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

Genes
Mitchell M HollandJennifer A McElhoe

Abstract

Abstract : Distinguishing between maternal relatives through mitochondrial (mt) DNA sequence analysis has been a longstanding desire of the forensic community. Using a deep-coverage, massively parallel sequencing (DCMPS) approach, we studied 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 observed on a frequent basis in these closely related maternal relatives, with the minor variant often presented as 2-10% of the sequencing reads. A total of 17 pairs exhibited differentiating heteroplasmy (44%), with the majority of sites (76%, 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%), with no duplicate sites of either differentiating or shared heteroplasmy observed; a single nucleotide p...Continue Reading

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Citations

Jul 31, 2018·Electrophoresis·Vania PereiraClaus Børsting
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Methods Mentioned

BETA
PCR
electrophoresis

Software Mentioned

GM HTS
RStudio
MiSeq Reporter
Phylotree
Unix shell Bash
Genome Analysis ToolKit ( GATK )
MiSeq
HTS
STS
Terminal

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