05050
Detection of Low Levels of Mitochondrial DNA Mutations in Diabetic Patients
Author: Richard Jimenez
Mentor: Dr. Vincent Procaccio
Mitochondria are organelles that produce essential energy for cell function, often referred to as the
‘powerhouses of the cell’ (Wallace, et al., 2002). Each mitochondrion contains multiple copies of a small
circular piece of DNA called the mitochondrial DNA (mtDNA) that code important proteins needed for
energy production. This mtDNA is only inherited from the mother and is able to mutate, changing the
genetic information. Mitochondrial mutations cause many known mitochondrial diseases, and a diagnosis is
usually made from a muscle biopsy. For example, a common mtDNA mutation at position 3243 is present in
the cell at different levels from a few percent to 100% mutant and causes diabetes at low levels of mutation
and severe neurological diseases at higher levels. Conventional techniques used to detect this 3243 mutation
often overlook the presence of the mutation at very low levels, and we sought to develop an alternative
technique that improves the detection sensitivity and throughput of mtDNA mutations. To test the sensitivity
of our new mutation detection method, we analyzed diabetic patients’ blood samples that may possibly carry
the mutation. We found that several patients carry the 3243 mutation while conventional techniques missed
the presence of the mutation in the blood samples. This study suggests that our more sensitive technique can
accurately diagnose a carrier of a mtDNA mutation without the use of a painful muscle biopsy. In addition,
the use of our technique may help redefine the frequency or prevalence of the 3243 mutation in the diabetic
population.