Mitochondrial DNA analysis and typing
Mitochondrial DNA (mtDNA) analysis and typing is a specialized form of DNA analysis that examines the genetic material found within mitochondria, the energy-producing organelles in cells. This technique is particularly valuable in forensic contexts where traditional DNA methods may fail due to the degradation of biological samples, such as hair, teeth, bones, and nails. Mitochondrial DNA consists of a circular genome that includes genes critical for mitochondrial function as well as a control region that allows for the accumulation of mutations over generations. These mutations are analyzed in two hypervariable regions known as HV1 and HV2, which provide a means for identifying genetic differences among individuals.
While mtDNA analysis does not offer the same level of discrimination as nuclear DNA analysis, it is often the only viable option in challenging cases. Importantly, mtDNA is inherited maternally, meaning that maternal relatives, including siblings, share the same mtDNA haplotype. This characteristic makes mtDNA analysis a powerful tool for identifying individuals, particularly in forensic investigations involving unidentified remains. Historical cases, such as the identification of U.S. service members and royal family members, have underscored the significance of mtDNA analysis in resolving mysteries of the past. Overall, mitochondrial DNA typing serves as an essential resource in both forensic science and historical research.
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Mitochondrial DNA analysis and typing
DEFINITION: Form of DNA typing in which the genetic material found inside cellular mitochondria is analyzed.
SIGNIFICANCE: Mitochondrial DNA analysis is often used when traditional DNA typing methods are unsuccessful because of biological degradation. The technique is employed in cases involving hair, teeth, skeletal remains, and other difficult forensic samples. It has also been used to identify missing persons and the victims of mass disasters.
Mitochondria are cellular organelles responsible for bodily energy production. Human mitochondria contain a circular genome of 16,569 bases, the bulk of which encodes thirty-seven RNA (ribonucleic acid)/proteins. The remaining segment, termed the control region, regulates (deoxyribonucleic acid) replication and transcription.
The noncoding nature of the control region has allowed mutations (or polymorphisms) to accumulate over time, most of which are located in two hypervariable regions: HV1 and HV2. Scientists conduct mitochondrial DNA (mtDNA) typing by obtaining the HV DNA sequences and comparing them with the reference sequence known as the Anderson sequence or the Cambridge Reference Sequence. Differences between the sample mtDNA and the reference sequence are reported based on the type of polymorphism (base change, insertion/deletion) and its nucleotide position. For instance, if mtDNA from a hair has a C at position 152 while the reference sequence has a T, the DNA type (termed a haplotype) for that individual would be reported as 152C. Any other polymorphisms are reported as well, and the frequency of that haplotype in humans can be determined.
MtDNA typing does not have the discriminatory power of nuclear DNA analysis; however, there are instances in which mtDNA is the only DNA recoverable, particularly from materials of forensic interest. This can be the case for shed hair, aged bone or teeth, nails, and mummified tissue, among others. Nuclear DNA contained in such samples may be degraded, whereas mtDNA, owing to its high copy number (hundreds or thousands of copies per cell) and protection afforded by the mitochondrion, is still analyzable.
Another key feature of mtDNA is that it is maternally inherited, with all mitochondria stemming from the egg. As a result, siblings and other maternal relatives share the same mtDNA haplotype. This feature has made mtDNA typing an invaluable tool in forensic science. The Armed Forces DNA Identification Laboratory uses mtDNA to identify skeletal remains recovered from war casualties by comparing mtDNA samples from potential relatives. The Federal Bureau of Investigation (FBI) operates laboratories that focus solely on mtDNA analysis.
Several historical mysteries have been resolved using mtDNA. In 1998, mtDNA analysis was used to identify the remains of the Vietnam War service person interred in the Tomb of the Unknowns at Arlington National Cemetery as US Air Force First Lieutenant Michael Blassie. Similarly, mtDNA aided in the identification of the members of the Romanov family, the last Russian royal family, who were murdered during the Bolshevik Revolution in 1918.
Bibliography
Butler, John M. Forensic DNA Typing: Biology, Technology, and Genetics of STR Markers. 2d ed. Burlington, Mass.: Elsevier Academic Press, 2005.
Cox, Margaret, et al. The Scientific Investigation of Mass Graves. New York: Cambridge University Press, 2008.
Hummel, Susanne. Ancient DNA Typing: Methods, Strategies, and Applications. New York: Springer, 2002.
Vinueza-Espinosa, Diana C. "Mitochondrial DNA Control Region Typing from Highly Degraded Skeletal Remains by Single-Multiplex Next-Generation Sequencing." Electrophoresis, vol. 44, no. 17-18, Sept. 2023, pp. 1423-1434, doi.org/10.1002/elps.202200052. Accessed 15 Aug. 2024.