Updated April 8, 2014 March, 2014: Dr. Lohi has released the following Report to the Canine
Health Foundation on the current progress of our research project. Report
to Grant Sponsor from Investigator:
“In the Alaskan Malamute chondrodysplasia study, we have been using two
complementary research methods to discover the causative mutation: exome
sequencing and DNA-marker based
genome-wide association mapping. Thus far we have analysed genome-wide data
from ten affected dogs and up to 87 healthy control dogs. Part of the
control cohort was obtained
from a previous cataract study. The Alaskan Malamute chondrodysplasia is
thought to have an autosomal recessive mode of inheritance and we have
performed our data analyses under this
model. We have now identified a chromosomal region that shows association to
the disease. This region was identified by using several different
genome-wide analysis approaches, which
included both basic case-control association and family-based methods. The
finding is still tentative because our sample cohort has some issues
concerning unwanted population
structure. The affected dogs form a separate cluster from the control
samples, which means that they come from a separate line of dogs than the
control dogs. This population structure
can have an effect to the results by introducing false positive findings
that are caused by the population difference and not by the difference in
affection status. To correct this problem, we
have recently genotyped a new sample set of seven affected and seven control
dogs but unfortunately half of these sample failed because of their poor
quality. We have previously
performed exome sequencing to one carrier dog and two affected dogs, and now
we are in theprocess of sequencing four additional affected and two
additional carrier dogs by using an
updated exome sequencing platform.
The main obstacle in this study has been the availability and quality of
samples. Many samples of affected dogs have been received as old DNA samples
that have had both low DNA-quality
and quantity. Furthermore, control dogs that are closely related to the
affected dogs have been difficult to obtain, and this has caused the
problems in population structure. Consequently, any
new samples from affected dogs and their relatives would be greatly
appreciated. However, people within the Alaskan Malamute breed have been
extremely supportive of the research
project, and we wish to warmly thank all who have contributed to the study
and helped us in obtaining samples.”
October, 2013: Dr. Lohi’s research group has just received a set of samples
from Dr. Venta’s original research project. This represents a number of
additional affected and carrier dogs and should greatly facilitate the
research project and progress.
November, 2012: Dr. Lohi has applied for and received an Acorn Grant
through the American Kennel Club’s Canine Health Foundation to help
facilitate the research project. This grant has been fully funded by the
Alaskan Malamute Research Foundation.
September, 2012: The researchers have checked 28 variants from the
exome-data in a bigger sample cohort but unfortunately none of these
variants showed perfect segregation with the disease. They are currently
performing the lab work to check another set of 27 variants (ioinformatician
re-analyzed the exome-data with another program and with some new
interesting variants that they are looking through).
July 8, 2012: The researchers have identified approximately 30 variants of
interest in our samples, and are running these through further analysis.
Additionally, they will be doing a SNP-chip genotyping study which will
hopefully increase our chances to find the causative mutation. Additional
new samples from carriers and an affected dog are being sent to the lab,
which will help Dr. Lohi’s group confirm any findings they may uncover. We
should know more in the coming few months. We have informed them that if any
funds are needed to accelerate the research, we will do what is needed to
provide these through the Canine Health Foundation grant process using our
Donor Advised Fund.
January, 2012: At the beginning of 2011, we were told that the researcher
at MSU who has been working on this project for years, Dr. Pat Venta, was
willing to collaborate with another researcher who had more advanced
technology in an effort to find this gene. Unfortunately, several months
later we were informed that he had decided against this collaboration and
wanted to pursue a grant on his own to do the research. At this time no
grant has been pursued. Because finding the gene for dwarfism is a priority,
we are exploring all other options for this research. Dr. Hannes Lohi at the
University of Helsinki discovered the gene for dwarfism in Norwegian
Elkhounds, but samples from our dwarfs have found that this is not the same
gene. However, his research team has taken on finding this gene in our breed–at no cost.We have gathered samples from all currently living dwarfs and dwarf carriers and have shipped the majority of these to their facility in Helsinki. These samples have been run through a whole exome scan platform, which is the most advanced genetic analysis available. They hope to have the results from this in a few months, at which time they will look for abnormalities which may represent the gene for the disease. How long this will take depends completely upon what the genetic results look like, but we feel confident that this team is doing everything that can be done on this project as quickly as is possible. They have been extremely responsive to any questions we have, and have been very proactive in asking us questions as well as getting any samples into their lab.
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