Mixture deconvolution by massively parallel sequencing of microhaplotypes

Bennett, Lindsay; Oldoni, Fabio; Long, Kelly; Cisana, Selena; Madella, Katrina; Wootton, Sharon; Chang, Joseph; Hasegawa, Ryo; Lagacé, Robert; Kídd, Kenneth K.; Podini, Daniele

doi:10.1007/s00414-019-02010-7

Cited by 52 publications

(38 citation statements)

References 42 publications

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“…Several groups recently proposed MPS-based microhaplotype panels for specific applications [4]. For example, microhaplotype panels with a high effective number of alleles (A e ) [5] will yield high random match probabilities (RMP) and high probabilities for mixture deconvolution [6][7][8]; panels focused on ancestry inference utilize MH loci with high informativeness for assignment (I n ) [5,9]; and panels with small cores (e.g., the distance between the most 5' and 3' polymorphic sites) and correspondingly a small amplicon size should generally work better on small amounts of fragmented DNA [10][11][12]. While MH loci can convey more information on identity and ancestry than the same number of individual SNPs [13], standardized MPS solutions for establishing MH panels are currently not commercially available.…”

Section: Introductionmentioning

confidence: 99%

“…While MH loci can convey more information on identity and ancestry than the same number of individual SNPs [13], standardized MPS solutions for establishing MH panels are currently not commercially available. There is great enthusiasm among forensic researchers to now expand the success of SNPs and establish the next-generation of forensic markers based on multiallelic microhaplotypes [7,8,[10][11][12][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Validation of novel forensic DNA markers using multiplex microhaplotype sequencing

Gandotra¹,

Speed²,

Qin

et al. 2020

Forensic Science International: Genetics

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Microhaplotypes (MH) are comprised of multiple single nucleotide polymorphisms (SNPs) that are located within 300 bases of genomic sequence. Improved tools are needed to facilitate broader application of microhaplotypes in a diverse range of populations and forensic settings. We designed an assay for multiplex sequencing of 90 microhaplotypes (mMHseq) that include 46 MH loci with high Effective Number of Alleles (A e) from previous studies [1], and 44 high A e MH loci containing between four to fourteen SNPs that were identified from the 1000 Genomes (1KG) Project. The unique design of mMHseq integrates a novel method for multiplex amplification from small DNA amounts, and multiplex sequencing of 48 samples in a single MiSeq run to detect all relevant MH variation. Assay performance was evaluated in a cohort of 156 individuals from seven different world populations from Africa, Asia, and Europe. Three of those populations from East Africa (Chagga, Sandawe, and Zaramo) and one from Eastern Europe (Adygei) had sufficient individuals sequenced by the assay to be included in statistical analyses with the 26 1KG populations. For those 30 populations the mean global average A e was 5.08 (range: 2.7-11.54) and mean informativeness for biogeographic variation (I n) was 0.30 (range: 0.08-0.70). Eighty-five novel SNPs were detected in 58 of the 90 microhaplotypes. Open-source, web-based software was developed to visualize haplotype phase data for each microhaplotype and individual. Our approach for multiplex microhaplotype sequencing can be customized and expanded as novel loci are being discovered.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Validation of novel forensic DNA markers using multiplex microhaplotype sequencing

Gandotra¹,

Speed²,

Qin

et al. 2020

Forensic Science International: Genetics

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“…Currently, a new type of genetic marker, known as microhaplotypes or microhaps (MHs), has been introduced into the field of forensic for different application purposes . A MH locus is defined by at least two SNPs closely genetically linked within a small region, and the allelic combinations of each SNP at a specific locus are defined as alleles, regarding a haplotype as a single allele .…”

Section: Introductionmentioning

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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“…(1) 87 microhaps (Turchi, Melchionda, Pesaresi, & Tagliabracci, 2019); (2) 38 microhaps (Bennett et al, 2019); and (3) 90 microhaps we are validating at Yale (unpublished data). A Venn diagram shows 24 microhap loci common to these three panels; all 24 have extensive population data from the Kidd et al (2017) study.…”

Section: Jannine Forstmentioning

confidence: 75%

2020 National Institute of Justice Forensic Science Research and Development Symposium

2020

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Mixture deconvolution by massively parallel sequencing of microhaplotypes

Cited by 52 publications

References 42 publications

Validation of novel forensic DNA markers using multiplex microhaplotype sequencing

Validation of novel forensic DNA markers using multiplex microhaplotype sequencing

A microhap panel for kinship analysis through massively parallel sequencing technology

2020 National Institute of Justice Forensic Science Research and Development Symposium

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