Academic Journal
A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy
| العنوان: | A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy |
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| المؤلفون: | Chew, Tracy, Haase, Bianca, Bathgate, Roslyn, Willet, Cali E., Kaukonen, Maria K., Mascord, Lisa J., Lohi, Hannes T., Wade, Claire M. |
| المساهمون: | Research Programs Unit, Departments of Faculty of Veterinary Medicine, Hannes Tapani Lohi / Principal Investigator, University of Helsinki, Research Programme for Molecular Neurology, Veterinary Biosciences, Medicum, Veterinary Genetics |
| بيانات النشر: | Genetics Society of America |
| سنة النشر: | 2017 |
| المجموعة: | Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: | Hungarian Puli, whole-genome sequencing, blindness, obesity, infertility, GENOME-WIDE ASSOCIATION, ROD-CONE DEGENERATION, DNA-SEQUENCING DATA, RETINITIS-PIGMENTOSA, DOG BREEDS, PRIMARY CILIUM, DOMESTIC DOG, MUTATION, THERAPY, MODEL, Biomedicine, Genetics, developmental biology, physiology |
| الوصف: | Progressive retinal atrophy is a common cause of blindness in the dog and affects >100 breeds. It is characterized by gradual vision loss that occurs due to the degeneration of photoreceptor cells in the retina. Similar to the human counterpart retinitis pigmentosa, the canine disorder is clinically and genetically heterogeneous and the underlying cause remains unknown for many cases. We use a positional candidate gene approach to identify putative variants in the Hungarian Puli breed using genotyping data of 14 family-based samples (CanineHD BeadChip array, Illumina) and whole-genome sequencing data of two proband and two parental samples (Illumina HiSeq 2000). A single nonsense SNP in exon 2 of BBS4 (c.58A > T, p.Lys20*) was identified following filtering of high quality variants. This allele is highly associated (P-CHISQ = 3.425e(-14), n = 103) and segregates perfectly with progressive retinal atrophy in the Hungarian Puli. In humans, BBS4 is known to cause Bardet-Biedl syndrome which includes a retinitis pigmentosa phenotype. From the observed coding change we expect that no functional BBS4 can be produced in the affected dogs. We identified canine phenotypes comparable with Bbs4-null mice including obesity and spermatozoa flagella defects. Knockout mice fail to form spermatozoa flagella. In the affected Hungarian Puli spermatozoa flagella are present, however a large proportion of sperm are morphologically abnormal and ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-85-02-17821-2 85-02-17821-0 |
| Relation: | Chew , T , Haase , B , Bathgate , R , Willet , C E , Kaukonen , M K , Mascord , L J , Lohi , H T & Wade , C M 2017 , ' A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy ' , G3 - Genes genomes genetics , vol. 7 , no. 7 , pp. 2327-2335 . https://doi.org/10.1534/g3.117.043109; ORCID: /0000-0002-2146-4694/work/65309040; http://hdl.handle.net/10138/205634; 68323320-0d27-4623-a630-079f850e28a0; 85021782106; 000404991600029 |
| الاتاحة: | http://hdl.handle.net/10138/205634 |
| Rights: | cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| رقم الانضمام: | edsbas.383317FC |
| قاعدة البيانات: | BASE |
| ردمك: | 9788502178212 8502178210 |
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