Identification of a HypomorphiciFANCG/iVariant in Bernese Mountain Dogs
| العنوان: | Identification of a HypomorphiciFANCG/iVariant in Bernese Mountain Dogs |
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| المؤلفون: | Katheryn Meek, Ya-Ting Yang, Marilia Takada, Maciej Parys, Marlee Richter, Alexander I. Engleberg, Tuddow Thaiwong, Rachel L. Griffin, Peter Z. Schall, Alana J. Kramer, Vilma Yuzbasiyan-Gurkan |
| المصدر: | Meek, K, Yang, Y-T, Takada, M, Parys, M, Richter, M, Engelberg, A, Thaiwong, T, Griffin, R, Schall, P, Kramer, A & Yuzbasiyan Gurkan, V 2022, ' Identification of a Hypomorphic FANCG Variant in Bernese Mountain Dogs ', Genes, vol. 13, no. 10, 1693 . https://doi.org/10.3390/genes13101693Test Genes; Volume 13; Issue 10; Pages: 1693 |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Bernese mountain dog, histiocytic sarcoma, fanconi anemia, cancer, comparative genetics, Histiocytic Sarcoma/genetics, Fanconi Anemia Complementation Group G Protein/genetics, Mice, Dogs, Fanconi Anemia, Fanconi Anemia/genetics, Mutation, Genetics, Humans, Animals, Histiocytic Sarcoma, Cisplatin, Fanconi Anemia Complementation Group G Protein, Genetics (clinical), Alleles |
| الوصف: | Bernese mountain dogs (BMDs), have an overall cancer incidence of 50%, half of which is comprised of an otherwise rare tumor, histiocytic sarcoma (HS). While recent studies have identified driver mutations in the MAPK pathway, identification of key predisposing genes has been elusive. Studies have identified several loci to be associated with predisposition to HS in BMDs, including near the MTAP/CDKN2A region, but no causative coding variant has been identified. Here we report the presence of a coding polymorphism in the gene encoding FANCG, near the MTAP/CDKN2A locus. This variant is in a conserved region of the protein and appears to be specific to BMDs. Canine fibroblasts derived from dogs homozygous for this variant are hypersensitive to cisplatin. We show this canine FANCG variant and a previously defined hypomorphic FANCG allele in humans impart similar defects in DNA repair. However, our data also indicate that this variant is neither necessary nor sufficient for the development of HS. Furthermore, BMDs homozygous for this FANCG allele display none of the characteristic phenotypes associated with Fanconi anemia (FA) such as anemia, short stature, infertility, or an earlier age of onset for HS. This is similar to findings in FA deficient mice, which do not develop overt FA without secondary genetic mutations that exacerbate the FA deficit. In sum, our data suggest that dogs with deficits in the FA pathway are, like mice, innately resistant to the development of FA. |
| وصف الملف: | application/pdf |
| تدمد: | 2073-4425 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8430517b02f33916ae4e83dcfe542442Test https://pubmed.ncbi.nlm.nih.gov/36292578Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8430517b02f33916ae4e83dcfe542442 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734425 |
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