The use of mtDNA as a forensic tool evolved from its role in the study of human history and human disease. mtDNA analysis solved several historical mysteries, such as the identification of the Czar's remains in Russia and the skeleton of Jesse James. Anthropologists have recovered mtDNA from Neanderthal skeletons at least 30,000 years old.

This type of forensic analysis routinely aids in identification of war dead, including a serviceman who served in Vietnam now buried in the Tomb of the Unknown Soldier. Recently, it augmented STR testing of remains from the World Trade Center attacks (9/11/01).

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