A family exhibiting heteroplasmy in the human mitochondrial DNA control region reveals both somatic mosaicism and pronounced segregation of mitotypes

Abstract

A family exhibiting heteroplasmy at position 16355 in hypervariable region I of the human mtDNA control region has been identified. This family consists of a mother, daughter, and son. DNA samples extracted from blood stains, buccal swabs, and hairs from these individuals were amplified by PCR and sequenced utilizing fluoresence-labeled dye terminator chemistry in an automated DNA sequencer. In both the daughter and mother, heteroplasmy was observed in DNA extracted from blood stains, buccal swabs, and hairs. In the blood stains, the proportion of cytosine was greater than thymine in both individuals. Buccal swab extracts showed a more balanced contribution from the two nucleotides. Telogenic hair root and hair shaft samples exhibited a wide range of nucleotide contributions at this position, from predominately cytosine in some samples to predominately thymine in others. The apparent stochastic segregation of mitotypes in hair samples is discussed from a forensic viewpoint, and the mechanism of mtDNA heteroplasmy is considered.

Marked mitochondrial DNA sequence heterogeneity in single CD34+ cell clones from normal adult bone marrow

“…22 Multiple mtDNA genotypes were present in closely proximate hair follicles; while individual cells were not analyzed, the interpretation of the investigators was that mtDNA mutations occur with aging and resolve to homoplasmy within cells. 23,24 Primary tissue and cell lines of colon tumor origin also show a high frequency of mtDNA mutations, presumably due to fixation of established homoplasmic nucleotide changes. 25 More generally, our results are concordant with observations of surprisingly rapid divergence and resolution to homoplasmy of mtDNA sequence among inbred Holstein cows 26 and in carefully studied human kindreds.…”

MtDNA Sequence Analysis Using Capillary Electrophoresis and Its Application to the Analysis of MtDNA in Hair.

“…Length heteroplasmy has been reported within one individual 18,22,23) , and variable proportions of heteroplasmy have also been observed in hair roots within a single individual 24,25) . Our study also indicates variations in the proportions of heteroplasmy, which were observed in hairs, nails and saliva from a single individual.…”

Mitochondrial DNA Heteroplasmy Among Hairs from Single Individuals

“…Heteroplasmy in the control region was initially not considered to be significant (2), but it now appears to be a more frequent phenomenon than had originally been thought (3-6). Inter-and intra-generational heteroplasmy has been reported and the proportion of heteroplasmy appears to vary among different family members (5,7,8). Intra-individual heteroplasmy has also been reported in several studies (9,10).…”

“…Length heteroplasmy in the HV1 and HV2 region, near nucleotide positions 16189 and 309-315, was found among hairs within a single individual (11,12) and the mechanism involved in this length heteroplasmy has been investigated (13,14). Site heteroplasmy, at a single nucleotide position in the control region of mtDNA in hairs, has also been reported and its proportions varied among hairs within a single individual (5,15). The frequency of site heteroplasmy among hairs from an individual with a homoplasmic blood sample has also been reported (16,17).…”