Genetic Testing for PLN-Associated Variant Genes

After years of research supported by hundreds of Wheatens and their owners and breeders, Dr. Meryl Littman and Dr. Paula Henthorn at the University of Pennsylvania School of Veterinary Medicine (Penn Vet) identified mutations associated with PLN in two genes.

This project has implications throughout the Wheaten world, and any owner or breeder can participate in this Research.

For the PLN-Variant Genes Test it is preferred that Penn Laboratory (PennGen) is used as this enables continuity of research. In Europe and Scandinavia Laboklin Laboratories also offer the test but the result does not directly aid this research.

It is important when testing for the PLN-Variant gene that this includes both NPHS1 and KIRREL2 genes in the test.

Testing for variant alleles associated with a risk for PLN (‘DNA test’) was initially developed at Penn based on Drs. Littman and Henthorn’s research. That research showed that a DNA variant occurred in each of two genes, NPHS1 and KIRREL2. These genes are positioned next to each other on dog chromosome 1. The presence of these two variants on both copies of chromosome 1 indicated significantly increased risk for developing PLN (Protein Losing Nephropathy). In all Wheatens examined in the research study, these genes always showed the same patterns:

  • All dogs that were 1-1 for NPHS1 were also 1-1 for KIRREL2 (both copies each gene normal)
  • All dogs that were 1-2 for NPHS1 were also 1-2 for KIRREL2 (heterozygous for both genes)
  • All dogs that were 2-2 for NPHS1 were also 2-2 for KIRREL2 (both copies of each gene are variant)

In other words, the normal versions of these two genes were always inherited together, and the variant versions to these genes were always inherited together. Because of this, it is not known with 100% certainty which gene variant puts a dog at high risk for developing PLN, or whether or not they both act together (although, based on what is known about those two genes and proteins they encode, it is thought that NPHS1 is more likely).

Among the well over 4,000 Soft Coated Wheaten Terrier samples that Penn has analyzed since the test was introduced in 2012, there have been three (3) Wheaten Terriers with results in which both genes had different genotypes (for example 1-1 for NPHS1 and 1-2 for KIRREL2). In these cases, Penn reports the results more specifically, and discusses the ramifications of these results with the dog’s owner.

Penn’s DNA testing continues to test both genes for two reasons. It is not 100% certain which of the two gene variants is most important in the PLN disease process. Running two tests for each sample increases the quality control in the testing process. The websites of some commercial labs indicate that they only test for one of the genes, usually NPHS1.

PennGen Laboratories, at the University of Pennsylvania School of Veterinary Medicine are, from April 2020, offering genetic testing for PLN (and Microphthalmia and Degenerative Myelopathy) in Soft Coated Wheaten Terriers. Select this link for further details of costs. (pdf - opens on new page)

A simple cheek swab test (two swabs for each dog) is used to determine an individual dog’s DNA status. Litters can also be tested, as can frozen Semen.

Information guides and how to obtain swabs, The SCWT Club of America.

In the UK, information can be obtained by email from the Health Team of the SCWT Club of GB.

Test Results definitions (updated August 2017)

This table clarifies the reporting formats between PennGen and Laboklin test results.

Genetic Term Definition What does this mean? Other Common Terms Results from Penn Results from Laboklin

Homozygous Negative

A dog without any of the variant alleles

A dog that has no copies of the variant alleles is at the least risk of developing PLN

0

0/0

No copies

'Normal'

'Clear'

Homozygous

1/1

N/N (Clear)

Heterozygote

A dog with one copy of the variant alleles

A dog with one copy of the variant allele is at medium risk of developing PLN

1

0/1

'Carrier'

1 Copy

Heterozygous

1/2

N/PLN (Carrier)

Homozygous Positive

A dog with two copies of the variant alleles

A dog with two copies of the variant alleles is at the highest risk of developing PLN, but this does not mean it will develop PLN

2

Both copies

Homozygous for the PLN causative mutation

2/2

PLN/PLN (Affected)

Affected refers to both copies of the allele,

it does not mean the dog is currently, or will be affected with PLN

Please use the PennGen website at: http://tinyurl.com/3mn6ykv to establish Your Account

Submitting Test Swabs

It is VERY IMPORTANT that you follow the instructions guides on The SCWT Club of America's web page and that the two swabs and documents submitted for each dog are clearly identifiable with details for both owner and dog.

Remember to include credit card details on the submission form. Take copies of the documents you send for future reference.

A few points specific for UK participants:

1. Two swabs, associated paperwork and suitable 'bubble wrap' is about 50 gms and can be sent at letter rate.

2. Customs - items sent at 'Letter Rate' do not need a Customs Declaration, otherwise state: 'plastic brushes and stationery'

3. A four generation pedigree can be provided by WHI (via e-mail) if one is not available.

4. The Guidance notes suggest avoidance of weekend receipt of samples in the USA, but please note this refers only to blood samples that are sent and does not apply to swab tests.

5. The Guidance notes also refer to a Ziploc bag. To avoid confusion this is a clear plastic re-usable/re-sealable bag, generally used for sandwiches or fridge/freezer storage.

Test outcomes

You will be contacted direct with your dog's result. This is confidential between you and the Researchers.

Please remember that the genetic status of both sire and dam will influence their offspring.

Carefully read 'UNDERSTANDING BREEDING COMBINATIONS - A Breeders' Tool' an update January 2014), click here for pdf.

Queries

If you have any questions contact the SCWTCA liaison Pam Mandeville at bannerscwt@yahoo.com

Thank you for your participation.


What is PLN?

Further reading about PLN can be found on our pages about hereditary diseases.

1. primary information

2. comparisons with other hereditary diseases

3. help with diagnosis


Wheaten Health Initiative make a donation to PLN research

The WHI Genetic Research Fund is held with the object of providing assistance to research organisations involved in this important area of work. The Steering Group of WHI agreed that the PLN research project initiated by Drs Littman and Henthorn, should receive some of the money from this Fund.

On 15 May 2012, a donation of £532.90, just over $800 USD, was transacted through the aid of SCWTCA Endowment Inc., to Drs Meryl Littman and Paula Henthorn, of the University of Pennsylvania School of Veterinary Medicine in support of their recent research: Genetic Testing for PLN-Associated Variant Genes.

Read Dr Littman's reply.