OMIA:002380-9615 : Thyroid follicular cell carcinoma, susceptibility to in Canis lupus familiaris (dog)
Links to MONDO diseases: No links.
Mendelian trait/disorder: unknown
Mode of inheritance: Probably autosomal recessive
Considered a defect: yes
Species-specific description: Yu et al. (2021) described familial thyroid follicular cell carcinomas in Dutch German longhaired pointers (GLPs).
Yu et al. (2021) "investigated the genetic causes of the disease using a combined approach of genome-wide association study and runs of homozygosity (ROH) analysis based on 170k SNP array genotype data and whole-genome sequences."
Inheritance: Yu et al (2021): "45 of 54 histopathologically confirmed cases are closely related to a pair of first-half cousins in the past, indicating a familial disease. In addition, genetics contributed more to the thyroid follicular cell carcinoma than other factors by an estimated heritability of 0.62 based on pedigree. ... We observed a significant higher pedigree-based inbreeding coefficient in the affected dogs (mean F 0.23) compared to unaffected dogs (mean F 0.14), suggesting the contribution of inbreeding to tumour development."
Mapping: Yu et al. (2021): "A region 0-5 Mb on chromosome 17 was identified to be associated with the disease."
Molecular basis: Yu et al. (2021): "Whole-genome sequencing revealed many mutations fitting the recessive inheritance pattern in this region including two deleterious mutations in the TPO gene, chr17:800788G>A (686F>V) and chr17:805276C>T (845T>M). These two SNP were subsequently genotyped in 186 GLPs (59 affected and 127 unaffected) and confirmed to be highly associated with the disease. The recessive genotypes had higher relative risks of 16.94 and 16.64 compared to homozygous genotypes for the reference alleles, respectively."
Yu et al. (2022; BMC Genomics) "comprehensively investigated the somatic mutations that potentially contribute to the inherited tumor formation and progression using high depth whole-genome sequencing. A GNAS p.A204D missense mutation was identified in 4 out of 7 FCC tumors by whole-genome sequencing and in 20 out of 32 dogs' tumors by targeted sequencing."
Clinical features: Yu et al. (2021): "The age of diagnosis ranged between 4.5 and 13.5 years, and 76% of cases were diagnosed before 10 years of age, implying an early onset of disease."
German longhaired pointer.
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|TPO||thyroid peroxidase||Canis lupus familiaris||17||NC_051821.1 (830903..866744)||TPO||Homologene, Ensembl , NCBI gene|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2022||Yu, Y., Krupa, A., Keesler, R.I., Grinwis, G.C.M., de Ruijsscher, M., de Vos, J., Groenen, M.A.M., Crooijmans, R.P.M.A. :|
|Familial follicular cell thyroid carcinomas in a large number of Dutch German longhaired pointers. Vet Comp Oncol 20:227-234, 2022. Pubmed reference: 34464021 . DOI: 10.1111/vco.12769.|
|Yu, Y., Manders, F., Grinwis, G.C.M., Groenen, M.A.M., Crooijmans, R.P.M.A. :|
|A recurrent somatic missense mutation in GNAS gene identified in familial thyroid follicular cell carcinomas in German longhaired pointer dogs. BMC Genomics 23:669, 2022. Pubmed reference: 36151521 . DOI: 10.1186/s12864-022-08885-y.|
|2021||Yu, Y., Bovenhuis, H., Wu, Z., Laport, K., Groenen, M.A.M., Crooijmans, R.P.M.A. :|
|Deleterious mutations in the TPO gene associated with familial thyroid follicular cell carcinoma in Dutch German longhaired pointers. Genes (Basel) 12:997, 2021. Pubmed reference: 34209805 . DOI: 10.3390/genes12070997.|
- Created by Imke Tammen2 on 11 Aug 2021
- Changed by Imke Tammen2 on 11 Aug 2021
- Changed by Frank Nicholas on 27 Sep 2022