title: A sensitive denaturing gradient-Gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region.
abstract: A population study of heteroplasmy in the hypervariable region 1 (HV1) portion of the human mtDNA control region was performed. Blood samples from 253 randomly chosen individuals were examined using a sensitive denaturing gradient-gel electrophoresis (DGGE) system. This method is capable of detecting heteroplasmic proportions as low as 1% and virtually all heteroplasmy where the minor component is > or = 5%. Heteroplasmy was observed in 35 individuals (13.8%; 95% confidence interval [CI] 9.6-18.0). Of these individuals, 33 were heteroplasmic at one nucleotide position, whereas 2 were heteroplasmic at two different positions (a condition known as "triplasmy"). Although heteroplasmy occurred at a total of 16 different positions 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 is relatively common and that it occurs at a broad spectrum of sites. Our results corroborate those of other recent reports indicating that heteroplasmy in the control region is more common than was previously believed-a finding that is of potential importance to evolutionary studies and forensic applications that are based on mtDNA variation.
authors.affiliation: University of Maryland, School of Medicine, Division of Human Genetics, Baltimore, MD, USA. lois.tully@gte.net
authors.forename: L A
authors.initials: LA
authors.lastname: Tully
authors.forename: T J
authors.initials: TJ
authors.lastname: Parsons
authors.forename: R J
authors.initials: RJ
authors.lastname: Steighner
authors.forename: M M
authors.initials: MM
authors.lastname: Holland
authors.forename: M A
authors.initials: MA
authors.lastname: Marino
authors.forename: V L
authors.initials: VL
authors.lastname: Prenger
mesh_terms: D001483:Base Sequence; D003593:Cytoplasm / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005006:Ethnicity / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D016018:Least-Squares Analysis; D008928:Mitochondria / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009691:Nucleic Acid Denaturation / Q000235:genetics; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D004272:DNA, Mitochondrial; D009692:Nucleic Acid Heteroduplexes