Biochemical and Biophysical Research Communications
Mitochondrial ND5 mutations in idiopathic Parkinson’s disease
Section snippets
Methods
Methods employed in this study were as previously described [9]. Genomic DNA was extracted from frontal lobe tissue from 8 idiopathic PD samples and 8 similarly aged controls (PD mean age, 78; control mean age, 74; ns). The region of interest in ND5 was PCR amplified and 96 independent clones from each sample were then cycle sequenced. Sequencer data were aligned against the wildtype sequence (Sequencher, Gene Codes) and all potential mutations were operator verified. Usable sequence data were
Results
Results of the present study are summarized and compared with the results of the previous study over this region (Table 1) [9]. Fifteen of 16 samples studied were correctly identified as either PD or control on the basis of the presence or absence of amino acid changing mutations in the specific regions studied. A single control was misidentified as PD. Whether or not this individual would have developed Parkinson’s disease later in life is unknowable. In several instances we identified
Discussion
Our initial broad-ranging and in-depth study of heteroplasmic mtDNA mutations in idiopathic PD suggested on retrospective analysis that a small region ND5 and to a lesser extent a small region in ND2 harbor mutations segregating PD from controls. The present prospective study appears to confirm that observation with respect to ND5. Both studies identified relevant heteroplasmic mutations but at frequencies well below that previously associated with disease causing mutations. The catalytic
Acknowledgments
This work was supported by the Dana Foundation and by a Morris K. Udall Parkinson’s Disease Center of Excellence grant from NINDS. We are grateful to Dr. Ted Dawson and colleagues, Dr. Ronald Hamilton, and Dr. Ali Rajput for tissue samples.
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