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Annals of Hematology

, Volume 98, Issue 5, pp 1279–1291 | Cite as

Multiplex STR panel for assessment of chimerism following hematopoietic stem cell transplantation (HSCT)

  • Wui Chuen Chia
  • Tze Sean Khoo
  • S Fadilah S. Abdul Wahid
  • Noor Farisah Abdul Razak
  • Hafiza Alauddin
  • Raja Zahratul Azma Raja Sabudin
  • Ainoon Othman
  • Roshida Hassan
  • Noor Hamidah HussinEmail author
Original Article
  • 81 Downloads

Abstract

Short tandem repeat (STR) analysis is used in chimerism monitoring after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with various hematologic malignancies. Commercial forensic STR kits often contain loci with huge differences in power of discrimination (PD) across populations, causing some loci to be less informative for chimerism analysis in certain populations. This study aimed to construct a new STR multiplex panel with highly informative loci for efficient chimerism analysis. Thirteen STR markers which exhibit high PD (> 0.9) in at least 80% of 50 populations globally were selected to form a new panel and used in STR analysis of 253 Malaysian subjects. Cumulative power of discrimination (CPD) and combined power of exclusion (CPE) were determined from 253 Malaysian individuals. Loci informativity was assessed and compared to the commercial AmpFLSTR Identifiler PCR Amplification kit in 14 donor–recipient pairs. The new panel had detected 202 unique alleles including five novel alleles from the 253 individuals with high CPD and CPE (> 0.99999999999999999 and > 0.999999997 respectively). All loci from the new panel in the donor–recipient pair analysis showed higher than 50% informativity, while five loci from the commercial kit demonstrated lower than 50% informativity. Four loci from the new panel ranked the highest informativity. A sequenced allelic ladder which consists of 202 unique alleles from the 253 subjects was also developed to ensure accurate allele designation. The new 13-loci STR panel, thus, could serve as an additional powerful, accurate, and highly informative panel for chimerism analysis for HSCT patients.

Keywords

Short tandem repeats (STR) Microsatellite Hematopoietic stem cell transplantation (HSCT) Chimerism Polymerase chain reaction (PCR) Multiplex PCR 

Abbreviations

BLAST

Basic Local Alignment Search Tool

CPD

Cumulative power of discrimination

CPE

Combined power of exclusion

CV

Coefficient of variance

GD

Gene diversity

He

Expected heterozygosity

Ho

Observed heterozygosity

HSCT

Hematopoietic stem cell transplantation

HWE

Hardy–Weinberg equilibrium

MEC

Mean paternity exclusion chance

PCR

Polymerase chain reaction

PDF

Power of discrimination for female

PDM

Power of discrimination for male

PE

Probability of exclusion

PI

Typical paternity index

PIC

Polymorphism information content

PMF

Matching probability for female

PMM

Matching probability for male

SD

Standard deviation

STR

Short tandem repeat

UKMMC

Universiti Kebangsaan Malaysia Medical Centre

Notes

Acknowledgements

The authors thank Rozi Hanisa from the National Blood Centre, Malaysia, for collecting the samples in this study.

Author contributions

All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Funding

This study was supported by ERGS Grant (ERGS/1/2012/SKK09/UKM/01/3), Ministry of Education, Malaysia.

Compliance with ethical standards

This study was approved by the ethics committee of the UKM Medical Centre, Malaysia.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2019_3626_MOESM1_ESM.pdf (658 kb)
ESM 1 (PDF 657 kb)
277_2019_3626_MOESM2_ESM.docx (13 kb)
ESM 2 (DOCX 12 kb)
277_2019_3626_MOESM3_ESM.pdf (330 kb)
ESM 3 (329  kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Wui Chuen Chia
    • 1
  • Tze Sean Khoo
    • 2
  • S Fadilah S. Abdul Wahid
    • 3
  • Noor Farisah Abdul Razak
    • 1
  • Hafiza Alauddin
    • 1
  • Raja Zahratul Azma Raja Sabudin
    • 1
  • Ainoon Othman
    • 4
  • Roshida Hassan
    • 5
  • Noor Hamidah Hussin
    • 1
    Email author
  1. 1.Hematology Unit, Department of Pathology, Faculty of MedicineUniversiti Kebangsaan Malaysia Medical CentreKuala LumpurMalaysia
  2. 2.UKM Medical Molecular Biology Institute, National University of MalaysiaKuala LumpurMalaysia
  3. 3.Cell Therapy CenterUniversiti Kebangsaan Malaysia Medical CentreKuala LumpurMalaysia
  4. 4.Department of Medical Science II, Faculty of Medicine and Health ScienceIslamic Science University of MalaysiaKuala LumpurMalaysia
  5. 5.National Blood CentreKuala LumpurMalaysia

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