Detection of two Alu insertions in the CFTR gene

Chen, Jian-Min, Masson, Emmanuelle, Macek, Milan, Raguénès, Odile, Piskackova, Tereza, Fercot, Brigitte, Fila, Libor, Cooper, David Neil ORCID: https://orcid.org/0000-0002-8943-8484, Audrézet, Marie-Pierre and Férec, Claude 2008. Detection of two Alu insertions in the CFTR gene. Journal of Cystic Fibrosis 7 (1) , pp. 37-43. 10.1016/j.jcf.2007.04.001

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Abstract

Background LINE-1 (long interspersed element-1) or L1-mediated retrotransposition is a potent force in human genome evolution and an occasional cause of human genetic disease. Since the first report of two de novo L1 insertions in the F8 gene causing hemophilia A, more than 50 L1-mediated retrotranspositional events have been identified as causing human genetic disease. However, a significant bias has generally militated against the detection of these pathological events at autosomal loci. Based upon this and other observations, we surmised that some previously unresolved cystic fibrosis chromosomes might carry hitherto undetected L1-mediated retrotranspositional insertions at the CFTR locus. This study represents an attempt to identify such mutational events. Methods 100 previously unresolved cystic fibrosis chromosomes were carefully reanalyzed using quantitative high-performance liquid chromatography (QHPLC). Results Two simple Alu insertions were identified in the CFTR gene, within exons 16 and 17b respectively. Conclusions Our findings have not only revealed a previously unknown mutational mechanism responsible for cystic fibrosis but also represent an important addition to the already diverse spectrum of known CFTR gene mutations. Experience with the CFTR gene suggests that pathological L1-mediated retrotranspositional events may also have been overlooked at other gene loci and should always be considered in cases that appear to be refractory to analysis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Uncontrolled Keywords:	Alu sequence, cystic fibrosis, gross insertion, L1, LINE-1, retrotransposition
Publisher:	Elsevier
ISSN:	1569-1993
Last Modified:	20 Oct 2022 07:39
URI:	https://orca.cardiff.ac.uk/id/eprint/25991

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