth plates

  • No known negative health effects

  • Co-dominant (one copy = milder change, two copies = more extreme change)


Tibetan Spaniel DOES have this mutation

Tibbie in snow
CDDY (also called: CDDY-IVDD)

  • CDDY: Chondrodystrophy

  • IVDD: Intervertebral Disc Disease

  • CDDY with IVDD risk is also from an FGF4 retrogene insertion, but on CFA12

    • Also co-dominant (one copy = milder limb shortening; two copies = more dramatic limb shortening)

    • Effects on the limbs are milder than CDPA

    • Having the CDDY variant creates some increase to head width

    • ALSO has effects on the discs in the spine

 

Because CDDY is DOMINANT then having just one copy of CDDY means the dog’s discs are not normal (note that this is different than in recessive diseases)

Intervertebral Discs

Just like in humans, discs are cushions between the bones (vertebrae) of the spine

Disc disease in dogs can be broken into two groups:
 

  • Hansen’s Type 1: younger dogs, typically dogs with shorter legs; bony calcification of the discs and multiple affected discs

  • Hansen’s Type 2: older dogs, larger breeds, typically just 1-2 discs affected

Spine

The CDDY mutation is present in most of the dogs with Hansen’s Type 1 IVDD
 

  • Degeneration and calcification of the disc (IVDD)

  • Predisposes the dog to herniation of the disc

    • ​Painful, can be life threatening

    • The disc (or part of the disc) bulges into or presses into the spinal cord, compressing it

    • What signs the dog shows will depend on what level of the spine the disc herniates at and how much the spinal cord is compressed.

    • Surgery can decompress the spinal cord, medical management sometimes used (case-by-case basis)

    • Screening x-rays can sometimes see narrowed disc spaces and/or calcification of the discs

​

  • With either one or two copies of the CDDY mutation, the dog is more likely to experience premature degeneration and calcification of the intervertebral disc

  • ​Co-Dominant mode of inheritance

  • High risk of herniation

    • ​BUT…herniation is not guaranteed (although the discs are not normal) because environment can influence, too

    • Discs can also herniate away from the spinal cord – and these dogs might not have signs at all

​​

Signs of disc herniation (into spinal cord)

  • Back pain: stiffness, arched back, shaking/shivering, muscle spasms, hesitation to move, vocalization when touched

  • Lameness, limb weakness, knuckling of the paws when walking, incoordination when walking, or paralysis

  • Can also see fecal and/or urinary incontinence

Tibbies and CDDY

  • In the million dog paper, 39 Tibbies were tested (78 copies) (~12% allele frequency)

    • 9 copies were “alternate” (the mutated version)

  • Wisdom Panel data (publicly available, separate data set): 100-500 dogs tested, 8% allele frequency

Recommendations

Keep body weight lean and keep muscles healthy (uphill walks, swimming)

  • Avoid high-impact movements that twist or compress the spine

  • Ramps for older dogs to get up into car, onto couch/bed, etc.

 

Keep nails short!

​

Breed screening via radiograph? No published research on what the clinical picture looks like in Tibbies specifically
Breed away from CDDY? Yes, but SLOWLY!

  • Favor one-copy at-risk dogs (over two-copy at-risk dogs)

  • Probably best to avoid breeding dogs with many calcified discs on x-ray

Tibbie meeting a cat
Tibbie with a cat
Degenerative Myelopathy (DM)

  • In the Million Dog paper, 39 Tibbies tested had an 11.5% allele frequency of the SOD1 mutation

    • This mutation has ONLY been validated in breeds like the Corgi and German Shepherd

    • DM can only be diagnosed at postmortem exam (by looking at the spinal cord under a microscope)​

  • Tibetan Spaniels not affected with DM as far as I can find in the scientific literature…

    • …so this test is irrelevant in the breed

Familial Dilated Cardiomyopathy and Sudden Cardiac Death
Tibbie on a statue

  • Missense variant published in 2019 in the Doberman Pinscher

    • ​In the Million Dog paper, one Tibbie was a carrier for this mutation

    • It is autosomal dominant, but has incomplete penetrance

    • This variant has NOT been validated in the Tibbie breed

 

  • So we truly do not know if it means anything in this breed

  • If anyone has a Tibbie with this variant that does die suddenly from cardiac death – let me or another dog genetic researcher know about it!

What to do if something comes up?

An example in another breed: Basset Hounds
 

  • Two littermates died ~6 months apart

  • Died unexpectedly between 3-4 years of age

    • ​Necropsies performed and the pathologist diagnosed a glycogen storage disease

    • These are usually genetic, so the pathologist contacted me

  • Tibetan Spaniels not affected with DM as far as I can find in the scientific literature…

    • …so this test is irrelevant in the breed

Basset
Summary of What We Did with the Basset Hounds

  • We whole genome sequenced the two affected dogs 
    and their unaffected sire

  • We identified the causative mutation

    • It is an autosomal recessive, single-gene disease

  • We developed a genetic test and offered it to the public

  • This all happened so quickly that the national breed 
    club didn’t even know it was an issue yet in the breed

    • We caught it before it spread widely

    • This saved untold numbers of dogs from dying and the heartache it would have caused to the breeders and owners

  • This is a best case scenario success story, and took breeders, researchers, and clinicians all coordinating together

Tibbie in scale.jpg
Breeder Role

Round-up samples

  • Contact puppy owners

  • Encourage submission

  • Cases and controls (affected and unaffected) are needed

Funding options?

  • Ostrich behavior will probably be worse in the long run

  • Patience

    • Projects don’t always work out immediately, or ever

    • The disease may not be single-gene

Note that we NEVER breach confidentiality – your name, your dogs’ names, your kennel name, etc., will NEVER be shared or published in any way

What's Next?

  • If researchers are very, very sure they have the causative mutation identified

    • Offer test OR license test to commercial company

    • Possibly present the work at a scientific conference

    • Speak at appropriate National Specialty to share with breeders!

  • Publish paper – this is the scientific review

    • After that…the test will likely be picked up by many commercial testing companies

Summary

  • Single-gene diseases are the “lowhanging” fruit

    • Complex/polygenic diseases are a lot harder

  • New ones are going to keep popping up

    • Because of dog breed structure and because our genomes change every generation

  • The science is a fascinating process, but it cannot be done without teamwork and the help of breeders

Monitoring Breed Health

Breed health databases are VITAL for tracking health information in a breed

  • Use the Tibetan Spaniel Health Net

 

  • Helps identify problems, trends, and can catch new diseases as they pop up (because they will)

    • For example: Which cancers are most prevalent?

  • Other health screening is also super important

    • Elbows, Hips, CAER (formerly called CERF) exams, patellas, etc.

Questions?

  • Contact Information:  Kari Ekenstedt

Email:  kje0003@purdue.edu​

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