Possible genetic link found between hypothyro


image: Three of these older golden retrievers provided blood samples for a study that found a possible genetic link between hypothyroidism and the development of T-zone lymphoma in dogs.
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Credit: Sallie Cox

DENVER / September 14, 2020 – A genetic mutation could be the reason dogs with hypothyroidism are less likely to develop T-zone lymphoma (TZL). This is the discovery of researchers funded by the Morris Animal Foundation at Colorado State University who tried to identify genetic risk factors for TZL using a genome-wide association study (GWAS) and subsequent targeted sequencing. They recently published their results in the journal BMC Genomics.

“Golden retrievers are predisposed to so many cancers,” said Dr Julia Labadie, an epidemiologist with the Morris Animal Foundation, who conducted the study as part of her doctoral work. “Any piece of the puzzle we can solve to help us understand why can really help this breed. Of course, golden retrievers aren’t the only dogs with this cancer, so what we’re learning has implications for all dogs at risk for TZL.

The published study follows a publication 2019 from the same team that examined environmental and health history associations in golden retrievers with TZL. The team found that hypothyroidism and omega-3 supplementation are associated with a decreased risk of TZL and suggested a genetic predisposition for TZL.

“This gives us additional information that we can add to future studies to ultimately help us understand why dogs get this and other cancers,” said Dr. Janet Patterson-Kane, Scientific Director of the Morris Animal Foundation. “Through continuous research, we are making progress in the development of preventive measures, earlier diagnosis and effective treatments. “

The team used a subset of banked blood samples from the original study to more closely search for a genetic explanation for their initial findings. The samples used came from 95 dogs positive for TZL, 142 from dogs which possessed T-zone cells which could be precancerous and 101 from a control group of dogs at least 9 years old and without the disease. .

The researchers extracted DNA from each sample and genotyped it to identify areas of dogs’ chromosomes associated with having the disease or not. A region of interest has been found in chromosome 8 which has an association with the regulation of thyroid hormones. Although variation in genes associated with thyroid function has not yet been confirmed, the identification of the region containing the thyroid hormone genes in the study of genetic risk factors as well as hypothyroidism in the study of Environmental risk factors strongly suggest that this area of ​​the dog’s genome is a clue to the underlying causes of T-zone lymphoma.

“This study illustrates the value of the combined analysis of genetic and environmental risk factors, because the identification of hypothyroidism in the environmental study, as well as a genetic region that governs thyroid function in the genetic study,” highlights the importance of this part of the dog’s genome in this disease, ”said Dr. Anne Avery, professor in the Department of Microbiology, Immunology and Pathology at Colorado State University. “The relevant genes may be the thyroid function genes themselves, or other genes in the region, but the strong evidence from the combined studies on the importance of this genetic region means we can be sure that attention increased on this area will be fruitful. “

The CSU team also found four variants on chromosome 14 that were associated with an increased risk of TZL. These same variants were previously associated with the risk of mast cell tumors in golden retrievers, which may suggest a common mechanism underlying the development of both cancers. This independent study from the Broad Institute used similar genotyping methods. The CSU team, however, did not find that dogs with the chromosomal variants were likely to have both tumors.

T-zone lymphoma is a slowly progressive form of cancer that usually develops in older dogs, accounting for about 12% of canine lymphoma cases. It is much more common in golden retrievers than any other breed, with golden retrievers accounting for over 40% of all reported cases.

Most of the golden retrievers in the control group for this study were from the Morris Animal Foundation’s Canine Lifetime Health project. This is a registry of dogs whose owners want to participate in clinical trials and other studies aimed at improving canine health. Many dogs entered the registry during the Morris Animal Foundation’s recruiting phase Golden Retriever Lifetime Study, but were too old to participate in the study at the time of enrollment.

About the Morris Foundation for Animals

The Morris Animal Foundation’s mission is to connect science and resources to advance animal health. Founded by a veterinarian in 1948, we fund and conduct critical health studies for the benefit of all animals. Learn more about morrisanimalfoundation.org.

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