دورية أكاديمية
Christmas disease in a Hovawart family resembling human hemophilia B Leyden is caused by a single nucleotide deletion in a highly conserved transcription factor binding site of the F9 gene promoter
| العنوان: | Christmas disease in a Hovawart family resembling human hemophilia B Leyden is caused by a single nucleotide deletion in a highly conserved transcription factor binding site of the F9 gene promoter |
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| المؤلفون: | Bertram Brenig, Lilith Steingräber, Shuwen Shan, Fangzheng Xu, Marc Hirschfeld, Reiner Andag, Mirjam Spengeler, Elisabeth Dietschi, Reinhard Mischke, Tosso Leeb |
| المصدر: | Haematologica, Vol 104, Iss 11 (2019) |
| بيانات النشر: | Ferrata Storti Foundation, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Hemophilia B is a classical monogenic, X-chromosomal, recessively transmitted bleeding disorder caused by genetic variants within the coagulation factor IX gene (F9). Although hemophilia B has been described in dogs, it has not yet been reported in the Hovawart breed. Here we describe the identification of a Hovawart family transmitting typical signs of an X-linked bleeding disorder. Five males were reported to suffer from recurrent hemorrhagic episodes. A blood sample from one of these males with only 2% of the normal concentration of plasma factor IX together with samples from seven relatives were provided. Next-generation sequencing of the mother and grandmother revealed a single nucleotide deletion in the F9 promoter. Genotyping of the deletion in 1,298 dog specimens including 720 Hovawarts revealed that the mutant allele was only present in the aforementioned Hovawart family. The deletion is located 73 bp upstream of the F9 start codon in the conserved overlapping DNA binding sites of hepatocyte nuclear factor 4α (HNF-4α) and androgen receptor (AR). The deletion only abolished binding of HNF-4α, while AR binding was unaffected as demonstrated by electrophoretic mobility shift assay using human HNF-4α and AR with double-stranded DNA probes encompassing the mutant promoter region. Luciferase reporter assays using wildtype and mutated promoter fragment constructs transfected into Hep G2 cells showed a significant reduction in expression from the mutant promoter. The data provide evidence that the deletion in the Hovawart family caused a rare type of hemophilia B resembling human hemophilia B Leyden. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/9134; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2018.215426 |
| URL الوصول: | https://doaj.org/article/b109c6afdccd4cf9b33376f22f76cd50 |
| رقم الأكسشن: | edsdoj.b109c6afdccd4cf9b33376f22f76cd50 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2018.215426 |