@article{4ca9e57ee7114ae9bda11ddc847c1802,
title = "Potentially lethal cystic fibrosis gene variant in the orangutan",
abstract = "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.",
keywords = "Pongo, air sacculitis, bronchiectasis, cystic fibrosis transmembrane conductance regulator (CFTR) gene, respiratory",
author = "Taylor-Cousar, {Jennifer L.} and Evans, {Taylor A.} and Cutting, {Garry R.} and Neeraj Sharma",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Gilead Sciences Research Scholars Program in CF, National Jewish Health Department of Medicine, the Passamano/Sufian family, the Viola Vesta Coultre family to Jennifer L. Taylor-Cousar, Gilead Sciences Research Scholars Program and CF Foundation grant (SHARMA19I0) to Neeraj Sharma. The authors would like to thank all of the zoos and Graham Banes who contributed samples, the Orangutan Species Survival Plan Committee for their endorsement and their contribution of genealogical data for the project, and Isabella Passamano for data base organization and entry. The authors appreciate the suggestions of the American Journal of Primatology editor and reviewers to improve the manuscript. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Gilead Sciences Research Scholars Program in CF, National Jewish Health Department of Medicine, the Passamano/Sufian family, the Viola Vesta Coultre family to Jennifer L. Taylor‐Cousar, Gilead Sciences Research Scholars Program and CF Foundation grant (SHARMA19I0) to Neeraj Sharma. The authors would like to thank all of the zoos and Graham Banes who contributed samples, the Orangutan Species Survival Plan Committee for their endorsement and their contribution of genealogical data for the project, and Isabella Passamano for data base organization and entry. The authors appreciate the suggestions of the American Journal of Primatology editor and reviewers to improve the manuscript. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals, Inc.",
year = "2021",
month = dec,
doi = "10.1002/ajp.23097",
language = "English (US)",
volume = "83",
journal = "American journal of primatology",
issn = "0275-2565",
publisher = "John Wiley and Sons Inc.",
number = "12",
}