A De Novo Mutation in COL1A1 in a Holstein Calf with Osteogenesis Imperfecta Type II

Jacinto, Joana G. P.; Häfliger, Irene M.; McEvoy, Fintan J.; Drögemüller, Cord; Agerholm, Jørgen S. (2021). A De Novo Mutation in COL1A1 in a Holstein Calf with Osteogenesis Imperfecta Type II. Animals, 11(2) MDPI 10.3390/ani11020561

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Osteogenesis imperfecta (OI) type II is a genetic connective tissue disorder characterized by bone fragility, severe skeletal deformities and shortened limbs. OI usually causes perinatal death of affected individuals. OI type II diagnosis in humans is established by the identification of heterozygous mutations in genes coding for collagens. The purpose of this study was to characterize the pathological phenotype of an OI type II-affected neonatal Holstein calf and to identify the causative genetic variant by whole-genome sequencing (WGS). The calf had acute as well as intrauterine fractures, abnormally shaped long bones and localized arthrogryposis. Genetic analysis revealed a private heterozygous missense variant in COL1A1 (c.3917T>A) located in the fibrillar collagen NC1 domain (p.Val1306Glu) that most likely occurred de novo. This confirmed the diagnosis of OI type II and represents the first report of a pathogenic variant in the fibrillar collagen NC domain of COL1A1 associated to OI type II in domestic animals. Furthermore, this study highlights the utility of WGS-based precise diagnostics for understanding congenital disorders in cattle and the need for continued surveillance for rare lethal genetic disorders in cattle.

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)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Häfliger, Irene Monika and Drögemüller, Cord

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2076-2615

Publisher:

MDPI

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

24 Mar 2021 17:31

Last Modified:

24 Mar 2021 17:31

Publisher DOI:

10.3390/ani11020561

PubMed ID:

33672767

BORIS DOI:

10.48350/152929

URI:

https://boris.unibe.ch/id/eprint/152929

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