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Research paper| Volume 25, P198-209, November 2016

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing

  • Frank R. Wendt
    Correspondence
    Corresponding author at: Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, CBH−250, Fort Worth, TX,76107, USA.
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA
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  • David H. Warshauer
    Affiliations
    Promega Corporation, 2800 Woods Hollow Rd, Madison, WI, 53711, USA
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  • Xiangpei Zeng
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA
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  • Jennifer D. Churchill
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA
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  • Nicole M.M. Novroski
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA
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  • Bing Song
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA
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  • Jonathan L. King
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA
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  • Bobby L. LaRue
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA

    Department of Forensic Science, College of Criminal Justice, Sam Houston State University, 1003 Bowers Blvd., Huntsville, TX, 77341, USA
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  • Bruce Budowle
    Affiliations
    Institute of Applied Genetics, Department of Molecular and Medical Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA

    Center of Excellence in Genomic Medicine (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia
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Published:September 20, 2016DOI:https://doi.org/10.1016/j.fsigen.2016.09.005
Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing
Previous ArticleDNA Commission of the International Society for Forensic Genetics: Recommendations on the validation of software programs performing biostatistical calculations for forensic genetics applications
Next ArticleCharacterization of genetic sequence variation of 58 STR loci in four major population groups

      Highlights

      • •
        Length-based allele frequencies and heterozygosities are similar to previous U.S. population data for these 68 INDELs.
      • •
        Sequence variation was observed adjacent to 42 INDELs.
      • •
        Sequence variation generally increased heterozygosity and decreased single-locus random match probabilities.
      • •
        Previously reported non-STR containing INDELs were shown to be part of short tandem repeats.
      • •
        The STR Allele Identification Tool: Razor (STRait Razor) successfully mined massively parallel sequencing data for INDELs.

      Abstract

      Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The Nextera™ Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well-characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome.

      Keywords

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      Article info

      Publication history

      Published online: September 20, 2016
      Accepted: September 19, 2016
      Received in revised form: August 1, 2016
      Received: May 28, 2016

      Identification

      DOI: https://doi.org/10.1016/j.fsigen.2016.09.005

      Copyright

      © 2016 Elsevier Ireland Ltd. All rights reserved.

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