Table_1_Heritability and Pedigree Analyses of Hypertrophic Cardiomyopathy in Rhesus Macaques (Macaca Mulatta).XLSX

In a colony of rhesus macaques at California National Primate Research Center (CNPRC), naturally occurring hypertrophic cardiomyopathy (HCM) classified by left ventricular hypertrophy without obvious underlying diseases has been identified during necropsy over the last two decades. A preliminary pedigree analysis suggested a strong genetic predisposition of this disease with a founder effect. However, the mode of inheritance was undetermined due to insufficient pedigree data. Since 2015, antemortem examination using echocardiographic examination as well as other cardiovascular analyses have been performed on large numbers of rhesus macaques at the colony. Based on antemortem examination, HCM was diagnosed in additional 65 rhesus macaques. Using HCM cases diagnosed based on antemortem and postmortem examinations, the heritability (h2) was estimated to determine the degree of genetic and environmental contributions to the development of HCM in rhesus macaques at the CNPRC. The calculated mean and median heritability (h2) of HCM in this colony of rhesus macaques were 0.5 and 0.51 (95% confidence interval; 0.14–0.82), respectively. This suggests genetics influence development of HCM in the colony of rhesus macaques. However, post-translational modifications and environmental factors are also likely to contribute the variability of phenotypic expression. Based on the pedigree analysis, an autosomal recessive trait was suspected, but an autosomal dominant mode of inheritance with incomplete penetrance was also possible. Further investigation with more data from siblings, offspring, and parents of HCM-affected rhesus macaques are warranted. Importantly, the findings of the present study support conducting genetic investigations such as whole genome sequencing to identify the causative variants of inherited HCM in rhesus macaques.

在美国加利福尼亚国家灵长类动物研究中心（California National Primate Research Center, CNPRC）的恒河猴（rhesus macaques）种群中，过去二十年间的尸检工作里，发现了自然发生的肥厚型心肌病（hypertrophic cardiomyopathy, HCM）——该疾病以左心室肥厚为特征且无明确潜在病因。初步的谱系分析提示，该疾病存在强烈的遗传易感性，且存在奠基者效应（founder effect）。但由于谱系数据不足，其遗传模式尚未明确。自2015年起，该研究中心已对该种群中的大量恒河猴开展了超声心动图检查及其他心血管相关检测等生前评估。基于生前检查结果，又新增确诊了65例恒河猴肥厚型心肌病病例。结合生前及死后诊断的肥厚型心肌病病例，研究人员估算了遗传力（h²），以明确遗传与环境因素对该中心恒河猴肥厚型心肌病发生的贡献程度。本种群恒河猴肥厚型心肌病的平均遗传力与中位数遗传力分别为0.5与0.51（95%置信区间：0.14–0.82）。这表明遗传因素对该种群恒河猴肥厚型心肌病的发生具有显著影响。不过，翻译后修饰（post-translational modifications）与环境因素同样可能参与影响表型表达的差异。基于谱系分析，研究人员怀疑该疾病为常染色体隐性遗传性状，但不完全外显的常染色体显性遗传模式也存在可能性。后续仍需收集更多来自肥厚型心肌病患病恒河猴的同胞、后代及亲本的数据，以开展进一步研究。值得注意的是，本研究结果支持开展全基因组测序等遗传相关研究，以鉴定恒河猴遗传性肥厚型心肌病的致病变异。