"Chondro" or MC is apparently limited to Alaskan Malamutes. Commonly known as "dwarfism," it can give affected dogs a range of conformation, particularly in the forequarters, from a very mild "Basset Hound" shape to severe deformity. Mode of inheritance is via a simple recessive gene. Education and tracking efforts of the Alaskan Malamute Club of America have kept the incidence low. Fortunately the mono-genetic source and simple inheritance makes this condition ideal for isolation and screening.

In 1996 AMRF entered into a long term partnership with a research team at Michigan State University to isolate the MC gene and produce a test to identify "carrier" dogs. As part of that arrangement, AMRF not only contributed funds but also facilitates the carrier- and dwarf-breedings necessary to produce the DNA samples critical to identifying the MC gene.

Photos courtesy of Canadian Veterinary Journal (above)
and AMCA (right)

Provided by Dr. Jacobs-Knoll, Technical Advisor to the AMRF
January 2003

Chondrodysplasia DNA Research - History:

2000 - Reached levels of enough dwarfs and carriers in the colony to begin DNA research at MSU.

2001 - MSU began testing specific areas of the canine genome to see if the ChD gene was linked to known markers. None of the markers worked - that means the ChD gene was not near or at known areas of the genome. This meant they had to start testing the entire K-9 genomefor the ChD gene.

2002 - MSU got though about 50% of the K-9 genome with no ChD gene found. Next step: go through the remaining genome to search for the gene.

When the markers they had identified as possible areas the ChD gene may have been did not work, the entire genome had to be searched. This is a difficult project. An analogy of how hard this is: It is like taking 300 marbles - 299 are green and 1 is red. Put them in a container, shake them up, turn off the lights and now which is red? Each marble must be taken out and evaluated to see if it is green or red. Now multiple this process by thousands with only 1 red marble, and it is easy to see how difficult this project is.

By the end of 2002, half the K-9 genome had been eliminated as possible ChD gene locations. Now they have the other ½ of the genome to search. We are closer now than ever, but we still have a ways to go.

2003 goals:

1. Produce 2 more litters of dwarfs/carriers to add DNA to the project to make the process easier and faster.
2. MSU has exhausted our original $20,000 contribution. Now AMRF needs to decide how to proceed with the project. AMRF needs to sit down with MSU and see how much more they think they will need to complete the genome testing. Then our options are:
   • Contact the AKC Health Foundation for matching funds to finish the project and help us keep track of its progress (ie. put some pressure on MSU).
   • Pay for the rest of the research ourself through AMRF funds.

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Previous Updates:

JAN 2002:

The year 2001 was a successful year for the Chondrodysplasia (Chd) DNA project. Our goals this year were:

1. To obtain additional DNA from puppies produced from carrier to carrier or carrier to dwarf breedings.
2. To begin research on the samples collected to determine the location of the Chd gene.

Our progress in 2001:

Michigan State University's genome research lab required a minimum of 3 to 5 litters of either carrier to carrier or carrier to dwarf breedings to produce as many dwarf puppies as possible for this research project to begin. Up until this past year, we did not have enough DNA from dwarfs for the study to begin the actual laboratory research. With the litters produced during the 2001 year as well as the litters from years previous, the study now has a total of 101 samples. Of those 101 samples, there are approximately 20 from dwarfs, and the remaining are from clear or carrier littermates and parents. There are a minimum number of dwarfs needed to begin the laboratory DNA study, and this number, although not ideally as high as they will need it to be, is adequate to begin the process.

During the next year (2002), AMRF and volunteers will continue to do their part to assure there are enough samples for this project so that it can be done as quickly as possible. The goal for this next year is to produce an additional 2 or 3 litters to provide more dwarfs for this research project. At that point, if minimally, 8 more dwarfs are produced from those 2 litters, we may not need to do additional litters. Michigan State's progress on locating the gene will determine if additional litters will need to be produced in the future.

Michigan State began comparing the dwarf DNA samples to known locations of the canine genome late this Summer. Because there are billions of locations of genes, they research literature on humans and other animals to determine if similar genes or genes that cause certain diseases with locations already known have been identified. They have to start somewhere, and one candidate gene (the CHH gene) of which the location is known is being compared to the samples. This may or may not be near the gene causing Chd in malamutes, and if determined not, then other candidate genes will be researched and compared to our samples.

As one can imagine, this is a long and tedious process. What this research project is attempting to do is identify the location of 1 gene out of a billion locations. That is like trying to find 1 person's location on the whole earth, but not having any idea of where that person may be because their address is unknown. MSU may get lucky in the next few months and find the gene, or it may take years. What is known, however, is that every day new genes are identified both in dogs and other species that will help provide potential candidate genes that might be linked or near the gene causing Chd in our breed.

We as the breed club, AMRF, and the many volunteers who are whelping these litters and adopting dogs for this project will do the best possible in providing addition DNA samples this next year to hopefully speed the process along.

Donations are still needed for this project to pay for veterinary reproduction assistance costs, caring for puppies who need additional care, and transportation expenses for the dogs when being bred, whelped, shipped to new homes, etc. Your help is greatly appreciated and will help speed up the process for the conclusion to this project.

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AUG 2001:

Topic One: Status

We are beginning a new phase of the project, which is the Lab / Mathematical side of the research. A very significant milestone! The minimal number of DNA families have been provided to MSU, and the researchers are beginning to process the DNA, fully understand the family trees, and lay out the analysis process, and tests for the research. We are hoping to have a very good progress report at the time of the National this year. The communication with the doctors at MSU is going very well and they are continuing to clarify their understanding of the family models of DNA, and checking to assure they have the models accurate. They are also beginning some top level tests which will help them narrow the search for the gene. They have also been very clear that we will need to continue to provide additional DNA families over the next year.

In Summary: The critical three DNA family samples have been completed, and ALL DNA samples and records have been turned over to the researchers at MSU. This reaches a key milestone in the project! We have made it to the lab stage of the project. The researchers are working to lay out the test / analysis strategy, confirming pedigree and relationship diagrams with the team, and beginning to work through some of the high level narrowing tests. In the mean time the AMRF team is still developing the colony with a few additional selective breedings to help with the analysis in later stages. One of those breedings is complete and another planned for later this fall.

Topic Two: Timing

The famous quote that Dr. Jacobs has consistently been shared with AMCA members for over 2 years now - that being "It is simply too early to tell when a CHD DNA test will be available." We are projecting the research tests to continue through the end of the year. IF the research goes as well as we hope, the test should be available 2002, however it could be longer. The 2002 timing for test availability has been a projected and consistent date for some time now (at least two national specialty presentations). Why wasn't this completed earlier --- In 1997, Dr. Jacobs was asked to become involved in the project and aid with the communication at MSU. In 1997 the definition of the 3 critical families of DNA was made. The AMCA community did not have a colony and resulted in the need to create the colony. This colony development started with the need to create carries that could then be utilized to create dwarves. Since that time, the team has been focused on creating that colony. You can do the math -- 4 years later, 3 generations (the original breedings to create carriers, carriers breed to create dwarves), and 3 critical DNA families. The team HAS accomplished a great deal.

Topic Three: CHD Colony Strategy

The strategy was decided on and implemented to carry out the breeding at key team members' homes and then place puppies' in good homes. We have never had a problem with any of the homes that puppies were placed in or ever had a problem using any of the key puppies for breedings when needed. It was a decision the team made, the colony is VERY safe, it has worked well, and the team does not have the future job of placing adult dogs in new homes. Anyone, including myself, could argue either side of this discussion. I believe, at the end of the day (which we are close to) the team made the right choice. Sally Stephens is our person responsible for the coordination of all puppy placements. If you are interested in or know of good potential homes she is still taking names for future.

AUG 2000: Funding: $30,000+ Completion Goal: 2002

In order to begin the DNA research, a minimum of 3 genetically specific litters need to be whelped. With the two current litters and two additional planned for fall 2000, then FINALLY, the Chd DNA research can begin. In order to cost effectively complete the research, a minimum number of litters are needed to begin the research and additional litters during the research process in order to complete the project.

We are hoping the MSU DNA research will begin late Fall 2000. It simply can't be predicted at this time the duration of the DNA research , but we are hopeful that a test will be available for late 2002.

APRIL 2000:

In 1999, 2 breedings were attempted, but both failed (probably due to the young age of the carriers). In Winter 2000, one of the carrier males was bred to a carrier bitch, and puppies were produced. Of that breeding, 1 dwarf bitch will be kept for breeding purposes. The other puppies' DNA swabs will be used for the research and then neutered and placed in pet homes. Another breeding was attempted. The litter was whelped on 4/20/00 by Sally Stephens; after a difficult C-section, only 2 puppies survived out of 13. A third breeding has been attempted this Spring as well with a carrier male to a carrier bitch, but it is unknown if the breeding has taken. Also, the dwarf father will be bred to his daughter this Spring, and hopefully they will produce puppies.

If the dwarf bitch's litter is large and one of the other two breedings takes as well, then FINALLY, the Chd DNA project research will begin! If not, then we need to get 1 more breeding before the researchers will begin the project. The reason they need a minimum number of breedings to take place is because the set-up time and charges are very expensive, thus, when doing the research, they need a minimum number of samples to make it cost effective to begin the process. (MSU still has almost all our original $20,000 "in the bank", waiting on the right time to spend it.)

I am hoping the MSU DNA research will begin by Fall 2000 (as long as one of the other breedings takes place and we get puppies.) It simply can't be predicted at this time when there will be a test available.

MARCH 2000:

The "foundation" carriers are now about 2 years old, and the first dwarf/carrier litter (6 surviving puppies) was born in January and seem to be doing well. Sherry Law bred and has raised the litter. There are two dwarfs in the litter and the Foundation plans to keep the female for possible future breeding (if needed by MSU.) The male dwarf unfortunately has a heart defect and will have to be euthanized. Sherry will place the remaining four puppies in the litter as 'pets'.

There is now only one other living female dwarf that we know of. That is the dwarf that Sally Stephens is keeping; she is expecting a dwarf/carrier litter to be born in late April. She will place them all in good homes.

If you have room for one of these "one of a kind" pups, or wish to raise any of the future members of the Foundation Chondro Colony, please contact Sally, Sherry, or any Board member.

NOVEMBER 1999:

The 3 carrier females have come into heat . One has already been bred back to her dwarf sire; the other two will be bred shortly. Breeding the carriers so young is obviously a concern, and the Foundation will be taking steps to ensure the continued health of the dams as well as of the resulting litters. MSU requires DNA samples from at least 15 dwarf puppies before they can begin isolating the Chd gene, so it is possible that these first 3 litters will provide enough samples to start. Completing the process with any degree of certainty will probably require samples from another 3 or 4 breeding combinations. If you would be interested in raising one of these litters, or if you would be willing to give one or more of the dogs a permanent home when the colony is no longer needed, contact Dr. Jacobs-Knoll.