Genetic analysis of tri-allelic patterns at the CODIS STR loci


In the routine of autosomal STR genotyping for forensic aims, tri-allelic patterns could be occasionally observed at a single locus in phenotypically normal individuals. Two predominant types of tri-allelic variants have been nominated. Uneven intensities of three alleles are normally considered as the Type 1 pattern, and balanced height of three alleles are considered as the Type 2 pattern. In this study, the prevalence of tri-allelic patterns at the CODIS STR loci was investigated in global populations based on previous reports. The frequencies of the Type 1 and Type 2 pattern manifest a correlation with the germline mutation rates at the CODIS STR loci. The irregular high frequencies of the Type 2 pattern at TPOX with low germline mutation rates could attribute to the stable inheritance of genomic rearrangement from ancestral origin. Furthermore, results from genetic pattern analysis show that only a single allele from STRs with the Type 1 pattern could be transmitted from parents to offsprings, while a single allele and a combination of two alleles from STRs with the Type 2 pattern present an equal opportunity of transmission from parents to offsprings. Altogether, these results provide a genetic portrait of STRs with tri-allelic patterns, which will help the genetic interpretation of tri-allelic patterns in forensic practice.

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

Fig. 1
Fig. 2
Fig. 3


  1. Amos W, Flint J, Xu X (2008) Heterozygosity increases microsatellite mutation rate, linking it to demographic history. BMC Genet.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Brinkmann B, Klintschar M, Neuhuber F, Hühne J, Rolf B (1998) Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am J Hum Genet 62:1408–1415

    CAS  Article  Google Scholar 

  3. Clayton TM, Guest JL, Urquhart AJ, Gill PD (2004) A genetic basis for anomalous band patterns encountered during DNA STR profiling. J Forensic Sci 49:1207–1214

    CAS  Article  Google Scholar 

  4. Crouse CA, Rogers S, Amiott E, Gibson S, Masibay A (1999) Analysis and interpretation of short tandem repeat microvariants and three-banded allele patterns using multiple allele detection systems. J Forensic Sci 44:87–94

    CAS  Article  Google Scholar 

  5. Díaz V, Rivas P, Carracedo A (2009) The presence of tri-allelic TPOX genotypes in Dominican Population. Forensic Sci Int Genet Suppl Ser 2:371–372

    Article  Google Scholar 

  6. Eboreime J, Choi SK, Yoon SR, Arnheim N, Calabrese P (2016) Estimating exceptionally rare germline and somatic mutation frequencies via next generation sequencing. PLoS ONE 11:e0158340

    Article  Google Scholar 

  7. Girirajan S, Campbell CD, Eichler EE (2011) Human copy number variation and complex genetic disease. Annu Rev Genet 45:203–226

    CAS  Article  Google Scholar 

  8. Gu W, Zhang F, Lupski JR (2008) Mechanisms for human genomic rearrangements. Pathogenetics 1:4

    Article  Google Scholar 

  9. Hastings PJ, Ira G, Lupski JR (2009) A microhomology-mediated break-induced replication model for the origin of human copy number variation. PLoS Genet 5:e1000327

    CAS  Article  Google Scholar 

  10. Jiang E, Pan J, Han M, Chen L, Ma Q, Wei J, Huang Y, Feng S, Sun Q, Xiao P, Zheng Z (2016) Tri-allelic patterns at the D7S820 locus detected in two generations of a Chinese family. Int J Legal Med 130:23–26

    Article  Google Scholar 

  11. Lane AB (2008) The nature of tri-allelic TPOX genotypes in African populations. Forensic Sci Int Genet 2:134–137

    CAS  Article  Google Scholar 

  12. Picanço JB, Raimann PE, Paskulin GA, Alvarez L, Amorim A, Batista dos Santos SE, Alho CS (2014) Tri-allelic pattern at the TPOX locus: a familial study. Gene 535:353–358

    Article  Google Scholar 

  13. Rolf B, Wiegand P, Brinkmann B (2002) Somatic mutations at STR loci—a reason for three-allele pattern and mosaicism. Forensic Sci Int 126:200–202

    CAS  Article  Google Scholar 

  14. Shao C, Lin M, Zhou Z, Zhou Y, Shen Y, Xue A, Zhou H, Tang Q, Xie J (2016) Mutation analysis of 19 autosomal short tandem repeats in Chinese Han population from Shanghai. Int J Legal Med 130:1439–1444

    Article  Google Scholar 

  15. Stankiewicz P, Lupski JR (2002) Genome architecture, rearrangements and genomic disorders. Trends Genet 18:74–82

    CAS  Article  Google Scholar 

  16. Sun H, Liu S, Zhang Y, Whittle MR (2014) Comparison of southern Chinese Han and Brazilian Caucasian mutation rates at autosomal short tandem repeat loci used in human forensic genetics. Int J Legal Med 128:1–9

    Article  Google Scholar 

  17. Xie J, Shao C, Zhou Y, Zhu W, Xu H, Liu Z, Zhao Z (2014) Genetic distribution on 20 STR loci from the Han population in Shanghai, China. Forensic Sci Int Genet 9:e30–e31

    CAS  Article  Google Scholar 

  18. Yang Q, Liu B, Shao C, Zhou Y, Yao Y, Pan Y, Sun K, Xu H, Li C, Wei T, Zhou Y, Tang Q, Xie J (2019) Characterization of the extra copy of TPOX locus with tri-allelic pattern. BMC Genet 20:18

    Article  Google Scholar 

  19. Yang Q, Li M, Sun K, Wang Q, Shao C, Liu Y, Xu H, Zhang S, Bian Y, Gao Y, Li C, Liu Y, Xie J (2020) Genetic analysis of type 2 tri-allelic pattern at TPOX locus in the Chinese Han population. Mol Genet Genomics 295:933–939.

    CAS  Article  Google Scholar 

  20. Yizhak K, Aguet F, Kim J, Hess JM, Kübler K, Grimsby J, Frazer R, Zhang H, Haradhvala NJ, Rosebrock D, Livitz D, Li X, Arich-Landkof E, Shoresh N, Stewart C, Segrè AV, Branton PA, Polak P, Ardlie KG, Getz G (2019) RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science 364:970

    Article  Google Scholar 

  21. Zogopoulos G, Ha KCH, Naqib F, Moore S, Kim H, Montpetit A, Robidoux F, Laflamme P, Cotterchio M, Greenwood C, Scherer SW, Zanke B, Hudson TJ, Bader GD, Gallinger S (2007) Germ-line DNA copy number variation frequencies in a large North American population. Hum Genet 122:345–353

    CAS  Article  Google Scholar 

Download references


This work was supported by National Natural Science Foundation of China (81571853).

Author information




QY, YS, JX conceived and designed the study. CS and YL contributed to sample collection of Type 1 and Type 2 tri-allelic patterns. HX, YZ and ZL conducted the investigation of case reports in literatures. QY, KS and QT conducted statistical analysis of tri-allelic cases. QY and YS wrote the paper, to which all authors contributed. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jianhui Xie.

Ethics declarations

Conflict of interest

QY declares that she has no conflict of interest. YS declares that she has no conflict of interest. CS declares that he has no conflict of interest. YL declares that he has no conflict of interest. HX declares that she has no conflict of interest. YZ declares that she has no conflict of interest. ZL declares that she has no conflict of interest. KS declares that she has no conflict of interest. QT declares that he has no conflict of interest. JX declares that he has no conflict of interest.

Additional information

Publisher's Note

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

Communicated by Stefan Hohmann.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 700 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, Q., Shen, Y., Shao, C. et al. Genetic analysis of tri-allelic patterns at the CODIS STR loci. Mol Genet Genomics (2020).

Download citation


  • Tri-allelic genotype
  • Genetic variants
  • Paternity testing
  • Forensic genetics