Siong-Chuan, Samuel Chong
Postgraduate:
Main Appointment:
Joint Appointments:
Research Fields:
Research Areas:
Research Fields:
- STEMM – Science, Technology, Engineering, Mathematics, Medical Sciences
Research Keywords:
- Preimplantation Genetic Testing
- Diagnostic Development
- Inherited Disorders
- Mental Retardation
- Thalassemia
Current Appointments:
Brief Description of Research:
For couples at risk of conceiving offspring affected with a Mendelian or chromosomal disorder, preimplantation genetic testing offers the promise of embarking on a clinically unaffected pregnancy, and birth of a healthy baby, through the uterine transfer of only genetically unaffected embryos. Our diagnostic development group is working on innovative strategies for simplified preimplantation genetic testing of common and rare monogenic disorders such as alpha- and beta-thalassemia, spinal muscular atrophy, haemophilia A, and repeat expansion disorders such as fragile X syndrome, myotonic dystrophy, Huntington disease and the spinocerebellar ataxias. Advances in single cell genomic methodologies have also enabled comprehensive chromosome screening to identify only euploid preimplantation embryos for uterine transfer to reduce time to pregnancy and to improve healthy live-birth success. Development of novel strategies for preimplantation genetic screening of chromosomal aberrations using second and third generation sequencing platforms is in progress. One complication confronting accurate clinical preimplantation genetic testing has been the observation of chromosomal mosaicism in preimplantation embryos. We are interested to determine the prevalence of mosaic embryos, and degree of chromosomal mosacism within an embryo, as they are critical to improving post-test genetic counseling of patients. We are also interested in studying gene expression in the inner cell mass and trophectoderm of aneuploid embryos to gain insights into the relationship between aneuploidy and implantation failure, through correlation between cell-specific aneuploidies and their transcriptome signatures.
Total Number of Publications:
Five Representative Publications:
Zhao M, Chen M, Lee CG, Chong SS. Identification of novel microsatellite markers <1 Mb from the HTT CAG repeat and development of a single-tube tridecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of Huntington disease. Clinical Chemistry 62(8):1096-105 (2016). https://doi.org/10.1373/clinchem.2016.255711.
Chen M, Zhao M, Lee CG, Chong SS. Identification of microsatellite markers <1 Mb from the FMR1 CGG repeat and development of a single-tube tetradecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of fragile X syndrome. Genetics in Medicine 18(9):869-75 (2016). https://doi.org/10.1038/gim.2015.185
Rajan-Babu IS, Lian M, Tran AH, Dang TT, Le HT-M, Thanh MN, Lee CG, Chong SS. Defining the performance parameters of a rapid screening tool for FMR1 CGG-repeat expansions based on direct triplet-primed PCR and melt curve analysis. Journal of Molecular Diagnostics 18(5):719-30 (2016). https://doi.org/10.1016/j.jmoldx.2016.05.002.
Lian M, Law HY, Lee CG, Chong SS. Defining the performance parameters of a rapid screening tool for myotonic dystrophy type 1 based on triplet-primed PCR and melt curve analysis. Expert Review of Molecular Diagnostics 16(11):1221-32 (2016). https://doi.org/10.1080/14737159.2016.1241145.
Lian M, Zhao M, Lee CG, Chong SS. Single-tube dodecaplex PCR panel of polymorphic microsatellite markers closely linked to the DMPK CTG repeat for preimplantation genetic diagnosis of myotonic dystrophy type 1. Clinical Chemistry 63(6):1127-40 (2017). https://doi.org/10.1373/clinchem.2017.271528.
Zhao M, Chen M, Tan AS, Cheah FS, Mathew J, Wong PC, Chong SS. Single-tube tetradecaplex panel of highly polymorphic microsatellite markers <1 Mb from F8 for simplified preimplantation genetic diagnosis of haemophilia A. Journal of Thrombosis and Haemostasis 15:1473-83 (2017). https://doi.org/10.1111/jth.13685.
Rajan-Babu IS, Lian M, Cheah FS, Chen M, Tan AS, Prasath EB, Loh SF, Chong SS. FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome. Expert Reviews in Molecular Medicine 19:e10 (2017). https://doi.org/10.1017/erm.2017.10.
Tan VJ, Lian M, Faradz SMH, Winarni TI, Chong SS. A single common assay for robust and rapid fragile X mental retardation syndrome screening from dried blood spots. Frontiers in Genetics 9:582 (2018). https://doi.org/10.3389/fgene.2018.00582.
Rajan-Babu IS, Chong SS. Triplet-repeat primed PCR and capillary electrophoresis for characterizing the fragile X mental retardation 1 CGG repeat hyperexpansions. Methods in Molecular Biology 1972:199-210 (2019). https://doi.org/10.1007/978-1-4939-9213-3_14.
Lian M, Lee CG, Chong SS. Robust preimplantation genetic testing strategy for myotonic dystrophy type 1 by bidirectional triplet-primed PCR combined with multi-microsatellite haplotyping following whole genome amplification. Frontiers in Genetics 10:589 (2019). https://doi.org/10.3389/fgene.2019.00589.
Zhao M, Lian M, Cheah FSH, Tan AS, Agarwal A, Chong SS. Identification of novel microsatellite markers flanking the SMN1 and SMN2 duplicated region and inclusion into a single-tube tridecaplex panel for haplotype-based preimplantation genetic testing of spinal muscular atrophy. Frontiers in Genetics 10:1105 (2019). https://doi.org/10.3389/fgene.2019.01105.
Zhao M, Cheah FS, Tan AS, Lian M, Phang GP, Agarwal A, Chong SS. Robust preimplantation genetic testing of Huntington disease by combined triplet-primed PCR analysis of the HTT CAG repeat and multi-microsatellite haplotyping. Scientific Reports 9:16481 (2019). https://doi.org/10.1038/s41598-019-52769-3.
Lian M, Zhao M, Phang GP, Yoon C-S, Lee CG, Law H-Y, Chong SS. Rapid molecular screen of spinocerebellar ataxia types 1, 2, and 3 by triplet-primed PCR and melting curve analysis. Journal of Molecular Diagnostics 23:565-76 (2021). https://doi.org/10.1016/j.jmoldx.2021.01.012.
Liu T, Wang FS, Cheah FSH, Gu Y, Shaw M, Law H-Y, Tay SKH, Lee CG, Nelson DL, Gecz J, Chong SS. Simultaneous screening of the FRAXA and FRAXE loci for rapid detection of FMR1 CGG and/or AFF2 CCG repeat expansions by triplet-primed PCR. Journal of Molecular Diagnostics 23:941-51 (2021). https://doi.org/10.1016/j.jmoldx.2021.04.015
Rajan-Babu IS, Phang G-P, Law H-Y, Lee CG, Chong SS. High-throughput methylation-specific triplet-primed PCR and melting curve analysis for selective and reliable identification of actionable FMR1 genotypes. Journal of Molecular Diagnostics 24:241-52 (2022). https://doi.org/10.1016/j.jmoldx.2021.11.007
Lian M, Limwongse C, Yoon C-S, Lee CG, Law H-Y, Chong SS. Single-tube screen for rapid detection of repeat expansions in seven common spinocerebellar ataxias. Clinical Chemistry 68:794–802 (2022). https://doi.org/10.1093/clinchem/hvac011
My Research Videos:
Top 5 Publications:
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
Journals Published:
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
- Lorem ipsum dolor sit amet
Appointments
Education
Research Areas
- Preimplantation Genetic Testing
- Diagnostic Development
- Inherited Disorders
- Mental Retardation
- Thalassemia
Research Description
For couples at risk of conceiving offspring affected with a Mendelian or chromosomal disorder, preimplantation genetic testing offers the promise of embarking on a clinically unaffected pregnancy, and birth of a healthy baby, through the uterine transfer of only genetically unaffected embryos. Our diagnostic development group is working on innovative strategies for simplified preimplantation genetic testing of common and rare monogenic disorders such as alpha- and beta-thalassemia, spinal muscular atrophy, haemophilia A, and repeat expansion disorders such as fragile X syndrome, myotonic dystrophy, Huntington disease and the spinocerebellar ataxias. Advances in single cell genomic methodologies have also enabled comprehensive chromosome screening to identify only euploid preimplantation embryos for uterine transfer to reduce time to pregnancy and to improve healthy live-birth success. Development of novel strategies for preimplantation genetic screening of chromosomal aberrations using second and third generation sequencing platforms is in progress. One complication confronting accurate clinical preimplantation genetic testing has been the observation of chromosomal mosaicism in preimplantation embryos. We are interested to determine the prevalence of mosaic embryos, and degree of chromosomal mosacism within an embryo, as they are critical to improving post-test genetic counseling of patients. We are also interested in studying gene expression in the inner cell mass and trophectoderm of aneuploid embryos to gain insights into the relationship between aneuploidy and implantation failure, through correlation between cell-specific aneuploidies and their transcriptome signatures.
Research Videos
Selected Publications
Zhao M, Chen M, Lee CG, Chong SS. Identification of novel microsatellite markers <1 Mb from the HTT CAG repeat and development of a single-tube tridecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of Huntington disease. Clinical Chemistry 62(8):1096-105 (2016). https://doi.org/10.1373/clinchem.2016.255711.
Chen M, Zhao M, Lee CG, Chong SS. Identification of microsatellite markers <1 Mb from the FMR1 CGG repeat and development of a single-tube tetradecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of fragile X syndrome. Genetics in Medicine 18(9):869-75 (2016). https://doi.org/10.1038/gim.2015.185
Rajan-Babu IS, Lian M, Tran AH, Dang TT, Le HT-M, Thanh MN, Lee CG, Chong SS. Defining the performance parameters of a rapid screening tool for FMR1 CGG-repeat expansions based on direct triplet-primed PCR and melt curve analysis. Journal of Molecular Diagnostics 18(5):719-30 (2016). https://doi.org/10.1016/j.jmoldx.2016.05.002.
Lian M, Law HY, Lee CG, Chong SS. Defining the performance parameters of a rapid screening tool for myotonic dystrophy type 1 based on triplet-primed PCR and melt curve analysis. Expert Review of Molecular Diagnostics 16(11):1221-32 (2016). https://doi.org/10.1080/14737159.2016.1241145.
Lian M, Zhao M, Lee CG, Chong SS. Single-tube dodecaplex PCR panel of polymorphic microsatellite markers closely linked to the DMPK CTG repeat for preimplantation genetic diagnosis of myotonic dystrophy type 1. Clinical Chemistry 63(6):1127-40 (2017). https://doi.org/10.1373/clinchem.2017.271528.
Zhao M, Chen M, Tan AS, Cheah FS, Mathew J, Wong PC, Chong SS. Single-tube tetradecaplex panel of highly polymorphic microsatellite markers <1 Mb from F8 for simplified preimplantation genetic diagnosis of haemophilia A. Journal of Thrombosis and Haemostasis 15:1473-83 (2017). https://doi.org/10.1111/jth.13685.
Rajan-Babu IS, Lian M, Cheah FS, Chen M, Tan AS, Prasath EB, Loh SF, Chong SS. FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome. Expert Reviews in Molecular Medicine 19:e10 (2017). https://doi.org/10.1017/erm.2017.10.
Tan VJ, Lian M, Faradz SMH, Winarni TI, Chong SS. A single common assay for robust and rapid fragile X mental retardation syndrome screening from dried blood spots. Frontiers in Genetics 9:582 (2018). https://doi.org/10.3389/fgene.2018.00582.
Rajan-Babu IS, Chong SS. Triplet-repeat primed PCR and capillary electrophoresis for characterizing the fragile X mental retardation 1 CGG repeat hyperexpansions. Methods in Molecular Biology 1972:199-210 (2019). https://doi.org/10.1007/978-1-4939-9213-3_14.
Lian M, Lee CG, Chong SS. Robust preimplantation genetic testing strategy for myotonic dystrophy type 1 by bidirectional triplet-primed PCR combined with multi-microsatellite haplotyping following whole genome amplification. Frontiers in Genetics 10:589 (2019). https://doi.org/10.3389/fgene.2019.00589.
Zhao M, Lian M, Cheah FSH, Tan AS, Agarwal A, Chong SS. Identification of novel microsatellite markers flanking the SMN1 and SMN2 duplicated region and inclusion into a single-tube tridecaplex panel for haplotype-based preimplantation genetic testing of spinal muscular atrophy. Frontiers in Genetics 10:1105 (2019). https://doi.org/10.3389/fgene.2019.01105.
Zhao M, Cheah FS, Tan AS, Lian M, Phang GP, Agarwal A, Chong SS. Robust preimplantation genetic testing of Huntington disease by combined triplet-primed PCR analysis of the HTT CAG repeat and multi-microsatellite haplotyping. Scientific Reports 9:16481 (2019). https://doi.org/10.1038/s41598-019-52769-3.
Lian M, Zhao M, Phang GP, Yoon C-S, Lee CG, Law H-Y, Chong SS. Rapid molecular screen of spinocerebellar ataxia types 1, 2, and 3 by triplet-primed PCR and melting curve analysis. Journal of Molecular Diagnostics 23:565-76 (2021). https://doi.org/10.1016/j.jmoldx.2021.01.012.
Liu T, Wang FS, Cheah FSH, Gu Y, Shaw M, Law H-Y, Tay SKH, Lee CG, Nelson DL, Gecz J, Chong SS. Simultaneous screening of the FRAXA and FRAXE loci for rapid detection of FMR1 CGG and/or AFF2 CCG repeat expansions by triplet-primed PCR. Journal of Molecular Diagnostics 23:941-51 (2021). https://doi.org/10.1016/j.jmoldx.2021.04.015
Rajan-Babu IS, Phang G-P, Law H-Y, Lee CG, Chong SS. High-throughput methylation-specific triplet-primed PCR and melting curve analysis for selective and reliable identification of actionable FMR1 genotypes. Journal of Molecular Diagnostics 24:241-52 (2022). https://doi.org/10.1016/j.jmoldx.2021.11.007
Lian M, Limwongse C, Yoon C-S, Lee CG, Law H-Y, Chong SS. Single-tube screen for rapid detection of repeat expansions in seven common spinocerebellar ataxias. Clinical Chemistry 68:794–802 (2022). https://doi.org/10.1093/clinchem/hvac011