OptiGen FN Test for Familial Nephropathy

The Optigen FN Test for Familial Nephropathy

Important Announcement Regarding an Open FN Registry - please scroll to bottom of this page.

For detailed information about FN disease, along with further suggested readings, please link to the health related articles on the ECSCA website at www.ecsca.info. Highlights of that information are summarized here.

Background:

The OptiGen FN test is a DNA-based test that accurately diagnoses a fatal kidney disease that occurs in English Cocker Spaniels (ECS). The test also detects CARRIERS of this disease and clears dogs that are genetically NORMAL.

Familial Nephropathy (FN) has been referred to in several ways: kidney failure, fatal renal disease, juvenile nephropathy, renal cortical hypoplasia, hereditary nephritis (HN), Autosomal Hereditary Recessive Nephropathy (AHRN) in canines and Alport's Syndrome in humans. Among ECS breeders in the U.S. , the most common reference is to “FN” and this term is used to name the OptiGen test.

FN is inherited in an autosomal recessive pattern in the ECS. This means the gene mutation responsible for FN is located on an autosome (that is, a chromosome that is not a sex chromosome) and FN disease results when the gene mutation is passed to the offspring by both the mother and the father. (A similar kidney disease in other breeds can be caused by different gene mutations with X-linked or dominant inheritance.)

FN disease is a juvenile-onset fatal kidney (renal) failure recognized in ECS worldwide for more than 50 years. The renal disease caused by FN invariably is progressive and ultimately fatal; however, the rate of disease progression observed in affected dogs is more rapid in some individuals than in others.

Dogs with FN typically develop chronic renal failure between 6 months and 2 years of age, with eventual and sometimes rapid destruction of both kidneys. The early clinical signs are the same as those associated with chronic renal failure due to any other cause. These include excessive water consumption, excessive urine volume, reduced growth rate or weight loss, poor quality hair coat, reduced appetite, and vomiting. Persistent high levels of protein in the urine of a young ECS most often proves to be due to FN.

Genetic Testing:

Early in the disease course, a diagnosis can be difficult. Definitive clinical diagnosis can require examination of kidney tissue after death. The FN genetic test solves this problem immediately since presence of the FN gene mutation is accomplished by testing a DNA sample. This result gives the owner immediate diagnostic information and aides in making decisions for the affected dog and for breeding strategies.

Because the OptiGen FN test is a mutation-based gene test, it accurately and specifically identifies normal dogs, carriers (heterozygous dogs) and affecteds. Possible test results are listed in the table below.

Possible results using the OptiGen FN test
N =	Normal(Clear)	Homozygous for normal gene, so will never develop the disease
C =	Carrier	Carries one disease gene, but will never develop the disease
A =	Affected	Homozygous for disease gene and will develop the disease

The OptiGen FN test can be done reliably at any age – even in young pups, and the result will be the same at any age, and will be the same whenever it is repeated.
The exact frequency of this disease, and of the gene mutation causing it, are not known as yet. Data accumulated through genetic testing will help to provide that information.
Tallies of test results are updated and provided quarterly to national breed clubs.

Breeding Strategies using the FN Test:

This table highlights all the desirable breedings that include at least one Normal/Clear parent. All other breedings are at high risk of producing Affected pups. However, all Normal and Carrier dogs can be bred safely. It isn't necessary - or even desirable - to remove clinically healthy dogs from the breeding population. But when choosing pups to retain as potential future breeding stock, it is important to select for Normal/Clear dogs and select against Carrier dogs.

Expected results for breeding strategies using the OptiGen FN test
Parent 1 Status	Parent 2 Status
Parent 1 Status	Normal/Clear	Carrier	Affected
Normal/Clear	All = Normal/Clear	1/2 = Normal/Clear 1/2 = Carrier	All = Carrier
Carrier	1/2 = Normal/Clear 1/2 = Carrier	1/4 = Normal/Clear 1/2 = Carrier 1/4 = Affected	1/2 = Carrier 1/2 = Affected
Affected	All = Carrier	1/2 = Carrier 1/2 = Affected	All = Affected

Benefits & Limits to All Genetic Testing:

The benefits of genetic disease testing are clear. With informed breeding practices, breeders immediately can avoid producing FN affected pups, yet use any healthy dog in their program regardless of Normal or Carrier genetic status. And since genetic testing can be done at any age, each dog’s genetic status can be known before clinical disease signs are recognized. Over several generations of selection away from the disease gene, breeders can even eliminate a disease gene completely from their line.

BUT, there are basic limits for any and all DNA genetic tests. Whether a test is mutation-based or marker-based, it identifies only the specific mutation being tested or the association between a specific marker set and the disease. For example, a mutation test detects one specific mutation in one specific gene. If there are several different mutations or several different genes that can cause the same condition, one must discover and then test for each mutation and each gene. It can be difficult or even impossible to know how many mutations or how many marker sets exist in all the members of a specific breed. As more and more dogs are tested, previously unknown variations may come to light.

Ordering the FN Testing:

The FN test is done on a small sample of blood obtained by your veterinarian. This allows the lowest risk of contamination of the sample and added assurance of a match of the sample with the identified dog. Please read the paragraphs below, and then read “Instructions and Information” to learn about ordering a test, shipping a sample, and prices.

I. Dogs already tested for OptiGen prcd-PRA from any country:

OptiGen’s FN license allows us to test FN in samples that we have already received as of December 8, 2006, from any country worldwide. OptiGen has retained frozen samples from all ECS prcd-PRA tests done previously, and we've decided to make these available for FN testing, even if the owner did not pay the fee for long-term storage. We hope this will help many obtain the new FN test more easily. You may order the FN test online on a stored sample. Link to "Order Test" and complete the order form as usual. Be sure to indicate that this dog's sample already is at OptiGen by selecting "Blood sample is already at OptiGen under a long-term storage agreement." Mark this choice even if you did not specifically pay for Long-Term Storage.

Blood Sample Information:

Blood sample is already at OptiGen under a long-term storage agreement.

Blood sample will be submitted with this request

II. Dogs not tested earlier from U.S., Canada, and all locations EXCEPT Europe, Australia, New Zealand, Japan and China :

OptiGen has exclusive license to provide the FN test in the U.S. and Canada, and non-exclusive right to provide the FN test in all other locations except for new samples from Europe, Australia, New Zealand, Japan and China. When you submit a new blood sample to OptiGen from the included locations, you may choose to order both the FN and prcd-PRA tests on this same sample. The OptiGen full price for the FN test is US$95.00, for prcd-PRA is US$195, with the usual discounts for online ordering and 20/20 Clinics.

For owners in Australia , New Zealand , Japan ,

China

: www.geneticscienceservices.com

For owners in Europe : www.antagene.com

Registries:

Breed clubs may sponsor genetic disease registries and OptiGen may provide some test information directly to the registry in accordance with the club’s official policies. Please go to your club to learn more about this.

Important Announcement Regarding an Open FN Registry:

The FN test is now available from Optigen. At the January 5, 2007 ECSCA Board of Directors meeting, it was voted unanimously to disclose all FN test result information to the ECSCA for ECS dogs in the U.S. This decision was announced at the ECSCA general meeting on January 6, 2007 and will be reflected in the Board minutes published in the next newsletter. Optigen has agreed to facilitate this Open FN Registry, with no added fee for the service, by providing ECSCA with reports on a quarterly schedule.

Anyone who placed their order with Optigen before January 29, 2007 will be sent a consent form by Optigen asking if they would like to disclose their test results and comply with the Open FN registry. For those who have already submitted orders and who do not want this information made public to the ECSCA, their information will not be provided to the ECSCA.

Effective January 29, 2007 all FN orders submitted for U.S. dogs will have the full results of the FN test with details on the dog’s name, AKC number, etc., and owner’s identity sent to ECSCA. This information will be made available to the membership. The manner in which this information will be reported is under consideration at this time.

– Kathy Moore, ECSCA President, Jan 11, 2007

The research leading to this discovery was undertaken by scientists at Texas A&M University . The report on this research is submitted for publication. The technology (patent number 7285388) underlying this test is under exclusive license to OptiGen, LLC for the U.S. and Canada markets from Merlogen, LLC.

OptiGen wishes to congratulate the English Cocker Spaniel Club of America and the Ferguson-Dunelm Memorial Fund for English Cocker Spaniel Kidney Disease Research for their support of this research at Texas A&M University , and to congratulate the many individuals who contributed in various ways to the work underlying this discovery.

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