Skip to main content

Advertisement

SpringerLink
Log in

DIP-microhaplotypes: new markers for detection of unbalanced DNA mixtures

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

The identification of a suspect in a degraded and unbalanced DNA mixture has been a challenge for the standard short tandem repeat polymorphisms (STR) typing. Several methods have been introduced to solve this problem, such as DIP-STR, DIP-SNP, and SNP-STR markers. In this study, we proposed DIP-microhaplotype (deletion/insertion linked a chain of SNPs) as a kind of new genetic marker to type the unbalanced and degraded DNA mixture. We established the detection method with ten DIP-microhaplotype markers including 26 SNPs using allele-specific multiplex PCR followed by SNaPshot assay. This novel compound marker allows us to detect the minor DNA with a sensitivity of 1:100 to 1:1000 in a DNA mixture of any gender. Most of the DIP-microhaplotype markers had a relatively high probability of informative alleles with an average informative value (I value) of 0.308. In all, we proposed DIP-microhaplotype as a novel type of DNA marker for the detection of minor contributor from unbalanced DNA mixtures. Due to their inherent shorter length, higher polymorphism, and sensitivity, DIP-microhaplotypes are promising markers for the examination of the degraded and unbalanced mixtures in forensic stains or clinical chimeras.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Qi Y, Wang N, Pang LJ, Zou H, Hu JM, Zhao J, Zhang J, Liu CX, Zhang WJ, Yuan XL, Li F (2015) Identification of potential mutations and genomic alterations in the epithelial and spindle cell components of biphasic synovial sarcomas using a human exome SNP chip. BMC Med Genet 8:69. https://doi.org/10.1186/s12920-015-0144-7

    Article  CAS  Google Scholar 

  2. Druliner BR, Ruan X, Sicotte H, O'Brien D, Liu H, Kocher JA, Boardman L (2018) Early genetic aberrations in patients with sporadic colorectal cancer. Mol Carcinog 57:114–124. https://doi.org/10.1002/mc.22738

    Article  CAS  PubMed  Google Scholar 

  3. Zhang S, Han S, Zhang M, Wang Y (2018) Non-invasive prenatal paternity testing using cell-free fetal DNA from maternal plasma: DNA isolation and genetic marker studies. Leg Med (Tokyo) 32:98–103. https://doi.org/10.1016/j.legalmed.2018.03.009

    Article  CAS  Google Scholar 

  4. Fattorini P, Marrubini G, Bonin S, Bertoglio B, Grignani P, Recchia E, Pitacco P, Procopio F, Cantoni C, Pajnič IZ, Sorçaburu-Cigliero S, Previderè C (2018) Producing standard damaged DNA samples by heating: pitfalls and suggestions. Anal Biochem 549:107–112. https://doi.org/10.1016/j.ab.2018.03.011

    Article  CAS  PubMed  Google Scholar 

  5. Maciejewska A, Jakubowska J, Pawlowski R (2013) Whole genome amplification of degraded and nondegraded DNA for forensic purposes. Int J Legal Med 127:309–319. https://doi.org/10.1007/s00414-012-0764-9

    Article  PubMed  Google Scholar 

  6. Tan JYY, Tan YP, Ng S, Tay AS, Phua YH, Tan WJ, Ong TYR, Chua LM, Syn CKC (2017) A preliminary evaluation study of new generation multiplex STR kits comprising of the CODIS core loci and the European standard set loci. J Forensic Legal Med 52:16–23. https://doi.org/10.1016/j.jflm.2017.07.017

    Article  Google Scholar 

  7. Roewer L (2009) Y chromosome STR typing in crime casework. Forensic Sci Med Pathol 5:77–84. https://doi.org/10.1007/s12024-009-9089-5

    Article  CAS  PubMed  Google Scholar 

  8. Gill P, Brenner CH, Buckleton JS, Carracedo A, Krawczak M, Mayr WR, Morling N, Prinz M, Schneider PM, Weir BS, DNA commission of the International Society of Forensic Genetics (2006) DNA commission of the International Society of Forensic Genetics: recommendations on the interpretation of mixtures. Forensic Sci Int 160:90–101. https://doi.org/10.1016/j.forsciint.2006.04.009

    Article  CAS  PubMed  Google Scholar 

  9. Wang DY, Chang CW, Lagace RE, Calandro LM, Hennessy LK (2012) Developmental validation of the AmpFlSTR(R) Identifiler(R) plus PCR amplification kit: an established multiplex assay with improved performance. J Forensic Sci 57:453–465. https://doi.org/10.1111/j.1556-4029.2011.01963.x

    Article  CAS  PubMed  Google Scholar 

  10. Du W, Feng P, Huang H et al (2019) Technical note: developmental validation of a novel 6-dye typing system with 36 Y-STR loci. Int J Legal Med 133:1015–1027. https://doi.org/10.1007/s00414-018-1864-y

    Article  PubMed  Google Scholar 

  11. Liu H, Li X, Mulero J, Carbonaro A, Short M, Ge J (2016) A convenient guideline to determine if two Y-STR profiles are from the same lineage. Electrophoresis 37:1659–1668. https://doi.org/10.1002/elps.201500566

    Article  CAS  PubMed  Google Scholar 

  12. Du W, Peng Z, Feng C et al (2017) Forensic efficiency and genetic variation of 30 InDels in Vietnamese and Nigerian populations. Oncotarget 8:88934–88940. https://doi.org/10.18632/oncotarget.21494

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cereda G, Biedermann A, Hall D, Taroni F (2014) An investigation of the potential of DIP-STR markers for DNA mixture analyses. Forensic Sci Int Genet 11:229–240. https://doi.org/10.1016/j.fsigen.2014.04.001

    Article  CAS  PubMed  Google Scholar 

  14. Cereda G, Gill RD, Taroni F (2018) A solution for the rare type match problem when using the DIP-STR marker system. Forensic Sci Int Genet 34:88–96. https://doi.org/10.1016/j.fsigen.2017.07.010

    Article  CAS  PubMed  Google Scholar 

  15. Castella V, Gervaix J, Hall D (2013) DIP-STR: highly sensitive markers for the analysis of unbalanced genomic mixtures. Hum Mutat 34:644–654. https://doi.org/10.1002/humu.22280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu J, Li W, Wang J et al (2019) A new set of DIP-SNP markers for detection of unbalanced and degraded DNA mixtures. Electrophoresis 40:1795–1804. https://doi.org/10.1002/elps.201900017

    Article  CAS  PubMed  Google Scholar 

  17. Liu Z, Liu J, Wang J et al (2018) A set of 14 DIP-SNP markers to detect unbalanced DNA mixtures. Biochem Biophys Res Commun 497:591–596. https://doi.org/10.1016/j.bbrc.2018.02.109

    Article  CAS  PubMed  Google Scholar 

  18. Kidd KK, Speed WC, Pakstis AJ, Podini DS, Lagacé R, Chang J, Wootton S, Haigh E, Soundararajan U (2017) Evaluating 130 microhaplotypes across a global set of 83 populations. Forensic Sci Int Genet 29:29–37. https://doi.org/10.1016/j.fsigen.2017.03.014

    Article  CAS  PubMed  Google Scholar 

  19. Oldoni F, Kidd KK, Podini D (2019) Microhaplotypes in forensic genetics. Forensic Sci Int Genet 38:54–69. https://doi.org/10.1016/j.fsigen.2018.09.009

    Article  CAS  PubMed  Google Scholar 

  20. Kidd KK, Pakstis AJ, Speed WC, Lagace R, Wootton S, Chang J (2018) Selecting microhaplotypes optimized for different purposes. Electrophoresis 39:2815–2823. https://doi.org/10.1002/elps.201800092

    Article  CAS  PubMed  Google Scholar 

  21. Kidd KK (2016) Proposed nomenclature for microhaplotypes. Hum Genomics 10:16. https://doi.org/10.1186/s40246-016-0078-y

    Article  PubMed  PubMed Central  Google Scholar 

  22. Stanciu F, Vladu S, Cutar V et al (2013) Genetic parameters and allele frequencies of five new European standard set STR loci (D10S1248, D22S1045, D2S441, D1S1656, D12S391) in the population of Romania. Croat Med J 54:232–237. https://doi.org/10.3325/cmj.2013.54.232

    Article  PubMed  PubMed Central  Google Scholar 

  23. Turchi C, Melchionda F, Pesaresi M, Tagliabracci A (2019) Evaluation of a microhaplotypes panel for forensic genetics using massive parallel sequencing technology. Forensic Sci Int Genet 41:120–127. https://doi.org/10.1016/j.fsigen.2019.04.009

    Article  CAS  PubMed  Google Scholar 

  24. Tan Y, Wang L, Wang H, Tian H, Li Z, Wang Q, Jian H, Cao S, Liang W, Zhang L (2017) An investigation of a set of DIP-STR markers to detect unbalanced DNA mixtures among the southwest Chinese Han population. Forensic Sci Int Genet 31:34–39. https://doi.org/10.1016/j.fsigen.2017.08.014

    Article  CAS  PubMed  Google Scholar 

  25. Parkin B, Londono-Joshi A, Kang Q, Tewari M, Rhim AD, Malek SN (2017) Ultrasensitive mutation detection identifies rare residual cells causing acute myelogenous leukemia relapse. J Clin Invest 127:3484–3495. https://doi.org/10.1172/JCI91964

    Article  PubMed  PubMed Central  Google Scholar 

  26. Debeljak M, Mocci E, Morrison MC, Pallavajjalla A, Beierl K, Amiel M, Noë M, Wood LD, Lin MT, Gocke CD, Klein AP, Fuchs EJ, Jones RJ, Eshleman JR (2017) Haplotype counting for sensitive chimerism testing: potential for early leukemia relapse detection. J Mol Diagn 19:427–436. https://doi.org/10.1016/j.jmoldx.2017.01.005

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bennett CW, Berchem G, Kim YJ, El-Khoury V (2016) Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer. Oncotarget 7:71013–71035. https://doi.org/10.18632/oncotarget.11717

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pasha HA, Rezk NA, Riad MA (2019) Circulating cell free nuclear DNA, mitochondrial DNA and global DNA methylation: potential noninvasive biomarkers for breast cancer diagnosis. Cancer Investig 37:432–439. https://doi.org/10.1080/07357907.2019.1663864

    Article  CAS  Google Scholar 

  29. Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C, Lamy T, le Prisé PY, Beauplet A, Bories D, Semana G, Quelvennec E (2002) Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood 99:4618–4625. https://doi.org/10.1182/blood.v99.12.4618

    Article  CAS  PubMed  Google Scholar 

  30. Zhu J, Lv M, Zhou N, Chen D, Jiang Y, Wang L, He W, Peng D, Li Z, Qu S, Wang Y, Wang H, Luo H, An G, Liang W, Zhang L (2019) Genotyping polymorphic microhaplotype markers through the Illumina((R)) MiSeq platform for forensics. Forensic Sci Int Genet 39:1–7. https://doi.org/10.1016/j.fsigen.2018.11.005

    Article  CAS  PubMed  Google Scholar 

  31. Khubrani YM, Hallast P, Jobling MA, Wetton JH (2019) Massively parallel sequencing of autosomal STRs and identity-informative SNPs highlights consanguinity in Saudi Arabia. Forensic Sci Int Genet 43:102164. https://doi.org/10.1016/j.fsigen.2019.102164

    Article  CAS  PubMed  Google Scholar 

  32. Barrio PA, Martin P, Alonso A et al (2019) Massively parallel sequence data of 31 autosomal STR loci from 496 Spanish individuals revealed concordance with CE-STR technology and enhanced discrimination power. Forensic Sci Int Genet 42:49–55. https://doi.org/10.1016/j.fsigen.2019.06.009

    Article  CAS  PubMed  Google Scholar 

  33. Bennett L, Oldoni F, Long K, Cisana S, Madella K, Wootton S, Chang J, Hasegawa R, Lagacé R, Kidd KK, Podini D (2019) Mixture deconvolution by massively parallel sequencing of microhaplotypes. Int J Legal Med 133:719–729. https://doi.org/10.1007/s00414-019-02010-7

    Article  PubMed  Google Scholar 

  34. Chen P, Deng C, Li Z, Pu Y, Yang J, Yu Y, Li K, Li D, Liang W, Zhang L, Chen F (2019) A microhaplotypes panel for massively parallel sequencing analysis of DNA mixtures. Forensic Sci Int Genet 40:140–149. https://doi.org/10.1016/j.fsigen.2019.02.018

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was funded by the National Natural Science Foundation of China [30900593 and 81701868], the Natural Science Foundation of Shanxi Province, China [201601D011091], and Shanxi Provincial Key Research and Development Project (CN) [201803D31069].

Author information

Authors and Affiliations

  1. Department of Forensic Biology, School of Forensic Medicine, Shanxi Medical University, Wenhua Street 55#, Jinzhong, 030619, Shanxi, People’s Republic of China

    Jinding Liu, Ting Hao, Xiaojuan Cheng, Jiaqi Wang, Wenyan Li, Zidong Liu, Jie Shi, Zeqin Li, Jianbo Ren, Keming Yun & Gengqian Zhang

Authors
  1. Jinding Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ting Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaojuan Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiaqi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenyan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zidong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jie Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zeqin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jianbo Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Keming Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gengqian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Keming Yun or Gengqian Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committee of Shanxi Medical University +2019LL096) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 1241 kb)

ESM 2

(DOC 189 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Hao, T., Cheng, X. et al. DIP-microhaplotypes: new markers for detection of unbalanced DNA mixtures. Int J Legal Med 135, 13–21 (2021). https://doi.org/10.1007/s00414-020-02288-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-020-02288-y

Keywords

Search

Navigation