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Open AccessArticle

YARS2 Missense Variant in Belgian Shepherd Dogs with Cardiomyopathy and Juvenile Mortality

1
Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
2
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
3
Department/Hospital for Companion Animals and Horses, University Clinic for Small Animals, Internal Medicine Small Animals, University of Veterinary Medicine, 1210 Vienna, Austria
4
Institute of Veterinary Pathology, Justus-Liebig-University Giessen, 35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
These two authors contributed equally to this paper.
Genes 2020, 11(3), 313; https://doi.org/10.3390/genes11030313
Received: 12 February 2020 / Revised: 9 March 2020 / Accepted: 10 March 2020 / Published: 14 March 2020
(This article belongs to the Special Issue Genes at Ten)
Dog puppy loss by the age of six to eight weeks after normal development is relatively uncommon. Necropsy findings in two spontaneously deceased Belgian Shepherd puppies indicated an abnormal accumulation of material in several organs. A third deceased puppy exhibited mild signs of an inflammation in the central nervous system and an enteritis. The puppies were closely related, raising the suspicion of a genetic cause. Pedigree analysis suggested a monogenic autosomal recessive inheritance. Combined linkage and homozygosity mapping assigned the most likely position of a potential genetic defect to 13 genome segments totaling 82 Mb. The genome of an affected puppy was sequenced and compared to 645 control genomes. Three private protein changing variants were found in the linked and homozygous regions. Targeted genotyping in 96 Belgian Shepherd dogs excluded two of these variants. The remaining variant, YARS2:1054G>A or p.Glu352Lys, was perfectly associated with the phenotype in a cohort of 474 Belgian Shepherd dogs. YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase 2 and the predicted amino acid change replaces a negatively charged and evolutionary conserved glutamate at the surface of the tRNA binding domain of YARS2 with a positively charged lysine. Human patients with loss-of-function variants in YARS2 suffer from myopathy, lactic acidosis, and sideroblastic anemia 2, a disease with clinical similarities to the phenotype of the studied dogs. The carrier frequency was 27.2% in the tested Belgian Shepherd dogs. Our data suggest YARS2:1054G>A as the candidate causative variant for the observed juvenile mortality. View Full-Text
Keywords: Canis lupus familiaris; whole genome sequence; animal model; precision medicine; mitochondrium; translation; Groenendael; Laekenois; Malinois; Tervueren Canis lupus familiaris; whole genome sequence; animal model; precision medicine; mitochondrium; translation; Groenendael; Laekenois; Malinois; Tervueren
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MDPI and ACS Style

Gurtner, C.; Hug, P.; Kleiter, M.; Köhler, K.; Dietschi, E.; Jagannathan, V.; Leeb, T. YARS2 Missense Variant in Belgian Shepherd Dogs with Cardiomyopathy and Juvenile Mortality. Genes 2020, 11, 313. https://doi.org/10.3390/genes11030313

AMA Style

Gurtner C, Hug P, Kleiter M, Köhler K, Dietschi E, Jagannathan V, Leeb T. YARS2 Missense Variant in Belgian Shepherd Dogs with Cardiomyopathy and Juvenile Mortality. Genes. 2020; 11(3):313. https://doi.org/10.3390/genes11030313

Chicago/Turabian Style

Gurtner, Corinne; Hug, Petra; Kleiter, Miriam; Köhler, Kernt; Dietschi, Elisabeth; Jagannathan, Vidhya; Leeb, Tosso. 2020. "YARS2 Missense Variant in Belgian Shepherd Dogs with Cardiomyopathy and Juvenile Mortality" Genes 11, no. 3: 313. https://doi.org/10.3390/genes11030313

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