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Deep-Coverage MPS Analysis of Heteroplasmic Variants Within the mtGenome Allows for Frequent Differentiation of Maternal Relatives

NCJ Number
Genes Volume: 9 Issue: 3 Dated: 2018
Date Published
5 pages
Since distinguishing between maternal relatives through mitochondrial (mt) DNA sequence analysis has been a longstanding desire of the forensic community, the current study used a deep-coverage, massively parallel sequencing (DCMPS) approach to study the pattern of mtDNA heteroplasmy across the mtgenomes of 39 mother-child pairs of European decent: haplogroups H, J, K, R, T, U, and X.

Both shared and differentiating heteroplasmy were frequently observed in these closely related maternal relatives, with the minor variant often presented as 2-10 percent of the sequencing reads. A total of 17 pairs exhibited differentiating heteroplasmy (44 percent), with the majority of sites (76 percent, 16 of 21) occurring in the coding region, further illustrating the value of conducting sequence analysis on the entire mtgenome. A number of the sites of differentiating heteroplasmy resulted in non-synonymous changes in protein sequence (5 of 21), and to changes in transfer or ribosomal RNA sequences (5 of 21), highlighting the potentially deleterious nature of these heteroplasmic states. Shared heteroplasmy was observed in 12 of the 39 mother-child pairs (31 percent), with no duplicate sites of either differentiating or shared heteroplasmy observed; a single nucleotide position (16093) was duplicated between the data sets. Finally, rates of heteroplasmy in blood and buccal cells were compared, since it is known that rates can vary across tissue types, with similar observations in the current study. Study data support the view that differentiating heteroplasmy across the mtgenome can be used to frequently distinguish maternal relatives, and could be of interest to both the medical genetics and forensic communities. (publisher abstract modified)

Date Published: January 1, 2018