A frameshift deletion in F8 associated with hemophilia A in Labrador Retriever dogs

Author:

Hytönen Marjo K.123ORCID,Viitanen Sanna4,Hundi Sruthi123,Donner Jonas5,Lohi Hannes123,Kaukonen Maria123ORCID

Affiliation:

1. Department of Veterinary Biosciences University of Helsinki Helsinki Finland

2. Department of Medical and Clinical Genetics University of Helsinki Helsinki Finland

3. Folkhälsan Research Center Helsinki Finland

4. Department of Equine and Small Animal Medicine University of Helsinki Helsinki Finland

5. Wisdom Panel Research Team Wisdom Panel, Kinship Helsinki Finland

Abstract

AbstractHemophilia A is the most common inherited coagulation factor disorder in dogs. It manifests as excessive bleeding resulting from pathogenic variants in the X‐chromosomal F8 gene encoding coagulation factor VIII (FVIII) protein. In this study, we performed careful clinical phenotyping to confirm hemophilia A in two distinct Labrador Retriever (LR) pedigrees. Whole‐genome sequencing on an affected dog from litter 1 identified a case‐specific frameshift deletion variant in F8 predicted to cause a premature stop codon (c.2923_2924del, p.(E975Kfs*8)). This variant was hemizygous in all the affected males from litter 1 (n = 3), while all the unaffected LRs in the pedigree were heterozygous or wild‐type (n = 22). Additionally, screened samples from 199 LRs were all found to be wild‐type. As a result of this study, a gene test can now be developed to screen dogs before breeding to prevent further cases. However, it is important to note that the affected LR with decreased FVIII activity from litter 2 was wild‐type for the identified deletion variant, and no segregating F8 variants were detected when this dog's DNA sample was whole‐genome sequenced. Thus, the cause of decreased FVIII activity in this dog remains to be unraveled in future studies.

Funder

Academy of Finland

Helsinki Institute of Life Science, Helsingin Yliopisto

Jane ja Aatos Erkon Säätiö

Sigrid Juséliuksen Säätiö

Publisher

Wiley

Subject

Genetics,Animal Science and Zoology,General Medicine

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