The authors then carry out a second round of fusions, but in these cells, they have had the mitochondrial DNA removed. Here, if the fused cells are no longer defective, the mutation is in the patient's nuclear DNA. If the fusions remain defective, the causal mutation is likely to be in the mitochondrial DNA. This technique is a very rapid and powerful means to categorize the mutation type of cells from different patients. The authors effectively demonstrated the strength of this technique using cells from 10 different patients, and showed that 7 contained nuclear mutations and 1 contained a mitochondrial mutation. The authors then focused on two patients whose cells did not complement one another, meaning the same gene was mutated. From there they used a battery of mapping, microarray and bioinformatics analyses and identified mutations for both patients in the NDUFS6 gene; a gene not previously shown to be involved in this type of disease. This work shows how combining a series of analyses, including genetic, biochemical, microarray, and bioinformatics techniques provide a rapid and effective means to pinpoint mutations in diseases that have complex genetic backgrounds.
An accompanying commentary by Eric Schon provides an overview of the complexity of the mitochondrial respiratory chain/oxidative phosphorylation system and a detailed discussion of the techniques used in this paper. TITLE: NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency
AUTHOR CONTACT:
David R. Thorburn
Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Rd, Parkville, Victoria 3052, Australia
Phone: 613-8341-6235; Fax: 613-8341-6212; E-mail: david.thorburn@mcri.edu.au
View the PDF of this article at: http://www.jci.org/cgi/content/full/114/6/837
AUTHOR CONTACT:
Eric A. Schon
Columbia University, 630 West 168th St. New York, NY 10032, USA
Phone: 212-305-1665; Fax: 212-305-3986; E-mail: eas3@columbia.edu
Journal
Journal of Clinical Investigation