Retrotransposable genetic elements causing neutrophil defects.

Research paper by Dirk D Roos, Martin M de Boer

Indexed on: 19 May '18Published on: 19 May '18Published in: European Journal of Clinical Investigation


Retrotransposable elements are stretches of DNA that encode proteins with the inherent ability to insert their own RNA or another RNA by reverse transcriptase as DNA into a new genomic location. In humans, the only autonomous retrotransposable elements are members of the Long INterspersed Element-1 (LINE-1) family. LINE-1s may cause gene inactivation and human disease. We present a brief summary of the published knowledge about LINE-1s in humans and the RNAs that these elements can transpose, and we focus on the effect of LINE-1-mediated retrotransposition on human neutrophil function. Retrotransposons can cause genetic disease by two primary mechanisms: 1) insertional mutagenesis and 2) non-allelic homologous recombination. The only known neutrophil function affected by retrotransposition is that of NADPH oxidase activity. Four patients with chronic granulomatous disease (CGD) are known with LINE-1-mediated insertional inactivation of CYBB, the gene that encodes the gp91 component of the phagocyte NADPH oxidase. In addition, five CGD patients had a large deletion in the NCF2 gene, encoding the p67 component, and two CGD patients had a similar deletion in NCF1, encoding p47 . These deletions were caused by non-allelic homologous recombination between two Alu elements at the borders of each deletion. Alu elements have spread throughout the human genome by LINE-1 retrotransposition. Probably, the occurrence of LINE-1-mediated insertions causing autosomal CGD has been underestimated. It might be worthwhile to reinvestigate the DNA from autosomal CGD patients with missplice mutations and large deletions for indications of LINE-1-mediated insertions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.