The human mitochondrial genome consists of a multicopy, circular dsDNA molecule 
of 16,569 base pairs. It encodes for 13 proteins, two ribosomal genes, and 22 
tRNAs that are essential in the generation of cellular ATP by oxidative 
phosphorylation in eukaryotic cells. Germline mutations in mitochondrial DNA 
(mtDNA) are an important cause of maternally inherited diseases, while somatic 
mtDNA mutations may play important roles in aging and cancer. mtDNA 
polymorphisms are also widely used in population and forensic genetics. 
Therefore, methods that allow the rapid, inexpensive and accurate sequencing of 
mtDNA are of great interest. One such method is the Affymetrix GeneChip Human 
Mitochondrial Resequencing Array 2.0 (MitoChip v.2.0) (Santa Clara, CA). A 
direct comparison of 93 worldwide mitochondrial genomes sequenced by both the 
MitoChip and dideoxy terminator sequencing revealed an average call rate of 
99.48% and an accuracy of > or =99.98% for the MitoChip. The good performance 
was achieved by using in-house software for the automated analysis of additional 
probes on the array that cover the most common haplotypes in the hypervariable 
regions (HVR). Failure to call a base was associated mostly with the presence of 
either a run of > or =4 C bases or a sequence variant within 12 bases up- or 
downstream of that base. A major drawback of the MitoChip is its inability to 
detect insertions/deletions and its low sensitivity and specificity in the 
detection of heteroplasmy. However, the vast majority of haplogroup defining 
polymorphism in the mtDNA phylogeny could be called unambiguously and more 
rapidly than with conventional sequencing.