A sensitive denaturing gradient-gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region

A population study of heteroplasmy in the hypervariable region 1 (HV1) port ion of the human mtDNA control region was performed. Blood samples from 253 randomly chosen individuals were examined using a sensitive denaturing gra dient-gel electrophoresis (DGGE) system, This method is capable of detectin g heteroplasmic proportions as low as 1% and virtually all heteroplasmy whe re the minor component is greater than or equal to 5%. Heteroplasmy was obs erved in 35 individuals (13.8%; 95% confidence interval [CI] 9.6-18.0). Of these individuals, 33 were heteroplasmic at one nucleotide position, wherea s 2 were heteroplasmic at two different positions (a condition known as "tr iplasmy"), Although heteroplasmy occurred at a total of 16 different positi ons throughout HV1, it was most frequently observed at positions 16093 (n = 13) and 16129 (n = 6), In addition, the majority of heteroplasmic variants occurred at low proportions and could not be detected by direct sequencing of PCR products. This study indicates that low-level heteroplasmy in HV1 i s relatively common and that it occurs at a broad spectrum of sites. Our re sults corroborate those of other recent reports indicating that heteroplasm y in the control region is more common than was previously believed-a findi ng that is of potential importance to evolutionary studies and forensic app lications that are based on mtDNA variation.