The Impact of Sequencing Human Genome on Mitochondrial Disorder
A Hameed Khan
ABSTRACT
The purpose of this abstract is to study inherited mitochondrial diseases (MD) for which effective treatments do not exist. The purpose of Sequencing Human Genome is to Diagnose a mutated gene and then Prevent and Treat a disease. The fact that the majority of pathogenic mutations are found in coding regions; the coding gene regions, the ‘exome’, comprise approximately 1.6% of the human genome. The fastest way to identify a disease-causing mutation is from the exome sequencing alone. Our body carries two genomes, a human genome and a mitochondrial genome. While our genome is located on liner chromosomes, Mitochondrial genome has the circular chromosome found inside the cellular organelle. Located in the cytoplasm, mitochondria are the site of the cell’s energy production and other metabolic functions. Mitochondrial diseases are caused by pathogenic mutations that directly affect the energy metabolism that takes place inside mitochondria in the process of Oxidative Phosphorylation (OXPHOS). It involves large respiratory chain (RC) enzyme complexes, and hence are known collectively as RC diseases. Sequencing is the best diagnostic technique and it helps us identifying the mutation responsible for causing the disease. Once the serious mitochondrial disorder is confirmed by sequencing, it is the parents not the authority who decide if the fetus survives or not. If the parents decide to keep the child alive, the next step is either to have three-parent children or to develop treatments of the disorder either by gene therapy or by drug therapy. Compare to human genome, Mitochondrial genome is very small. By making AZQ (US Patent 4,233,215), I have demonstrated how to design drugs to shut off genes responsible for causing Glioblastoma, the brain cancer. It is the challenge for the next generation of scientists (my students) to activate the prodrug moieties like Aziridine and Carbamate to shut off acid producing Latic Acidosis mitochondrial genes without attacking the normal mitochondria.
