MtDNA substitution rate and segregation of heteroplasmy in coding and noncoding regions

Abstract

The mitochondrial DNA (mtDNA) substitution rate and segregation of heteroplasmy were studied for the non-coding control region (D-loop) and 500 bp of the coding region between nucleotide positions 5550 and 6050, by sequence analysis of blood samples from 194 individuals, representing 33 maternal lineages. No homoplasmic nucleotide substitutions were detected in a total of 292 transmissions. The estimated substitution rate per nucleotide per million years for the control region (micro>0.21, 95% CI 0-0.6) was not significantly different from that for the coding region (micro>0.54, 95% CI 0-1.0). Variation in the length of homopolymeric C streches was observed at three sites in the control region (positions 65, 309 and 16,189), all of which were in the heteroplasmic state. Segregation of heteroplasmic genotypes between generations was observed in several maternal pedigrees. At position 309, a longer poly C tract length was strongly associated with a higher probability for heteroplasmy and rapid segregation between generations. The length heteroplasmy at positions 65 and 16,189 was found at low frequency and was confined to a few families.

Mosaicism for mitochondrial DNA polymorphic variants in placenta has implications for the feasibility of prenatal diagnosis in mtDNA diseases

“…Similarly, (P2) placenta from a 7-week termination of pregnancy was heteroplasmic for C insertion polymorphisms within the homopolymeric C tract (ie the run of C residues between 303 and 315 bp). This generates nested heteroplasmic length variants 20 ( Figure length variants in all regions ( Figure 2a, panel 2). The variation may be more marked in the term placenta than in the 7-week placenta (coefficients of variation 0.27 -0.51 and 0.07 -0.18, respectively), although this could be because the polymorphisms were different in the two cases.…”

Mitochondrial DNA mutations in human tumor cells

“…mtDNA mutations that arise in the female germ line are transmitted to the next generation, where they are observed as new mtDNA polymorphisms or as pathogenic mtDNA mutations (6). mtDNA mutations also occur in somatic cells.…”

Forensic DNA profiling: state of the art

“…mtDNA exists in a much higher copy number in the cell compared with nuclear DNA and is more likely to produce a result. 31,32 Mitochondrial DNA is inherited down the maternal line and is particularly useful in cases of missing persons when maternal relatives separated by several generations can act as reference samples. It has also been used to identify the skeletal remains of war casualties 33,34 and in the identification of the remains of Tzar Nicholas II of Russia.…”