Facilitating complex DNA mixture interpretation by sequencing highly polymorphic haplotypes

Voskoboinik, Lev; Motro, Uzi; Darvasi, Ariel

doi:10.1016/j.fsigen.2018.05.001

Cited by 33 publications

(25 citation statements)

References 17 publications

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“…Altogether, 60 MH candidates were primarily screened out from ALFRED database (Allele Frequency Database, Yale University) and previous published literatures (Supporting Information ). Altogether, there were 46 3‐SNPs, 13 4‐SNPs, and 1 5‐SNPs MHs in the candidate panel, spreading across 21 human autosomes.…”

Section: Resultsmentioning

confidence: 99%

A microhap panel for kinship analysis through massively parallel sequencing technology

Lin

Gao

et al. 2019

Electrophoresis

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A microhap panel for kinship analysis through massively parallel sequencing technologyIt is widely recognized that microhaps are powerful markers for different forensic purposes, mainly due to their advantages of both short tandem repeats and single nucleotide polymorphisms, including multiple alleles, low mutation rate, and absence of stutter peaks. In the present study, a panel of 60 microhap loci was developed and utilized in forensic kinship analysis as a preliminary study. Genotyping of microhap was performed by massively parallel sequencing and haplotypes were directly achieved from sequence reads of 73 samples from Chinese Han population. We observed that 49 out of 60 loci have effective number of alleles greater than 3.0 and 10 out of 60 have values above 4.0, with an average value of 3.5598. The heterozygosity values were in a range from 0.5840 to 0.8546 with an average of 0.7268 and the cumulative power of exclusion value of the 60 loci is equal to 1-4.78 × 10 −18 . Moreover, we demonstrated the applicability of this method by different relationship inference problems, including identification of single parent-offspring, full-sibling, and second-degree relative. The results indicated that the assembled microhap panel provided more power for relationship inference, than commonly used short tandem repeats or single nucleotide polymorphism system.Abbreviations: Ae, effective number of alleles; LR, likelihood ratio; MH, microhap; MPS, massively parallel sequencing; PD, power of discriminative; PE, power of exclusion; PIC, polymorphism information content; ROI, region of interest; TPI, typical paternity index * These authors contributed equally to this work.Color online: See the article online to view Figs. 1-6 in color.

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Section: Resultsmentioning

confidence: 99%

A microhap panel for kinship analysis through massively parallel sequencing technology

Lin

Gao

et al. 2019

Electrophoresis

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“…(A) Correlation between A e and I n ; (B) correlation between A e and F ST ; (C) correlation between F ST and I n . Ten microhaps described by Voskoboinik et al ( 2018 ) exhibit uncharacteristically high levels of polymorphism (see Figure 3 ) and were excluded from the analysis. Eleven microhaps defined on the X chromosome were also excluded.…”

Section: Resultsmentioning

confidence: 99%

“…Ten highly polymorphic microhaps reported by Voskoboinik et al (2018) stand out from microhaps published in other sources in several ways. Originally defined by locus boundaries rather than by explicit lists of SNP identifiers, these 10 microhaps include more SNPs (14-49 per marker) than any other marker in MicroHapDB.…”

Section: Microhapdb Provides Three Measures Of Allelic Variation Withmentioning

confidence: 99%

“…Microhaps are abundant in the human genome, and thus discovering and ranking them for different purposes is an area of active research interest in the forensics community. In just the last few years, numerous studies presenting new microhap marker collections have been published, together totaling more than 400 markers (Hiroaki et al, 2015 ; Kidd et al, 2018 ; van der Gaag et al, 2018 ; Voskoboinik et al, 2018 ; Chen et al, 2019a ; Staadig and Tillmar, 2019 ; de la Puente et al, 2020 ). While two of these studies also include allele frequency data for multiple population samples—including 83 populations 2 in Kidd et al ( 2018 ) and three populations in van der Gaag et al ( 2018 )—the others present either no frequency data or data for a single population sample, with little overlap between studies.…”

Section: Introductionmentioning

confidence: 99%

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MicroHapDB: A Portable and Extensible Database of All Published Microhaplotype Marker and Frequency Data

Standage¹,

Mitchell²

2020

Front. Genet.

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Microhaplotypes are the subject of significant interest in the forensics community as a promising multipurpose forensic DNA marker for human identification. Microhaplotype markers are composed of multiple SNPs in close proximity, such that a single NGS read can simultaneously genotype the individual SNPs and phase them in aggregate to determine the associated donor haplotype. Abundant throughout the human genome, numerous recent studies have sought to discover and rank microhaplotype markers according to allelic diversity within and among populations. Microhaplotypes provide an appealing alternative to STR markers for human identification and mixture deconvolution, but can also be optimized for ancestry inference or combined with phenotype SNPs for prediction of externally visible characteristics in a multiplex NGS assay. Designing and evaluating panels of microhaplotypes is complicated by the lack of a convenient database of all published data, as well as the lack of population allele frequency data spanning disparate marker collections. We present MicroHapDB, a comprehensive database of published microhaplotype marker and frequency data, as a tool to advance the development of microhaplotype-based human forensics capabilities. We also present population allele frequencies derived from 26 global population samples for all microhaplotype markers published to date, facilitating the design and interpretation of custom multi-source panels. We submit MicroHapDB as a resource for community members engaged in marker discovery, population studies, assay development, and panel and kit design.

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“…Microhaps are abundant in the human genome, and thus discovering and ranking them for different purposes is an area of active research interest in the forensics community. In just the last few years, numerous studies presenting new microhap marker collections have been published, together totaling more than 400 markers (Hiroaki et al, 2015; Kidd et al, 2018; van der Gaag et al, 2018; Voskoboinik et al, 2018; Staadig and Tillmar, 2019; Chen et al, 2019a; de la Puente et al, 2020). While two of these studies also include allele frequency data for multiple population samples—including 83 populations 2 in Kidd et al (2018) and 3 populations in van der Gaag et al (2018)—the others present either no frequency data or data for a single population sample, with little overlap between studies.…”

Section: Introductionmentioning

confidence: 99%

MicroHapDB: a portable and extensible database of all published microhaplotype marker and frequency data

Standage

Mitchell²

2020

Preprint

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2Microhaplotypes are the subject of significant interest in the forensics community as a promising 3 multi-purpose forensic DNA marker for human identification. Microhaplotype markers are 4 composed of multiple SNPs in close proximity, such that a single NGS read can simultaneously 5 genotype the individual SNPs and phase them in aggregate to determine the associated donor 6 haplotype. Abundant throughout the human genome, numerous recent studies have sought 7 to discover and rank microhaplotype markers according to allelic diversity within and among 8 populations. Microhaplotypes provide an appealing alternative to STR markers for human 9 identification and mixture deconvolution, but can also be optimized for ancestry inference or 10 combined with phenotype SNPs for prediction of externally visible characteristics in a multiplex 11 NGS assay. Designing and evaluating panels of microhaplotypes is complicated by the lack of a 12 convenient database of all published data, as well as the lack of population allele frequency data 13 spanning disparate marker collections. We present MicroHapDB, a comprehensive database of 14 published microhaplotype marker and frequency data, as a tool to advance the development of 15 microhaplotype-based human forensics capabilities. We also present population allele frequencies 16 derived from 26 global population samples for all microhaplotype markers published to date, 17 facilitating the design and interpretation of custom multi-source panels. We submit MicroHapDB 18 as a resource for community members engaged in marker discovery, population studies, assay 19 development, and panel and kit design. 20 Well-studied short tandem repeat (STR) markers have formed the basis of forensic human identification 22 methods since the 1990s. The most common strategy in practice today utilizes several fluorescent dyes 23 to type 20 or more STR markers in a single polymerase chain reaction (PCR) followed by capillary 24 electrophoresis (CE) detection (Butler, 2010). The resulting DNA profiles, combined with STR allele 25 frequency estimates, can then be used to calculate match statistics or evaluate the relative weight of evidence 26 1 Standage & Mitchell MicroHapDB v0.5for competing propositions in a likelihood ratio framework (Butler, 2015; Cowell et al., 2015; Bleka et al., 27 2016a,b). Statistics obtained via STR typing can provide high confidence given the number of independent 28 markers in an assay and the multiallelic nature of each marker. 29 Despite impressive recent improvements in DNA sequencing technologies, next-generation sequencing 30 (NGS) assays of single nucleotide polymorphism (SNP) markers have seen slow adoption for forensic 31 human identification. The ability to genotype sufficient numbers of SNPs to achieve suitable statistical 32 power remains beyond the scope of many forensics laboratories. A relevant factor is the forensics 33 community's strong disinclination, on ethical and privacy grounds, to use DNA markers associated 34 with human disease...

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Facilitating complex DNA mixture interpretation by sequencing highly polymorphic haplotypes

Cited by 33 publications

References 17 publications

A microhap panel for kinship analysis through massively parallel sequencing technology

A microhap panel for kinship analysis through massively parallel sequencing technology

MicroHapDB: A Portable and Extensible Database of All Published Microhaplotype Marker and Frequency Data

MicroHapDB: a portable and extensible database of all published microhaplotype marker and frequency data

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