Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting.

Charla Marshall,Walther Parson,Arne Dür,Kimberly Sturk-Andreaggi,Joseph D Ring

doi:10.3390/genes11101140

Charla Marshall, Walther Parson + Show 3 more

Open Access

https://doi.org/10.3390/genes11101140

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Abstract

Given the enhanced discriminatory power of the mitochondrial DNA (mtDNA) genome (mitogenome) over the commonly sequenced control region (CR) portion, the scientific merit of mitogenome sequencing is generally accepted. However, many laboratories remain beholden to CR sequencing due to privacy policies and legal requirements restricting the use of disease information or coding region (codR) information. In this report, we present an approach to obviate the reporting of sensitive codR data in forensic haplotypes. We consulted the MitoMap database to identify 92 mtDNA codR variants with confirmed pathogenicity. We determined the frequencies of these pathogenic variants in literature-quality and forensic-quality databases to be very low, at 1.2% and 0.36%, respectively. The observed effect of pathogenic variant filtering on random match statistics in 2488 forensic-quality mitogenome haplotypes from four populations was nil. We propose that pathogenic variant filtering should be incorporated into variant calling algorithms for mitogenome haplotype reporting to maximize the discriminatory power of the locus while minimizing the reveal of sensitive genetic information.

Highlights

The field of forensic genetics is poised to adopt complete mitochondrial genome sequencing for use in routine casework
Many laboratories remain beholden to control region (CR) sequencing until the use of the entire mitogenome can be accepted in court, as the affiliated legal system(s) in some jurisdictions prohibit coding region DNA evidence, as it may reveal sensitive genetic information about the DNA donor
Since mitogenome sequencing and the forensic reporting of mitochondrial DNA (mtDNA) haplotypes may reveal disease-related information contained within the coding region (codR) that may encroach upon privacy rights and is generally not needed for forensic identification, pathogenic alleles can be filtered in order to obviate the reporting of sensitive codR information

Summary

Introduction

The field of forensic genetics is poised to adopt complete mitochondrial genome (mitogenome) sequencing for use in routine casework. Many laboratories remain beholden to CR sequencing until the use of the entire mitogenome can be accepted in court, as the affiliated legal system(s) in some jurisdictions prohibit coding region (codR) DNA evidence, as it may reveal sensitive genetic information about the DNA donor. There are several diseases associated with these pathogenic variants, including LHON (Leber hereditary optic neuropathy), MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and Leigh disease [8]. Even more diseases, such as endometriosis, cyclic vomiting syndrome, and many others, have been shown to be potentially correlated with mtDNA sequence variants, but the causative links are lacking. Since mitogenome sequencing and the forensic reporting of mtDNA haplotypes may reveal disease-related information contained within the codR that may encroach upon privacy rights and is generally not needed for forensic identification, pathogenic alleles can be filtered in order to obviate the reporting of sensitive codR information

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