Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;51(3):466-469.
doi: 10.1111/age.12934. Epub 2020 Apr 2.

De novo stop-lost germline mutation in FGFR3 causes severe chondrodysplasia in the progeny of a Holstein bull

I M Häfliger  1 , A Letko  1 , L Murgiano  1   2   3 , C Drögemüller  1
Affiliations

De novo stop-lost germline mutation in FGFR3 causes severe chondrodysplasia in the progeny of a Holstein bull

I M Häfliger et al. Anim Genet. 2020 Jun.

Abstract

Fifteen cases of chondrodysplasia characterized by disproportionate dwarfism occurred in the progeny of a single Holstein bull. A de novo mutation event in the germline of the sire was suspected as cause. Whole-genome sequencing revealed a single protein-changing variant in the stop codon of FGFR3 gene on chromosome 6. Sanger sequencing of EDTA blood proved that this variant occurred de novo and segregates perfectly with the observed phenotype in the affected cattle family. FGFR3 is an important regulator gene in bone formation owing to its key role in the bone elongation induced by FGFR3-dimers. The detected paternally inherited stop-lost variant in FGFR3 is predicted to add 93 additional amino acids to the protein's C-terminus. This study provides a second example of a dominant FGFR3 stop-lost variant as a pathogenic mutation of a severe form of chondrodysplasia. Even though FGFR3 is known to be associated with dwarfism and growth disorders in human and sheep, this study is the first to describe FGFR3-associated chondrodysplasia in cattle.

Keywords: calf survival; dwarfism; genetic disorder; monogenic.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Beever J.E., Smit M.A., Meyers S.N., Hadfield T.S., Bottema C., Albretsen J. & Cockett N.E. (2006) A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep. Animal Genetics 37, 66-71.
    1. Boegheim I.J., Leegwater P.A., van Lith H.A. & Back W. (2017) Current insights into the molecular genetic basis of dwarfism in livestock. Veterinary Journal 224, 64-75.
    1. Buchan D.W.A. & Jones D.T. (2019) The PSIPRED protein analysis workbench: 20 years on. Nucleic Acids Resarch 47, W402-7.
    1. Cavanagh J.A.L., Tammen I., Windsor P.A., Bateman J.F., Savarirayan R., Nicholas F.W. & Raadsma H.W. (2007) Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN. Mammalian Genome 18, 808-14.
    1. Drögemüller C., Starke A., Schmidbauer S. & Wohlsein P. (2006) Kongenitaler disproportionaler Zwergwuchs bei Deutschen Holsteins. Tierärztliche Praxis Ausgabe Grosstiere Nutztiere 34, 148-54.

Substances

LinkOut - more resources