Retrotransposable genetic elements causing neutrophil defects

Background 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 IN terspersed Element‐1 ( LINE ‐1) family. LINE ‐1s may cause gene inactivation and human disease. Design We present a brief summary of the published knowledge about LINE ‐1s in humans and the RNA s that these elements can transpose, and we focus on the effect of LINE ‐1‐mediated retrotransposition on human neutrophil function. Results Retrotransposons can cause genetic disease by two primary mechanisms: (1) insertional mutagenesis and (2) nonallelic 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 phox component of the phagocyte NADPH oxidase. In addition, 5 CGD patients had a large deletion in the NCF 2 gene, encoding the p67 phox component, and 2 CGD patients had a similar deletion in NCF 1 , encoding p47 phox . These deletions were caused by nonallelic homologous recombination between 2 Alu elements at the borders of each deletion. Alu elements have spread throughout the human genome by LINE ‐1 retrotransposition. Conclusions 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.