A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death

Meurs, Kathryn M.; Friedenberg, Steven G.; Kolb, Justin; Saripalli, Chandra; Tonino, Paola; Woodruff, Katie; Olby, Natasha J.; Keene, Bruce W.; Adin, Darcy B.; Yost, Oriana; DeFrancesco, Teresa C.; Lahmers, Sunshine; Tou, Sandra; Shelton, G. Diane; Granzier, Henk

doi:10.1007/s00439-019-01973-2

Cited by 50 publications

(44 citation statements)

References 51 publications

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“…Canine dilated cardiomyopathy (DCM) represents the second most common acquired heart disease in dogs and has multiple identified etiologies [1][2][3]. While DCM of genetic origins have been described for some breeds based upon discovered mutations or observed heritability and pattern of inheritance, determining etiology of DCM when observed outside of these breeds is challenging [4][5][6][7][8][9][10][11][12][13][14][15][16]. Nutritionally mediated DCM has been described across a variety of species including dogs and is most historically linked to taurine deficiency [17][18][19][20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study

Ontiveros

Whelchel

et al. 2020

PLoS ONE

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Introduction A surge in Food and Drug Administration (FDA) consumer complaints identified concerns that legume-rich, grain-free diets were associated with nutritionally-mediated dilated cardiomyopathy (DCM). Golden retrievers represent the most reported breed affected by this condition and previous studies documented the disease is responsive to dietary change and taurine supplementation. Although dietary findings across cases are compelling, prospective studies with control groups are lacking. The role of diet in developing taurine deficiency and echocardiographic changes consistent with DCM in healthy dogs is unknown. Objectives We hypothesized that golden retrievers eating non-traditional diets are at a higher risk of having taurine deficiency and nutritionally-mediated DCM compared with those eating traditional commercial diets. We aimed to compare taurine concentrations and echocardiographic indices of systolic function between golden retrievers in each diet group and elucidate associations between diet and these variables. Additionally, we aimed to generate breed-specific reference intervals for whole blood and plasma taurine concentrations. Animals 86 golden retrievers.

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Section: Introductionmentioning

confidence: 99%

Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study

Ontiveros

Whelchel

et al. 2020

PLoS ONE

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“…Furthermore, outside of ESS, there have been no breed-specific analyses. Considering that different WGS efforts in dogs have recently proven to be advantageous in elucidating genetic susceptibility to disease [22][23][24][25][26][27], differences in body types [28], as well as adaptions against parasites [29], we have compiled and processed WGS data to begin the exploration of breed-specific CMT-risk alleles and, in this initial report, to specifically reveal the coding variants detected in orthologs of the high-risk human breast cancer susceptibility genes.…”

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing for the investigation of canine mammary tumor inheritance - an initial assessment of high-risk breast cancer genes reveal BRCA2 and STK11 variants potentially associated with risk in purebred dogs

Huskey

Goebel

Lloveras-Fuentes

et al. 2020

Canine Genet Epidemiol

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Background: Although, in general, cancer is considered a multifactorial disease, clustering of particular cancers in pedigrees suggests a genetic predisposition and could explain why some dog breeds appear to have an increased risk of certain cancers. To our knowledge, there have been no published reports of whole genome sequencing to investigate inherited canine mammary tumor (CMT) risk, and with little known about CMT genetic susceptibility, we carried out whole genome sequencing on 14 purebred dogs diagnosed with mammary tumors from four breedspecific pedigrees. Following sequencing, each dog's data was processed through a bioinformatics pipeline. This initial report highlights variants in orthologs of human breast cancer susceptibility genes. Results: The overall whole genome and exome coverage averages were 26.0X and 25.6X, respectively, with 96.1% of the genome and 96.7% of the exome covered at least 10X. Of the average 7.9 million variants per dog, initial analyses involved surveying variants in orthologs of human breast cancer susceptibility genes, BRCA1, BRCA2, CDH1, PTEN, STK11, and TP53, and identified 19 unique coding variants that were validated through PCR and Sanger sequencing. Statistical analyses identified variants in BRCA2 and STK11 that appear to be associated with CMT, and breed-specific analyses revealed the breeds at the highest risk. Several additional BRCA2 variants showed trends toward significance, but have conflicting interpretations of pathogenicity, and correspond to variants of unknown significance in humans, which require further investigation. Variants in other genes were noted but did not appear to be associated with disease.

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“…Briefly, a fragment library with average insert size of ∼680 bp was prepared from which ∼125 million 2 X 150 bp paired-end reads were generated, corresponding to roughly 17x genome-wide coverage. The reads were mapped against the dog reference genome assembly (CanFam3.1) as described (28,29)…”

Section: Whole Genome Sequencingmentioning

confidence: 99%

Sarcoglycan A Mutation in Miniature Dachshund Dogs Causes Limb Girdle Muscular Dystrophy 2D

Mickelson

Minor

Guo

et al. 2020

Preprint

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BackgroundA cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria and markedly elevated serum creatine kinase activities were identified. MethodsMuscle biopsy histopathology, immunofluorescence microscopy, and western blotting, were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis.ResultsMuscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene ( SGCA ). Affected dachshunds were confirmed on several continents. ConclusionsThis first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.

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A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death

Cited by 50 publications

References 51 publications

Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study

Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study

Whole genome sequencing for the investigation of canine mammary tumor inheritance - an initial assessment of high-risk breast cancer genes reveal BRCA2 and STK11 variants potentially associated with risk in purebred dogs

Sarcoglycan A Mutation in Miniature Dachshund Dogs Causes Limb Girdle Muscular Dystrophy 2D

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