Clinical Features of English Bulldogs with Presumed Arrhythmogenic Right Ventricular Cardiomyopathy: 31 Cases (2001–2013)

Cunningham, Suzanne M.; Sweeney, Joseph T.; MacGregor, John; Barton, Bruce

doi:10.5326/jaaha-ms-6550

Cited by 20 publications

(13 citation statements)

References 25 publications

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“…In accordance, some breeds like Boxers and Bulldogs that have among the strongest founder events in our analysis are also known to be affected by high rates of genetic disorders. For instance, arrhythmogenic right ventricular cardiomyopathy that is a cardiac disease causing sudden death is seen at high frequency in both breeds 63,64 . The temporal distribution of founder events in dogs (~75-125 years ago) overlaps with the Victorian era when a large number of modern dog breeds were created in Great Britain in the context of popularizing dog-fancying and showing 52 .…”

Section: Discussionmentioning

confidence: 99%

Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

Tournebize¹,

Chu²,

Moorjani³

2020

Preprint

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Founder events play a critical role in shaping genetic diversity, impacting the fitness of a species and disease risk in humans. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods for characterizing founder events require large sample sizes or phased genomes. To learn about the frequency and evolutionary history of founder events, we introduce ASCEND (Allele Sharing Correlation for the Estimation of Non-equilibrium Demography), a flexible two-locus method to infer the age and strength of founder events. This method uses the correlation in allele sharing across the genome between pairs of individuals to recover signatures of past bottlenecks. By performing coalescent simulations, we show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios, with genotype or sequence data. We apply ASCEND to ~5,000 worldwide human samples (~3,500 present-day and ~1,500 ancient individuals), and ~1,000 domesticated dog samples. In both species, we find pervasive evidence of founder events in the recent past. In humans, over half of the populations surveyed in our study had evidence for a founder events in the past 10,000 years, associated with geographic isolation, modes of sustenance, and historical invasions and epidemics. We document that island populations have historically maintained lower population sizes than continental groups, ancient hunter-gatherers had stronger founder events than Neolithic Farmers or Steppe Pastoralists, and periods of epidemics such as smallpox were accompanied by major population crashes. Many present-day groups--including Central & South Americans, Oceanians and South Asians--have experienced founder events stronger than estimated in Ashkenazi Jews who have high rates of recessive diseases due to their history of founder events. In dogs, we uncovered extreme founder events in most groups, more than ten times stronger than the median strength of founder events in humans. These founder events occurred during the last 25 generations and are likely related to the establishment of dog breeds during Victorian times. Our results highlight a widespread history of founder events in humans and dogs, and provide insights about the demographic and cultural processes underlying these events.

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Section: Discussionmentioning

confidence: 99%

Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

Tournebize¹,

Chu²,

Moorjani³

2020

Preprint

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“…Thirteen of the dogs were reported “unknown breed”, 62 mixed breeds, and the remaining were named by breed. Of 305 dogs that had breeds listed ( Figure 3 ), 223 (73%) were identified as a breed predisposed to DCM (Golden Retrievers, Great Danes, Doberman Pinschers, Boxers, Cocker Spaniels, and Bulldogs) ( Calvert et al, 1997 ; Kittleson et al, 1997 ; Sisson et al, 2000 ; Broschk and Distl, 2005 ; Domanjko-Petric and Tomsic, 2008 ; Cunningham et al, 2018 ; Kaplan et al, 2018 ). Overrepresentation and breed reporting bias possibly inflated the number of reported cases ( FDA, 2019a ).…”

Section: Limitations To Current Fda Reportsmentioning

confidence: 99%

Review of canine dilated cardiomyopathy in the wake of diet-associated concerns

McCauley¹,

Clark²,

Quest³

et al. 2020

Journal of Animal Science

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Abstract Dilated cardiomyopathy (DCM) has been in the literature and news because of the recent opinion-based journal articles and public releases by regulatory agencies. DCM is commonly associated with a genetic predisposition in certain dog breeds and can also occur secondary to other diseases and nutritional deficiencies. Recent communications in veterinary journals have discussed a potential relationship between grain-free and/or novel protein diets to DCM, citing a subjective increase in DCM in dog breeds that are not known to have a genetic predisposition for the disease. This literature review describes clinical presentations of DCM, common sequelae, treatment and preventative measures, histopathologic features, and a discussion of the varied etiological origins of the disease. In addition, current literature limitations are addressed, in order to ascertain multiple variables leading to the development of DCM. Future studies are needed to evaluate one variable at a time and to minimize confounding variables and speculation. Furthermore, to prevent sampling bias with the current FDA reports, the veterinary community should be asked to provide information for all cases of DCM in dogs. This should include cases during the same time period, regardless of the practitioner’s proposed etiology, due to no definitive association between diets with specific characteristics, such as, but not limited to, grain-free diets and those containing legumes, novel protein diets, and those produced by small manufacturers to DCM in dogs. In summary, in order to determine if certain ingredients, categories of diets, or manufacturing processes are related to an increased risk of DCM, further studies investigating these variables are necessary.

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“…Currently, no STRN mutation for human ACM patients is listed in the HGMD or the ARVD/C Genetic Database 4 . In addition, ACM was described for English Bulldogs and Weimaraners (Eason et al, 2015;Cunningham et al, 2018). Corresponding to Boxer ACM, it was shown that ACM presented with right-ventricular dilation, thin right-ventricular wall diameter, ventricular tachycardia, and severe fibro-fatty replacement of the 4 https://molgenis136.gcc.rug.nl myocardium, which occurred spontaneously in domestic cats (Fox et al, 2000;Harvey et al, 2005;Ciaramella et al, 2009).…”

Section: Acm Animal Models Without Human Genetic Correlationmentioning

confidence: 99%

Genetic Animal Models for Arrhythmogenic Cardiomyopathy

Gerull

Brodehl

2020

Front. Physiol.

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Arrhythmogenic cardiomyopathy has been clinically defined since the 1980s and causes right or biventricular cardiomyopathy associated with ventricular arrhythmia. Although it is a rare cardiac disease, it is responsible for a significant proportion of sudden cardiac deaths, especially in athletes. The majority of patients with arrhythmogenic cardiomyopathy carry one or more genetic variants in desmosomal genes. In the 1990s, several knockout mouse models of genes encoding for desmosomal proteins involved in cell–cell adhesion revealed for the first time embryonic lethality due to cardiac defects. Influenced by these initial discoveries in mice, arrhythmogenic cardiomyopathy received an increasing interest in human cardiovascular genetics, leading to the discovery of mutations initially in desmosomal genes and later on in more than 25 different genes. Of note, even in the clinic, routine genetic diagnostics are important for risk prediction of patients and their relatives with arrhythmogenic cardiomyopathy. Based on improvements in genetic animal engineering, different transgenic, knock-in, or cardiac-specific knockout animal models for desmosomal and nondesmosomal proteins have been generated, leading to important discoveries in this field. Here, we present an overview about the existing animal models of arrhythmogenic cardiomyopathy with a focus on the underlying pathomechanism and its importance for understanding of this disease. Prospectively, novel mechanistic insights gained from the whole animal, organ, tissue, cellular, and molecular levels will lead to the development of efficient personalized therapies for treatment of arrhythmogenic cardiomyopathy.

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Clinical Features of English Bulldogs with Presumed Arrhythmogenic Right Ventricular Cardiomyopathy: 31 Cases (2001–2013)

Cited by 20 publications

References 25 publications

Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

Review of canine dilated cardiomyopathy in the wake of diet-associated concerns

Genetic Animal Models for Arrhythmogenic Cardiomyopathy

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