A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy.

Steffen, Frank; Bilzer, Thomas; Brands, Jan; Golini, Lorenzo; Jagannathan, Vidhya; Wiedmer, Michaela; Drögemüller, Michaela; Drögemüller, Cord; Leeb, Tosso (2015). A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy. G3 Genes Genomes Genetics, 5(12), pp. 2611-2617. Genetics Society of America 10.1534/g3.115.021923

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A novel canine muscular dystrophy in Landseer dogs was observed. We had access to five affected dogs from two litters. The clinical signs started at a few weeks of age and the severe progressive muscle weakness led to euthanasia between 5 and 15 months of age. The pedigrees of the affected dogs suggested a monogenic autosomal recessive inheritance of the trait. Linkage and homozygosity mapping indicated two potential genome segments for the causative variant on chromosomes 10 and 31 harboring a total of 4.8 Mb of DNA or 0.2% of the canine genome. Using the illumina sequencing technology we obtained a whole genome sequence from one affected Landseer. Variants were called with respect to the dog reference genome and compared to the genetic variants of 170 control dogs from other breeds. The affected Landseer dog was homozygous for a single private non-synonymous variant in the critical intervals, a nonsense variant in the COL6A1 gene (Chr31:39,303,964G>T; COL6A1:c.289G>T; p.E97*). Genotypes at this variant showed perfect concordance with the muscular dystrophy phenotype in all five cases and more than one thousand control dogs. Variants in the human COL6A1 gene cause Bethlem myopathy or Ullrich congenital muscular dystrophy. We therefore conclude that the identified canine COL6A1 variant is most likely causative for the observed muscular dystrophy in Landseer dogs. Based on the nature of the genetic variant in Landseer dogs and their severe clinical phenotype these dogs represent a model for human Ullrich congenital muscular dystrophy.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Jagannathan, Vidya; Wiedmer, Michaela; Drögemüller, Michaela; Drögemüller, Cord and Leeb, Tosso

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health

ISSN:

2160-1836

Publisher:

Genetics Society of America

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

19 Oct 2015 12:07

Last Modified:

16 Dec 2015 01:30

Publisher DOI:

10.1534/g3.115.021923

PubMed ID:

26438297

Uncontrolled Keywords:

Mendelian traits; animal model; dog; veterinary genetics; whole genome sequencing

BORIS DOI:

10.7892/boris.72278

URI:

https://boris.unibe.ch/id/eprint/72278

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