AGBT talk: Kateryna Makova, Penn State Univerisity

Title: Dynamics of Mitochondrial Heteroplasmy in three families

Brief overview of Mt DNA:  37 genes, 16.5kb long.  Maternally transmitted, sperm MT is destroyed upon fertilization, and also a high mutation rate (poor repair mechanism, environmental effects.)

Heteroplasmy: presence of more than one mtDNA variant in an individual.

Mitochondrial bottleneck during oogenesis.

Makes MT DNA interesting.

more than 200 diseases are mutations in mtDNA.  Can be severe, frequency of disease/normal mtDNA in one person can determine severity.  There is no cure – so focus is on prevention of transmission.  (Nuclear transfer of maternal DNA into a n enucleated oocite of a healthy female could be done… but hasn’t been proved.)

mtDNA mutations are predisposing to features of aging. (alzheimers, parkinsons, diabetes, etc). Also possible link to autism.

mtDNA mutations are also markers for cancer – link not yet determined.

Recent studies with NGS get you further indetecting heteroplasmy, but outstanding dissagreements. (He at al, 2010 : heteroplasmy is common (from cell lines), Li et al, 2010: heteroplasmy is rare (from 131 individuals.))

question: how does heteroplasmy affect individuals, and how does it change during transmission to offspring?

Study design [not blogging this part – go read the research. (-: ]

Real challenge: how to distinguish low freq heteroplasmy from seq errors?  Tackled with lots of simulations and clonal samples and spike ins. Result: 2% or greater (conservatively, probably closer to 1%).


6 heteroplasmic sites – [nice map of chrMT, but um… yeah, not bloggable without a camera.]

“Static heteroplasmy” never observed.  Frequency shift without mutation, somatic (shifts in minor allele frequency between tissues) and germline (passed on to child) mutations observed.

Found: One germline, 3 frequency shits, 2 somatic mutations.

The one germline was different between two children from one mother, suggested that mutation happened early on.

Use Galaxy for this project.  History and log are available for this project – can be run on the cloud if you like. [cool.]


  • Heteroplasmic frequency shifts happen frequently,
  • analysis is reproducible,
  • objective determination frequency threshold calculations,
  • and a framework exists for repeating this work.

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