Role of Mitochondrial Genetics in Complex Diseases

The study of genetic disease is often centered on the human nuclear genome consisting of ~3.1 billion nucleotides and 25,000–30,000 genes located on the 23 pairs of chromosomes, whereas the mitochondrial genome has received less attention. Each cell contains numerous mitochondria and each mitochondrion contains several copies of mitochondrial DNA (mtDNA). Thus, a cell contains several thousand copies of mitochondrial genome. The mitochondrial genome is a short, circular genome with 16,569 nucleotides and 37 genes (Fig. 1) encoding 13 proteins, 22 tRNAs, and 2 rRNAs, and gene density of 1 per 450 bp. Introns are absent in mtDNA and coding DNA constitutes 93% of mtDNA in contrast to ~3% in nuclear DNA. Mitochondria play a critical role in energy metabolism and Reactive Oxygen Species (ROS) production, and mutations in mtDNA are risk factors for various complex disorders. Thus, mutations of