Heteroplasmy and Forensic Mitochondrial DNA Testing

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Heteroplasmy and Forensic Mitochondrial DNA
Testing

• By Marc Cary

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Why Test Mitochondrial DNA?

• 1,000 10,000 copies per cell
• Only 16,569 bp
• Small sample size needed
• Badly degraded samples work

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Sources of mtDNA

• Hair
• Blood
• Muscle tissue
• Skin

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What is Heteroplasmy?

• Random mutations that occur in mtDNA
• Up to 6 mutations in some individuals
• Leads to different versions of mtDNA in an
  individual
• Once thought to be extremely rare

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Causes of Heteroplasmy

• Molecular events not quite understood
• Most probable explanation mutations in female
  germ line followed by subsequent differentiation
  during embryonic development (Table 1)
• HVI and HVII (Hypervariable sequences) are
  typically analyzed for forensic use
• Hotspots are prone to heteroplasmy (Table 1)

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Causes of Heteroplasmy
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Detection of Heteroplasmy

• Detection depends upon procedure used to analyze
  mtDNA
• Standardization is needed for mtDNA typing
  procedures.

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Heteroplasmy and Human Hair

• Human hair has high frequency of heteroplasmy
  (stem cell formation)
• Example hair from same individual may have
  different mtDNA
• Although hair contains heteroplasmy, other
  tissues from same individual may not ie. blood,
  muscle, skin

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Heteroplasmy complicates forensic mtDNA testing

• May not always be detected depending on the
  tissue type and analysis procedure
• May be difficult to form a basis of exclusion
• In case of non-mutation, sequence frequency is
  determined form an mtDNA database

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Heteroplasmy Benefits Forensic mtDNA Testing

• Rarity of a particular heteroplasmy may increase
  discriminating power

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Take Home Messages

• An Individual may have different versions of
  mtDNA
• Heteroplasmy may complicate mtDNA testing, but
  may also make it more efficient
• Tissue type is important when analyzing mtDNA
• Standardization is needed in mtDNA testing
  procedures

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References

• T. Grzybowski, Extremely high levels of human
  mitochondrial DNA heteroplasmy in single hair
  roots, Electrophoresis 21 (2000) 548-553
• P. DEustachio, High levels of mitochondrial DNA
  in human hairs by Budowle et al., Forensic
  Science International 130 (2002) 63-67
• W. Shields, SUNY-Syracuse