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. 2019 Feb 14;20(1):18.
doi: 10.1186/s12863-019-0723-2.

Characterization of the Extra Copy of TPOX Locus With Tri-Allelic Pattern

Free PMC article

Characterization of the Extra Copy of TPOX Locus With Tri-Allelic Pattern

Qinrui Yang et al. BMC Genet. .
Free PMC article


Background: An STR locus with tri-allelic pattern is occasionally observed in routine forensic casework. The extra copy of TPOX locus with tri-allelic pattern in populations has been assumed to be inserted into an X chromosome, which took place forth before the Bantu expansion in Africa. Nonetheless, the exact location of the duplication and the form of rearrangement in the human genome has not been clarified yet.

Results: In this study, we investigated the extra copy of type 2 tri-allelic pattern at TPOX in various populations. While allele 10 is the major third allele in Africa, allele 11 appears more frequent in America and overwhelming in Chinese and Korean populations, which might attribute to the population substructures. Results from the investigation of family cases showed that the transmission of the extra allele had a similar genetic pattern of autosomal genes. Furthermore, a whole-genome sequencing followed by bioinformatics analysis revealed that the intact form of chromosomal duplication and rearrangement occurred ~ 407 kb away from the authentic TPOX locus on chromosome 2 in two cases. The breakpoints of the insertion were further validated in most other tri-allelic subjects, which can imply the identical origin from the ancestral extra copy. Nevertheless, de novo chromosomal duplication and rearrangement at thyroid peroxidase gene occur in populations.

Conclusions: Instead of the extra allele 10 in African populations, the main third allele at TPOX with tri-allelic pattern is allele 11 in Chinese and Korean populations. The insertion of the extra copy into chromosome 2 occurs in most subjects with tri-allelic pattern at TPOX and demonstrates the transmission of the third allele from parents to offspring. The breakpoints of the ancestral extra copy are defined, which shows evidence of its inheritance from African populations. In addition, the simple validation method would help improve tri-allelic pattern calling, distinguish de novo chromosomal rearrangements, and also count the frequencies among different geographic regions. Therefore, the statistical interpretation of tri-allelic pattern at TPOX could be enhanced during forensic practice.

Keywords: Chromosome 2; Recombination; Short tandem repeats; TPOX; Tri-allelic pattern.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the ethics committee of Shanghai Medical College, Fudan University, and all individuals volunteered for this study based upon written informed consent.

Consent for publication

No details, images or videos relating to any of the study participants are included in this manuscript.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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


Fig. 1
Fig. 1
The number of extra alleles 10 and 11 at TPOX locus in unrelated individuals among populations. As for Europe, Belgium, France and Portugal are included
Fig. 2
Fig. 2
The determination of the genomic location of extra copy of TPOX. a The read depth of sample1 (genome 3) compared to that of a normal genome (control) using IGV. Left panel: the region (position chr2: 1,201,500-1,257,500 bp) with a duplication of SNTG2; Right panel: the region (position chr2: 1,377,500-1,509,999 bp) with a duplication of TPO gene. A pseudo deletion happens in SNTG2 in both genomes, which could be attributable to high G-C content therein. b A total of 18 split reads (of half of the read depth) was observed to be concurrently aligned to the fused region. The vertical solid line signposts the right breakpoint junction where the partial duplication of TPO joins in an inverted orientation to the region of SNTG2 as indicated by the arrows. c The breakpoints (red dashed lines) and flanking sequences. PCR products in Additional file 4: Fig. S2 were used for Sanger sequencing, respectively. The upper panel indicates the right breakpoint junction and its flanking regions. The lower panel indicates the left breakpoint junction where a 52 bp sequence was inserted in-between
Fig. 3
Fig. 3
The detection of two breakpoints in unrelated individuals with tri-allelic pattern at TPOX. a A schematic diagram of the duplication and rearrangement of the extra copy of TPOX. The gray region represents a duplication of SNTG2 and the pink region represents a duplication of TPO. The arrows indicate the direction of genes on chromosome 2. b-e The detection of two breakpoint junctions by CE in a normal individual (b) and three unrelated individuals with tri-allelic pattern at TPOX (c, d, and e)

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