A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption).

Drögemüller, Michaela; Jagannathan, Vidhya; Howard, J.; Bruggmann, Rémy; Drögemüller, Cord; Ruetten, Maja; Leeb, Tosso; Kook, Peter H. (2014). A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption). Animal genetics, 45(1), pp. 148-150. Blackwell 10.1111/age.12094

[img] Text
age12094.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (192kB) | Request a copy

Mammals are unable to synthesize cobalamin or vitamin B12 and rely on the uptake of dietary cobalamin. The cubam receptor expressed on the intestinal endothelium is required for the uptake of cobalamin from the gut. Cubam is composed of two protein subunits, amnionless and cubilin, which are encoded by the AMN and CUBN genes respectively. Loss-of-function mutations in either the AMN or the CUBN gene lead to hereditary selective cobalamin malabsorption or Imerslund-Gräsbeck syndrome (IGS). We investigated Beagles with IGS and resequenced the whole genome of one affected Beagle at 15× coverage. The analysis of the AMN and CUBN candidate genes revealed a homozygous deletion of a single cytosine in exon 8 of the CUBN gene (c.786delC). This deletion leads to a frameshift and early premature stop codon (p.Asp262Glufs*47) and is, thus, predicted to represent a complete loss-of-function allele. We tested three IGS-affected and 89 control Beagles and found perfect association between the IGS phenotype and the CUBN:c.786delC variant. Given the known role of cubilin in cobalamin transport, which has been firmly established in humans and dogs, our data strongly suggest that the CUBN:c.786delC variant is causing IGS in the investigated Beagles.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Central Clinical Laboratory
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:

Drögemüller, Michaela; Jagannathan, Vidya; Howard, Judith; Bruggmann, Rémy; Drögemüller, Cord and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture

ISSN:

0268-9146

Publisher:

Blackwell

Language:

English

Submitter:

Susanne Portner

Date Deposited:

22 Aug 2014 16:00

Last Modified:

31 Dec 2019 07:54

Publisher DOI:

10.1111/age.12094

PubMed ID:

24164695

Uncontrolled Keywords:

Canis familiaris, WGS, Dog animal model, candidate gene, genetic testing, vitamin B12, whole-genome sequencing

BORIS DOI:

10.7892/boris.43851

URI:

https://boris.unibe.ch/id/eprint/43851

Actions (login required)

Edit item Edit item
Provide Feedback