Familial mitral valve prolapse in human beings has been associated with several genetic variants; however, in most cases, a known variant has not been identified. Dogs also have a naturally occurring form of familial mitral valve disease (MMVD) with similarities to the human disease. A shared genetic background and clinical phenotype of this disease in some dog breeds has indicated that the disease may share a common genetic cause. We evaluated DNA from 50 affected dogs from five different dog breeds in a whole genome sequencing approach to identify shared variants across and within breeds that could be associated with MMVD. No single causative genetic mutation was found from the 50 dogs with MMVD. Ten variants were identified in 37/50 dogs around and within the MED13L gene. These variants were no longer associated with MMVD when evaluated with a larger cohort including both affected and unaffected dogs. No high/moderate impact variants were identified in 10/10 miniature poodles, one was identified in 10/10 Yorkshire Terriers and 10/10 dachshunds, respectively, 14 were identified in 10/10 Miniature schnauzers, and 19 in 10/10 CKCS. Only one of these could be associated with the cardiac valve (Chr12:36801705, COL12A1; CKCS) but when evaluated in an additional 100 affected CKCS the variant was only identified in 84/100 affected dogs, perhaps indicating genetic heterogeneity in this disease. Our findings indicate that development of MMVD in the dog may be related to a combination of genetic and environmental factors that impact specific molecular pathways rather than a single shared genetic variant across or within breeds.

人类家族性二尖瓣脱垂与多种遗传变异有关。然而，在大多数情况下，尚未确定已知的变体。狗也有一种与人类疾病相似的家族性二尖瓣疾病 (MMVD) 的自然发生形式。在某些犬种中，这种疾病的共同遗传背景和临床表型表明该疾病可能具有共同的遗传原因。我们以全基因组测序方法评估了来自五个不同犬种的 50 只受影响犬的 DNA，以确定可能与 MMVD 相关的犬种之间和犬种内的共享变异。从 50 只患有 MMVD 的狗中没有发现单一的致病基因突变。在 MED13L 周围和内部的37/50只狗中发现了 10 种变异基因。当对包括受影响和未受影响的狗在内的更大队列进行评估时，这些变异不再与 MMVD 相关。在 10/10 迷你贵宾犬中未发现高/中度影响变异，分别在 10/10 约克夏梗和 10/10 腊肠犬中发现了一种，在 10/10 迷你雪纳瑞犬中发现了 14 种，在 10/10 CKCS 中发现了 19 种。其中只有一个可能与心脏瓣膜相关 (Chr12:36801705, COL12A1; CKCS )但是当在另外 100 只受影响的 CKCS 中进行评估时，仅在 84/100 只受影响的狗中发现了变异，这可能表明这种疾病的遗传异质性。我们的研究结果表明，犬 MMVD 的发展可能与影响特定分子途径的遗传和环境因素的组合有关，而不是与品种之间或品种内部的单一共享遗传变异有关。