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

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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.

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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

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Acknowledgements

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

Funding

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

Author information

Authors and Affiliations

  1. Hematology Unit, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia

    Wui Chuen Chia, Noor Farisah Abdul Razak, Hafiza Alauddin, Raja Zahratul Azma Raja Sabudin & Noor Hamidah Hussin

  2. UKM Medical Molecular Biology Institute, National University of Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia

    Tze Sean Khoo

  3. Cell Therapy Center, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia

    S Fadilah S. Abdul Wahid

  4. Department of Medical Science II, Faculty of Medicine and Health Science, Islamic Science University of Malaysia, Kuala Lumpur, Malaysia

    Ainoon Othman

  5. National Blood Centre, Jalan Tun Razak, Titiwangsa, 50400, Kuala Lumpur, Malaysia

    Roshida Hassan

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

Corresponding author

Correspondence to Noor Hamidah Hussin.

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

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The authors declare that they have no conflict of interest.

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Chia, W.C., Khoo, T.S., Abdul Wahid, S.F.S. et al. Multiplex STR panel for assessment of chimerism following hematopoietic stem cell transplantation (HSCT). Ann Hematol 98, 1279–1291 (2019). https://doi.org/10.1007/s00277-019-03626-w

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