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linkage faq

Fanconi Test FAQ updated July 27, 2007
On July 14, 2007, the Basenji Health Endowment proudly reported that Dr. Gary Johnson of the University of Missouri released the linked marker DNA test for Fanconi Syndrome in Basenjis. As the first predictive test available for Fanconi Syndrome, we are sure you all have many, many concerns and we’ve compiled this list of Frequently Asked Questions to help. This FAQ is a work in progress, so please check back for updates.

Click to Download the FAQ as a PDF
About the Test
What is a linkage test?
Answer: Linkage is the tendency for genes and other genetic markers to be inherited together because they are in close proximity to each on the same chromosome. A linkage or linked marker test selects a segment (or segments) of DNA at a location on the chromosome and tracks their inheritance. Because DNA segments that lie near each other on a chromosome tend to be inherited together, these markers can be used to track the inheritance pattern of a gene that has not yet been identified but whose approximate location is known.
You can read more about genetic linkage at Wikipedia.

How reliable are the results?
Answer: This is a new test. We can report that all of the double-blind samples used for validation fell into one of the four categories (normal, carrier, affected, indeterminate) and that approximately 75% of the samples that tested affected were already known to be affected and none of the samples that tested normal were known to be affected, or had parents that were known to be affected. About 10% of the samples tested returned an indeterminate result.
A significantly larger data set is required to generate meaningful accuracy rates, if you’d like to learn more, read about Bayesian Inference at Wikipedia.

Is it the same as a marker test?
Answer: Yes, a linkage test uses marker(s) to identify conditions caused by an as yet unidentified defective gene. This is not the same as a direct test which identifies the exact gene responsible for a condition.
Why was the linkage test created?
Answer: To reduce the risk of producing Fanconi afflicted puppies now while research continues on locating the actual gene.
Was my dog used to develop the test?
Answer: At this time, we do not have a final list of animals actually used for test development.
My dog was used to develop the test- do I still have to pay $60?
Answer: No. The 48 dogs that were actually used to develop the linked marker test will receive results at no charge. However, these results will not be available until after the breeding season backlog has been cleared and the research team has the manpower available to cross reference their double-blind samples; and if needed, re-run tests if a sample’s results are unavailable.
Why is the test so expensive?
Answer: The $60.00 per dog fee is essentially a time & materials charge covering the cost of reagents used in the test, sequencer time to run the test, OFA recording fee of results, and administrative time to process requests and log results. For comparison, the commercially available Pyruvate Kinase Deficiency (HA) Test for Basenjis costs from $75.00 to $140.00 depending on the testing facility.
Will the direct test be this expensive?
Answer: We cannot predict the cost of the direct test, but our hope is that it will cost no more than the linkage test.
When to Test
To request the Fanconi Test, your dog must first be registered in the Canine Phenome Project (CPP) and complete the breed questionnaires. Print the DNA Sample Submission Form and the Linked Marker Test Form for each dog you are testing and follow the instructions for sample submission.
Dogs that are know to have- or are suspected of having- Fanconi are encouraged to submit samples for the benefit of further research. Please indicate on the dog’s health survey that they are afflicted prior to submitting samples or test requests. There is no charge for testing or recording of results for these dogs.

I want to order a test, whom do I send the form to?
Answer: If submitting a test request when you already have a sample in the CPP, send your Linked Marker Test Form and payment to:
Liz Hansen
321 Connaway Hall
University of Missouri
Columbia, MO 65211
If you are shipping a blood sample at the same time, send your sample, DNA Sample Submission Form, Linked Marker Test Form and payment to:
Dr. Gary Johnson
Basenji DNA Research
320 Connaway Hall
University of Missouri
Columbia, MO 65221
If you have already sent paperwork to Dr. Johnson instead of Liz, don’t be concerned- they’ll figure it out. Don’t forget, all payments should be in US funds payable to the University of Missouri.
I live overseas, can my dogs be tested?
Answer: Any dog registered with the CPP that has submitted a blood sample can be tested. Instructions for shipping samples from outside the United States to the University of Missouri can be found here. We strongly suggest you contact Liz Hansen in Dr. Johnson’s office prior to starting the process.
I already bred this year, should I test the sire & dam? The puppies?
Answer: While the results won’t change the breeding you’ve already done; they will give you information about the parents. Puppies can be tested as soon as they can safely give at least 3mL of blood.
I have a companion dog, should I test? When?
Answer: We ask that people hold off testing dogs that aren’t being considered for breeding in the 2007-2008 season. You may request a test, but it may be delayed until the backlog is cleared. Watch this website for status reports on the backlog.
I have frozen semen from a deceased dog who has blood stored in the CPP, when can I test?
Answer: If you are planning to use the semen this season, by all means request a test now. Otherwise, it is probably best to wait until you are breeding because the direct test may be available.
I have frozen semen from a deceased dog without blood stored in the CPP, can I test?
Answer: We suggest you wait until you are planning to breed as a the direct test may be available. The University of Missouri can extract DNA from semen; however they require 2 straws and they may not get usable DNA. Download this document for instructions. We strongly suggest you contact Liz Hansen in Dr. Johnson’s office prior to starting the process.
Working with the Results
Result emails come from
Should carriers only be bred to normals?
Answer: Fanconi can result if a carrier is bred to a carrier and if a carrier is bred to an affected; it is advisable that carriers only be bred to dogs that test normal. If your dog’s result is indeterminate its safest to treat it as a carrier when breeding.
You can read about Punnett Squares, used to determine the probability of an offspring having a particular gene, at Wikipedia.

Should I spay/neuter my dog based on the results?
Answer: No.
My dog came back affected, should I just euthanize it now?
Answer: No.
I’ve tested my puppies and some came back affected. What do I do? What do I tell buyers?
Answer: Explain to buyers that the breeding was done prior to the availability of a Fanconi test. The buyers should be educated in providing a healthy environment for their dog which includes avoiding unnecessary stress, a quality diet and plenty of drinking water. Buyers should be introduced to the Fanconi Protocol developed by Dr. Steve Gonto, taught the early signs of Fanconi, how to monitor urine for sugar, and be referred to a Veterinarian with Fanconi experience.
My dog came back indeterminate, what does that mean? Should I re-test?
Answer: Our linkage test uses 3 markers (for a total of 6 alleles) to predict Fanconi status and requires that all 3 be in agreement. An indeterminate result means the 3 markers are not in agreement (view sample results) and therefore cannot predict Fanconi status. This would not change with a re-test. It is our suggestion that people treat indeterminate results as carriers when making breeding decisions and continue routine strip testing of urine.

Current Research

AKC Canine Health Foundation Grant 801-A
Title: Characterization of the Mutation Responsible for Fanconi Syndrome in Basenjis
Researcher: Gary S. Johnson, DVM, PhD
Sponsors: The Basenji Club of America, Inc. & The Basenji Health Endowment, Inc.
Abstract: We have been working to characterize the mutation responsible for Fanconi Syndrome, a serious disease of the kidney, which has been fairly common in Basenjis for many years. The disease is recessive with symptoms seldom showing up until dogs are over 4.5 years old. It is, therefore, very hard for Basenji breeders to avoid the disease by conventional breeding strategies. A DNA test that could identify affected and carrier Basenjis as puppies would provide Basenji breeders with a means of eradicating Fanconi Syndrome by selective breeding. Step one in creating a DNA test is to determine the chromosomal location of the mutation. We have completed the first step and localized to a segment of a specific chromosome that represents less than 2 percent of a dog’s DNA. Because this segment of chromosome still contains over 200 genes, our next step is to further narrow the target region as much as possible. We will then examine selected genes within the narrowed region to find the mutation causing the disease. We will create a DNA assay that detects the mutant allele and validate the assay by testing the over 600 Basenji DNA samples in or collection.

Current Status: in progress.

Research Update:
The first generation linked marker DNA test for Fanconi Syndrome in Basenjis is now ready for production and Dr. Johnson’s lab will begin accepting testing requests Tuesday July 17th. The test is $60.00 US (Payable to the University of Missouri) and includes the recording of results in the OFA public DNA database.

To request a test, you must first enroll the dog in the Canine Phenome Project (CPP) at and complete the questionnaires. Print the DNA Sample Submission Form (if you are submitting a blood sample for the first time) and a Linked Marker Test Form for each dog being tested.

Dr. Johnson’s lab can process approximately 150 samples per week, barring problems. If at all possible, please limit test requests to dogs you are planning to breed this year until the initial rush of testing requests has ebbed. Watch this site for updates on the backlog.

Dr. Johnson continues to work on locating the exact mutation responsible for Fanconi Syndrome with the goal of creating a direct test.

Go to the BHE’s Fanconi Test FAQ for answers any questions you may have.

Dr. Johnson is considering PRA research in basenjis employing S.N.P. (Single Nucleotide Polymorphism) chips donated to his facility. These chips are used to rapidly identify single nucleotide differences in the same fragment of DNA from different sources which, when applied to a full genome scan, usually produces excellent results if the data set is sound and the mode of inheritance is reasonably straightforward.

Dr. Johnson will apply his PRA findings in other breeds using these snip chips to basenjis as time becomes available.

What Makes a Good Research Pedigree?
To start research on any disorder, we need good research pedigrees. Pedigrees refers to a family cluster of dogs. Good research pedigrees include families of 30 or more dogs, meeting the criteria listed below, with at least 1/3 not affected. Each dog submitted helps build up that good pedigree – you don’t need to submit multiple dogs to help get us there. The unaffecteds are as important as the affecteds, as one of the ways this information is analyzed is to compare the DNA of related dogs that have the disorder with those that do not.

Researchers look for:
1. Dogs with a condition that is believed to be inherited (Fanconi, PRA, Hip Dysplasia, IPSID, etc.)
2. First degree relatives of the affected (parents, offspring, full siblings).
3. Any mating partner of the affected whether or not affected themselves to complete the family unit.

health content

Fanconi Syndrome
Fanconi syndrome is a disorder in which the proximal renal tubules of the kidney do not properly reabsorb electrolytes and nutrients back into the body, but instead “spill” them in the urine. Symptoms include excessive drinking (polydipsia), excessive urination (polyuria), and glucose in the urine (glucosuria.) If Fanconi is left untreated, muscle wasting, acidosis, and poor condition will also occur.

Untreated, a Basenji with Fanconi syndrome will generally die from the disorder. If caught early and put on the treatment protocol, affected Basenjis can do well.

The earlier the disease is detected, the less damage is done to tissues and organs. Basenjis with Fanconi syndrome typically “spill” glucose into their urine. It is generally recommended that Basenji owners test their dog’s urine for glucose every month, starting at 28 months. Urine glucose test strips (not blood test strips), such as those used by diabetics, are inexpensive and can be purchased at most pharmacies.

The strip should be placed in the Basenji’s urine stream and then read as specified in the strip instructions. If it is not possible to place the strip in the urine stream, then the owner may need to catch the urine in a clean container. (Some breeders use a pie pan, ladle, or serving spoon.) A positive result (glucose present) suggests the possibility of Fanconi, but is not sufficient for definitive diagnosis. Owners should then go to their vet for further testing, including a blood glucose level.

Strip testing indicates only the presence or absence of glucose in the urine at the time of testing. It does not definitively diagnose Fanconi, and it cannot predict whether or not a dog will later develop Fanconi. A dog that test strips normal now may later develop Fanconi. Additionally, the fact that a dog test strips normal and does not have Fanconi does not mean it cannot produce offspring with Fanconi. Presently, there is no test that indicates whether or not a dog has genes for Fanconi syndrome.

Fanconi typically onsets between four and eight years of age, although onsets as early as three years and as late as ten years have occurred. The mode of inheritance is not clearly understood, but it is generally agreed to be an inherited problem in Basenjis. There presently is no test that indicates whether or not a dog can produce Fanconi.

In 1990 a treatment protocol was developed by Dr. Steve Gonto of Georgia, based on the treatments human Fanconi patients receive. The protocol involves acid neutralization, replacing the lost electrolytes and nutrients with bicarbonate and other supplements in specified doses, to re-establish the body’s acid-base balance and keep electrolytes at appropriate levels. Dr. Gonto was given lifetime membership in the Basenji Club of America in recognition of the importance of his work.

The protocol has been very successful in improving both quality and length of life for Fanconi-affected Basenjis. The disorder can be controlled by the protocol, but it cannot be cured.

Because elevated urine glucose is also found in diabetes, Basenjis with Fanconi are often misdiagnosed with diabetes. Diabetes will show high blood glucose along with urine glucose. In Basenjis, a combination of urine glucose and normal or low blood glucose strongly suggests Fanconi syndrome. Venous blood gas studies can verify an electrolyte imbalance consistent with Fanconi syndrome.

Download the Fanconi Treatment Protocol
Hip Dysplasia
Hip dysplasia is a condition in which the hip socket is badly formed, often leading to lameness and arthritis. It is believed to be polygenic, with multiple genes involved in its expression.

Approximately 3 – 3.5% of Basenji x-rays submitted to the Orthopedic Foundation for Animals (OFA) are dysplastic. The actual rate of hip dysplasia may well be higher, as dogs that are obviously dysplastic may not be submitted by the veterinarian and owner.

Breeding stock should be x-rayed for hip dysplasia. The OFA has a web site that permits downloads and searches of dogs that have passed with a grade of Fair, Good, or Excellent. In addition, the OFA has recently added the option of having results placed in an open health registry, so that Borderline and Dysplastic ratings can be made public. Good and Excellent are the preferred grades for breeding stock, although Fair is not considered dysplastic.

Dogs can be OFA screened for hip dysplasia at 2 years of age or older. Screening tests, studying and considering the hip scores of progeny, and breeding from tested stock are the recommended methods of controlling hip dysplasia.

OFA status at 24 months of age is generally considered definitive of that dog’s hip status. However, there is a small chance a dog can go dysplastic later in life.

Visit OFA
(Immunoproliferative small intestinal disease, malabsorption, etc.)
Malabsorption is a chronic intestinal problem with symptoms including diarrhea, weight loss, loss of appetite, and, if unchecked, potentially death. Its frequency and mode of inheritance are unknown. Age of onset varies widely. It is an autoimmune problem, associated with the proliferation of lymphocytes and plasmocytes in the intestine. The mode of inheritance is not yet clearly understood, but it appears to be a hereditary problem.

There are many, many disorders and problems that cause similar symptoms, including disease, parasite infections, food allergies, and pancreatitis. For that reason, proper diagnosis by a veterinarian is very important. Not all appetite or intestinal problems in Basenjis are hereditary, and many are not serious if treated promptly.

IPSID is one of several different types of inflammatory bowel disease, which result in the dog not being able to utilize and absorb nutrients correctly from food. The human equivalent is Crohn’s disease or Irritable Bowel Disorder.

Progressive Retinal Atrophy (PRA)
Progressive retinal atrophy (PRA) is an eye condition in which the retina begins to deteriorate, causing visual loss and generally leading to blindness. A form of late onset progressive retinal deterioration is known to occur in Basenjis. Onset is typically late to very late, with typical onsets between ages 4 and 10, with some onsets reported between ages 3 and 13.

Basenjis can also have some unusual, but benign, forms of retinal pigmentation that can easily be confused with PRA or retinal degeneration.

It is not currently known if Basenji PRA is one disease or more than one. Mode of inheritance is presently unknown, although most forms of PRA are recessive.

Canine Eye Registration Foundation (CERF) exams by an American College of Veterinary Ophthalmologists (ACVO) certified veterinary ophthalmologist include examinations for PRA, as well as the other eye anomalies noted below. CERF exams are recommended annually for breeding stock. Dogs that test normal can receive a certificate for an additional cost.

A CERF exam indicates only the present state of a dog’s eyes. Since PRA onsets later in life, a CERF exam cannot predict whether or not a dog will develop PRA in the future.

About BHE

The Basenji Health Endowment is a 501 (c)(3) Public Charity founded by the Basenji Club of America in 1992 as a tool for collecting money and granting it to qualified researchers or institutions working on basenji-related health issues. Our status as a Public Charity is an incentive for people to give as their donations are tax deductible within the definitions of the law.

Officers & Board of Directors
President: Sally Wuornos
VP: Karla A. Schreiber, JD
Secretary: Anne Graves
Treasurer: Laura Mae Hesse
Directors: Lisa Auerbach, Damara Bolte, Jon Curby, Margaret Greenlee, Carrie Jones, Wanda Pooley, Laurie Stargell
To understand the difference between the BHE and the BCOA, you can read this article from the BCOA Bulletin. You will need Adobe Acrobat to read this file.