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携带致心律失常性右室心肌病的倭黑猩猩(Pan paniscus)的遗传学分析。

Genetic analyses in a bonobo (Pan paniscus) with arrhythmogenic right ventricular cardiomyopathy.

机构信息

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Milwaukee County Zoo, Milwaukee, WI, 53226, USA.

出版信息

Sci Rep. 2018 Mar 12;8(1):4350. doi: 10.1038/s41598-018-22334-5.

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder that may lead to sudden death and can affect humans and other primates. In 2012, the alpha male bonobo of the Milwaukee County Zoo died suddenly and histologic evaluation found features of ARVC. This study sought to discover a possible genetic cause for ARVC in this individual. We sequenced our subject's DNA to search for deleterious variants in genes involved in cardiovascular disorders. Variants found were annotated according to the human genome, following currently available classification used for human diseases. Sequencing from the DNA of an unrelated unaffected bonobo was also used for prediction of pathogenicity. Twenty-four variants of uncertain clinical significance (VUSs) but no pathogenic variants were found in the proband studied. Further familial, functional, and bonobo population studies are needed to determine if any of the VUSs or a combination of the VUSs found may be associated with the clinical findings. Future genotype-phenotype establishment will be beneficial for the appropriate care of the captive zoo bonobo population world-wide as well as conservation of the bobono species in its native habitat.

摘要

致心律失常性右室心肌病(ARVC)是一种可能导致猝死的疾病,可影响人类和其他灵长类动物。2012 年,密尔沃基县动物园的阿尔法雄性倭黑猩猩突然死亡,组织学评估发现了 ARVC 的特征。本研究旨在发现该个体 ARVC 的可能遗传原因。我们对研究对象的 DNA 进行测序,以寻找与心血管疾病相关基因中的有害变异。根据人类基因组,对发现的变异进行注释,遵循目前用于人类疾病的分类。还对一只无相关疾病的倭黑猩猩的 DNA 进行测序,以预测其致病性。在研究的先证者中,发现了 24 种不确定的临床意义变异(VUS),但没有致病性变异。需要进行进一步的家族性、功能和倭黑猩猩群体研究,以确定发现的任何 VUS 或 VUS 组合是否与临床发现相关。未来的基因型-表型建立将有助于对全球圈养动物园倭黑猩猩种群进行适当的护理,以及保护其在原生栖息地的物种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f7f/5847517/023a4bdd3a2a/41598_2018_22334_Fig1_HTML.jpg

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