A syndrome of chronic upper and lower airway disease leading to increased morbidity and mortality occurs primarily in captive orangutans. Similarities in symptoms to the inherited human respiratory disease, cystic fibrosis, led us to hypothesize that orangutan respiratory disease is a result of variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We identified the nonsense variant, c.484A>T (p.Lys162X), in heterozygosity in an unaffected orangutan. Analysis of the pedigree of this orangutan confirmed that both his sire and deceased fetus also harbored the c.484A>T allele. An expression minigene harboring c.484A>T produced no full-length CFTR protein in HEK293 cells. Finally, the c.484A>T CFTR messenger RNA abundance was severely reduced in primary nasal epithelial cells of the orangutan indicating that c.484A>T (p.Lys162X) is potentially lethal. Genetic screening of the captive orangutan population could be used to prevent transmission of this potentially lethal variant, and thus aid in the conservation of this critically endangered species.

中文翻译：

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猩猩中潜在致命的囊性纤维化基因变异

导致发病率和死亡率增加的慢性上呼吸道和下呼吸道疾病综合征主要发生在圈养猩猩身上。与遗传性人类呼吸道疾病囊性纤维化症状的相似性使我们假设猩猩呼吸道疾病是囊性纤维化跨膜电导调节因子 (CFTR) 基因变异的结果。我们在未受影响的猩猩中以杂合性鉴定了无义变体 c.484A>T (p.Lys162X)。对这只猩猩的谱系分析证实，他的父亲和死去的胎儿也携带 c.484A>T 等位基因。含有 c.484A>T 的表达小基因在 HEK293 细胞中不产生全长 CFTR 蛋白。最后，在猩猩的原代鼻上皮细胞中，c.484A>T CFTR 信使 RNA 丰度严重降低，表明 c. 484A>T (p.Lys162X) 可能是致命的。圈养猩猩种群的基因筛查可用于防止这种潜在致命变异的传播，从而有助于保护这种极度濒危的物种。