Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting
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 polici...
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doaj-7572c88aa88540a38f14bb0c761588882020-11-25T01:46:22ZengMDPI AGGenes2073-44252020-09-01111140114010.3390/genes11101140Pathogenic Variant Filtering for Mitochondrial Genome Haplotype ReportingCharla Marshall0Kimberly Sturk-Andreaggi1Joseph D. Ring2Arne Dür3Walther Parson4Armed Forces Medical Examiner System’s Armed Forces DNA Identification Laboratory (AFMES-AFDIL), Dover Air Force Base, DE 19902, USAArmed Forces Medical Examiner System’s Armed Forces DNA Identification Laboratory (AFMES-AFDIL), Dover Air Force Base, DE 19902, USAArmed Forces Medical Examiner System’s Armed Forces DNA Identification Laboratory (AFMES-AFDIL), Dover Air Force Base, DE 19902, USAInstitute of Mathematics, University of Innsbruck, 6020 Innsbruck, AustriaForensic Science Program, The Pennsylvania State University, University Park, PA 16802, USAGiven 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.https://www.mdpi.com/2073-4425/11/10/1140mitochondrial genomemitochondrial DNAcoding regionvariant filteringpathogenic variantshaplotype |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Charla Marshall Kimberly Sturk-Andreaggi Joseph D. Ring Arne Dür Walther Parson |
spellingShingle |
Charla Marshall Kimberly Sturk-Andreaggi Joseph D. Ring Arne Dür Walther Parson Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting Genes mitochondrial genome mitochondrial DNA coding region variant filtering pathogenic variants haplotype |
author_facet |
Charla Marshall Kimberly Sturk-Andreaggi Joseph D. Ring Arne Dür Walther Parson |
author_sort |
Charla Marshall |
title |
Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting |
title_short |
Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting |
title_full |
Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting |
title_fullStr |
Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting |
title_full_unstemmed |
Pathogenic Variant Filtering for Mitochondrial Genome Haplotype Reporting |
title_sort |
pathogenic variant filtering for mitochondrial genome haplotype reporting |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2020-09-01 |
description |
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. |
topic |
mitochondrial genome mitochondrial DNA coding region variant filtering pathogenic variants haplotype |
url |
https://www.mdpi.com/2073-4425/11/10/1140 |
work_keys_str_mv |
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