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Practical forensic use of kinship determination using high-density SNP profiling based on a microarray platform, focusing on low-quantity DNA

  • Kayoko Yagasaki
    Correspondence
    Corresponding author at: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan.
    Affiliations
    Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7–3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan

    Forensic Science Laboratory, Tokyo Metropolitan Police Department, 3-35-21, Shakujiidai, Nerima Ward, Tokyo 177-0045, Japan
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  • Akihiko Mabuchi
    Affiliations
    Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7–3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan
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  • Toshihide Higashino
    Affiliations
    Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7–3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan
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  • Jing Hao Wong
    Affiliations
    Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7–3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan
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  • Nao Nishida
    Affiliations
    Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7–3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan

    Genome Medical Science Project, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba 272-8516, Japan
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  • Akihiro Fujimoto
    Affiliations
    Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7–3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan
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  • Katsushi Tokunaga
    Affiliations
    Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7–3-1, Hongo, Bunkyo Ward, Tokyo 113-0033, Japan

    Genome Medical Science Project, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku word, Tokyo 162-8655, Japan
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      Highlights

      • Tolerance of microarray SNP genotyping for low-quantity DNA was investigated.
      • Feasibility of kinship discrimination analysis in forensic genetics was evaluated.
      • SNP profile with low data quality contains many false heterozygote SNPs.
      • We made it clear how false heterozygote SNPs affect kinship discrimination analysis.
      • We developed a new method to obtain accurate kinship discrimination analysis results.

      Abstract

      Instead of traditional short tandem repeat (STR) profiling, the genetic genealogy method, which uses hundreds of thousands of single nucleotide polymorphisms (SNPs) spread across genome-wide, has emerged as a powerful kinship determination tool and recently attracted great attention in forensic genetics.
      In this study, we explored the tolerance and viability of kinship discrimination based on a high-density SNP profile for forensic DNA, especially focusing on low-quantity DNA. Using the Affymetrix Genome-Wide Human SNP Array 6.0 platform (Thermo Fisher Scientific), the influence of low-quantity DNA on SNP genotype determination was evaluated. The low-quantity DNA samples failed once every few samples, the generated SNP profile had low data quality. Our investigation revealed that the SNP profile with low data quality contained many genotyping errors in which the SNP genotype changed from homozygote to heterozygote. The kinship discrimination analysis using KING software was directly influenced by these genotyping errors, which was confirmed that some unrelated pairs were mis-specified as 4th-degree relatives. We confirmed that the false heterozygous SNPs resulted in an inflation of kinship coefficient and a decrease of non-shared allele between a tested pair.
      To eliminate the influence of these genotyping errors and acquire an accurate kinship discrimination result, we developed a novel method to select only the robust SNPs, which stably give the genotype determination with high accuracy even in SNP profiles with low data quality. The application of our novel method led to the improved results of kinship discrimination up to the same level as in the SNP profile with high data quality.
      In addition, this study demonstrated the advantage of kinship analysis using a high-density SNP profile in the forensic field. It is well known that likelihood ratio calculation based on autosomal STR profile, which is the most commonly applied approach, has difficulty in gaining true kinship analysis results, especially when the relationship between the tested two individuals is more biologically distant. We showed the kinship discrimination analysis with a high-density SNP profile is more suitable for the case without close relatives, using the real case data. Although further study with larger samples will be necessary, this study indicated that practical forensic use of kinship determination with a high-density SNP profile would bring benefits to the forensic field.

      Keywords

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