TY - JOUR
T1 - Increasing the discrimination power of ancestry- and identity-informative SNP loci within the ForenSeq™ DNA Signature Prep Kit
AU - King, Jonathan L.
AU - Churchill, Jennifer D.
AU - Novroski, Nicole M.M.
AU - Zeng, Xiangpei
AU - Warshauer, David H.
AU - Seah, Lay Hong
AU - Budowle, Bruce
N1 - Funding Information:
This work was supported in part by awards 2012-DNBXK033 and 2015-DN-BX-K067, awarded by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice . The opinions, findings, and conclusions or recommendations expressed are those of the authors and do not necessarily reflect those of the U.S. Department of Justice. The authors would like to thank August Woerner, Rodrigo Moura-Neto, and Rosane Silva, for their invaluable discussions and guidance. Additionally, the authors would like to thank Illumina and Verogen, particularly Benedict (Al) Bodota, John Walsh, Kathryn Stephens, Joe Varlaro, and Cydne Holt, for their support in this study. Lastly, the authors wish to thank the anonymous reviewers whose comments improved the manuscript immensely.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/9
Y1 - 2018/9
N2 - The use of single nucleotide polymorphisms (SNPs) in forensic genetics has been limited to challenged samples with low template and/or degraded DNA. The recent introduction of massively parallel sequencing (MPS) technologies has expanded the potential applications of these markers and increased the discrimination power of well-established loci by considering variation in the flanking regions of target loci. The ForenSeq Signature Preparation Kit contains 165 SNP amplicons for ancestry- (aiSNPs), identity- (iiSNPs), and phenotype-inference (piSNPs). In this study, 714 individuals from four major populations (African American, AFA; East Asian, ASN; US Caucasian, CAU; and Southwest US Hispanic, HIS) previously reported by Churchill et al. [Forensic Sci Int Genet. 30 (2017) 81–92; DOI: https://doi.org/10.1016/j.fsigen.2017.06.004] were assessed using STRait Razor v2s to determine the level of diversity in the flanking regions of these amplicons. The results show that nearly 70% of loci showed some level of flanking region variation with 22 iiSNPs and 8 aiSNPs categorized as microhaplotypes in this study. The heterozygosities of these microhaplotypes approached, and in one instance surpassed, those of some core STR loci. Also, the impact of the flanking region on other forensic parameters (e.g., power of exclusion and power of discrimination) was examined. Sixteen of the 94 iiSNPs had an effective allele number greater than 2.00 across the four populations. To assess what effect the flanking region information had on the ancestry inference, genotype probabilities and likelihood ratios were determined. Additionally, concordance with the ForenSeq UAS and Nextera Rapid Capture was evaluated, and patterns of heterozygote imbalance were identified. Pairwise comparison of the iiSNP diplotypes determined the probability of detecting a mixture (i.e., observing ≥ 3 haplotypes) using these loci alone was 0.9952. The improvement in random match probabilities for the full regions over the target iiSNPs was found to be significant. When combining the iiSNPs with the autosomal STRs, the combined match probabilities ranged from 6.40 × 10−73 (ASN) to 1.02 × 10-79 (AFA).
AB - The use of single nucleotide polymorphisms (SNPs) in forensic genetics has been limited to challenged samples with low template and/or degraded DNA. The recent introduction of massively parallel sequencing (MPS) technologies has expanded the potential applications of these markers and increased the discrimination power of well-established loci by considering variation in the flanking regions of target loci. The ForenSeq Signature Preparation Kit contains 165 SNP amplicons for ancestry- (aiSNPs), identity- (iiSNPs), and phenotype-inference (piSNPs). In this study, 714 individuals from four major populations (African American, AFA; East Asian, ASN; US Caucasian, CAU; and Southwest US Hispanic, HIS) previously reported by Churchill et al. [Forensic Sci Int Genet. 30 (2017) 81–92; DOI: https://doi.org/10.1016/j.fsigen.2017.06.004] were assessed using STRait Razor v2s to determine the level of diversity in the flanking regions of these amplicons. The results show that nearly 70% of loci showed some level of flanking region variation with 22 iiSNPs and 8 aiSNPs categorized as microhaplotypes in this study. The heterozygosities of these microhaplotypes approached, and in one instance surpassed, those of some core STR loci. Also, the impact of the flanking region on other forensic parameters (e.g., power of exclusion and power of discrimination) was examined. Sixteen of the 94 iiSNPs had an effective allele number greater than 2.00 across the four populations. To assess what effect the flanking region information had on the ancestry inference, genotype probabilities and likelihood ratios were determined. Additionally, concordance with the ForenSeq UAS and Nextera Rapid Capture was evaluated, and patterns of heterozygote imbalance were identified. Pairwise comparison of the iiSNP diplotypes determined the probability of detecting a mixture (i.e., observing ≥ 3 haplotypes) using these loci alone was 0.9952. The improvement in random match probabilities for the full regions over the target iiSNPs was found to be significant. When combining the iiSNPs with the autosomal STRs, the combined match probabilities ranged from 6.40 × 10−73 (ASN) to 1.02 × 10-79 (AFA).
KW - Bioinformatics
KW - FGx
KW - ForenSeq
KW - Massively parallel sequencing
KW - Microhaplotypes
KW - SNPs
UR - http://www.scopus.com/inward/record.url?scp=85048802168&partnerID=8YFLogxK
U2 - 10.1016/j.fsigen.2018.06.005
DO - 10.1016/j.fsigen.2018.06.005
M3 - Article
C2 - 29935396
AN - SCOPUS:85048802168
SN - 1872-4973
VL - 36
SP - 60
EP - 76
JO - Forensic Science International: Genetics
JF - Forensic Science International: Genetics
ER -