Inconsistent genotyping call at DYS389 locus and implications for interpretation
The male-specific Y chromosome short tandem repeat (STR) locus is used widely in forensic case, which are useful molecular tool to providing the biological evidence for male/female mixture and paternal lineage cases. The Y-STR analysis has been greatly facilitated by advent of commercial multiplex kit. However, even with well-designed robust multiplex kit, abnormal genotyping profile may be observed when encountering with mutations, such as deletion/duplication within the target region or mutation at the primer binding site. In this study, a single-allele shift by five nucleotides for the DYS389I marker between the AmpFlSTR® Yfiler® and Yfiler® Plus PCR amplification kits while the same allele count for DYS389II was observed in eight unrelated Chinese male individuals. After further investigations by re-amplified with three additional multiplex kits, sanger, and next-generation sequencing, the discordance was finally proven caused by existing rare mutation in those sample, which contained two adjacent SNPs only one base apart in the sequence. This paper describes the molecular basis of the discordance at DYS389I genotyping between different commercial multiplex kits and could provide available information for enhancing of interpretation of abnormal Y-STR genotyping in forensic practice.
KeywordsY-STR DYS389 Mutation Genotyping Sequencing
This project was supported by the National Natural Science Foundation of China (No. 81330073).
Compliance with ethical standards
Informed consent was obtained from all participants prior to participation in this study. All experiments of this study were carried out in accordance with the guidelines and regulations of the Ethical Committee of Beijing Institute of Genomics, Chinese Academy of Sciences (approved number: 2017033).
Conflict of interest
The authors declare that they have no competing interests.
- 6.Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, Repping S, Pyntikova T, Ali J, Bieri T, Chinwalla A, Delehaunty A, Delehaunty K, Du H, Fewell G, Fulton L, Fulton R, Graves T, Hou SF, Latrielle P, Leonard S, Mardis E, Maupin R, McPherson J, Miner T, Nash W, Nguyen C, Ozersky P, Pepin K, Rock S, Rohlfing T, Scott K, Schultz B, Strong C, Tin-Wollam A, Yang SP, Waterston RH, Wilson RK, Rozen S, Page DC (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423(6942):825–837. https://doi.org/10.1038/nature01722 CrossRefPubMedGoogle Scholar
- 7.Rozen S, Skaletsky H, Marszalek JD, Minx PJ, Cordum HS, Waterston RH, Wilson RK, Page DC (2003) Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. 423 (6942): 873–876Google Scholar
- 8.Goedbloed M, Vermeulen M, Fang RN, Lembring M, Wollstein A, Ballantyne K, Lao O, Brauer S, Krüger C, Roewer L (2009) Comprehensive mutation analysis of 17 Y-chromosomal short tandem repeat polymorphisms included in the AmpFlSTR® Yfiler® PCR amplification kit. Int J Legal Med 123(6):471–482. https://doi.org/10.1007/s00414-009-0342-y CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Gusmao L, Butler JM, Carracedo A, Gill P, Kayser M, Mayr WR, Morling N, Prinz M, Roewer L, Tyler-Smith C, Schneider PM (2006) DNA Commission of the International Society of Forensic Genetics (ISFG): an update of the recommendations on the use of Y-STRs in forensic analysis. Int J Legal Med 120(4):191–200. https://doi.org/10.1007/s00414-005-0026-1 CrossRefPubMedGoogle Scholar
- 10.Butler JM (2005) Forensic DNA Typing: Biology, Technology, and Genetics of STR Markers, 2nd ed., Elsevier Academic Press, New YorkGoogle Scholar