Next Article in Journal
Multiple Isolated Transcription Factors Act as Switches and Contribute to Species Uniqueness
Next Article in Special Issue
Correction: Ramzan F. et al. “Combining Random Forests and a Signal Detection Method Leads to the Robust Detection of Genotype-Phenotype Associations” Genes, 2020, 11, 892
Previous Article in Journal
Differences in Placental Imprinted Gene Expression across Preeclamptic and Non-Preeclamptic Pregnancies
Previous Article in Special Issue
Exploring the Regulatory Potential of Long Non-Coding RNA in Feed Efficiency of Indicine Cattle
Open AccessArticle

Deleterious AGXT Missense Variant Associated with Type 1 Primary Hyperoxaluria (PH1) in Zwartbles Sheep

1
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
2
Royal GD, Postbus 9, 7400 AA Deventer, The Netherlands
3
Farm Post Mortems Ltd., Hamsterley, Bishop Auckland, County Durham DL13 3QF, UK
4
SRUC Consulting Veterinary Services, Pentlands Science Park, Bush Estate Loan, Penicuik, Midlothian EH26 0PZ, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2020, 11(10), 1147; https://doi.org/10.3390/genes11101147
Received: 30 August 2020 / Revised: 15 September 2020 / Accepted: 26 September 2020 / Published: 29 September 2020
(This article belongs to the Special Issue Genetics and Genomics Applied to Livestock Production)
Severe oxalate nephropathy has been previously reported in sheep and is mostly associated with excessive oxalate in the diet. However, a rare native Dutch breed (Zwartbles) seems to be predisposed to an inherited juvenile form of primary hyperoxaluria and no causative genetic variant has been described so far. This study aims to characterize the phenotype and genetic etiology of the inherited metabolic disease observed in several purebred Zwartbles sheep. Affected animals present with a wide range of clinical signs including condition loss, inappetence, malaise, and, occasionally, respiratory signs, as well as an apparent sudden unexpected death. Histopathology revealed widespread oxalate crystal deposition in kidneys of the cases. Whole-genome sequencing of two affected sheep identified a missense variant in the ovine AGXT gene (c.584G>A; p.Cys195Tyr). Variants in AGXT are known to cause type I primary hyperoxaluria in dogs and humans. Herein, we present evidence that the observed clinicopathological phenotype can be described as a form of ovine type I primary hyperoxaluria. This disorder is explained by a breed-specific recessively inherited pathogenic AGXT variant. Genetic testing enables selection against this fatal disorder in Zwartbles sheep as well as more precise diagnosis in animals with similar clinical phenotype. Our results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 001672-9940). View Full-Text
Keywords: Ovis aries; oxalate nephropathy; whole-genome sequencing; metabolic disease; precision medicine; genetic test Ovis aries; oxalate nephropathy; whole-genome sequencing; metabolic disease; precision medicine; genetic test
Show Figures

Figure 1

MDPI and ACS Style

Letko, A.; Dijkman, R.; Strugnell, B.; Häfliger, I.M.; Paris, J.M.; Henderson, K.; Geraghty, T.; Orr, H.; Scholes, S.; Drögemüller, C. Deleterious AGXT Missense Variant Associated with Type 1 Primary Hyperoxaluria (PH1) in Zwartbles Sheep. Genes 2020, 11, 1147.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop