Computational and Experimental Approaches For Evaluating the Genetic Basis of Mitochondrial Disorders
Contributors: Mootha, Vamsi K.; Springer, Michael; Walsh, Christopher A.; Korson, Mark S.; Hirschorn, Joel N.; Church, George M.; Ruvkun, Gary
Published: 2013
Language: eng
Description: Mitochondria are responsible for many fundamental biological pathways and metabolic processes, including aerobic ATP production by the mitochondrial respiratory chain. In humans, mitochondrial dysfunction can lead to severe disorders of energy metabolism, which are collectively referred to as mitochondrial disorders and affect approximately 1:5,000 individuals. These disorders are clinically heterogeneous and can affect multiple organ systems, often within a single individual. Symptoms can include myopathy, exercise intolerance, hearing loss, blindness, stroke, seizures, diabetes, and GI dysmotility. Mutations in over 150 genes in the mitochondrial DNA (mtDNA) and nuclear genome are known to cause mitochondrial diseases and an additional ~1,000 nuclear-encoded mitochondrial proteins have the potential to underlie mitochondrial disorders but have not yet been linked to human disease. As a result, determining a molecular diagnosis for patients with suspected mitochondrial disorders remains a challenge.
Notes: Keywords: Exome sequencing, Genomics, Mendelian disorders, Mitochondria, Mitochondrial disorders, Systems biology.

Thesis Ph.D. Harvard University 2013