Arnold S C Tan

National University Health System, Singapore

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Publications (10)21.41 Total impact

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    ABSTRACT: Since the 1950s, a strong correlation between high carrier rates for β-thalassemia mutations and selective survival advantage in tropical and sub-tropical "malarial belt" regions has been established. Due to the relatively more complex genetics of α-thalassemia, a similar relationship was demonstrated for α-globin gene mutations only from the 1980s, with both single and double α-globin gene deletions prevalent in the malarial belt. Mechanistically, the single α-globin gene deletions arise from non-allelic recombination between the homologous α1 (HBA1) and α2 (HBA2) globin genes. Compared to the -α(3.7) and ααα(anti3.7) rightward crossover alleles, much less is known about the -α(4.2) and ααα(anti4.2) leftward crossover alleles. We performed a survey of 1,285 unselected cord blood samples from the 3 major ethnic groups in Singapore. Overall, the frequency of the -α(3.7) deletion was significantly higher than its reciprocal ααα(anti3.7) triplication, consistent with positive selection for the -α(3.7) single-gene deletion. In marked contrast, there was no significant difference in frequency between the -α(4.2) and reciprocal ααα(anti4.2) alleles, suggesting the absence of positive selection for the -α(4.2) single-gene deletion. The similar ααα(anti3.7) and ααα(anti4.2) allele frequencies also suggested that the crossover rates at X- and Z-homology boxes are similar. Taken together, these observations suggest a differential positive selection for the -α(3.7) and -α(4.2) alleles within the same population. Further population and biological studies may be required to explain these current observations. © 2013 John Wiley & Sons A/S.
    European Journal Of Haematology 01/2013; · 2.55 Impact Factor
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    ABSTRACT: Introduction: We aimed to develop and implement a short tandem repeat (STR) polymerase chain reaction alternative to fluorescence in situ hybridisation (FISH) for the preimplantation genetic diagnosis (PGD) of chromosomal translocations. Methods: Selected informative STRs located on translocated arms of relevant chromosomes were used to discriminate between normal and unbalanced chromosome states in each embryo. Results: PGD cycles were performed on five couples where one spouse carried a balanced translocation. 27 embryos were analysed, of which 12 were normal/balanced, 12 were abnormal/unbalanced and three were indeterminate. Four PGD cycles proceeded to embryo transfer, of which two led to pregnancy. The first pregnancy showed a normal male karyotype, and a healthy baby was delivered at term. A second pregnancy unexpectedly miscarried in the second trimester from unknown causes. Conclusion: STR analysis is a simple and suitable alternative to FISH for detecting unbalanced chromosomal states in preimplantation embryos.
    Singapore medical journal 10/2012; 53(10):648-54. · 0.63 Impact Factor
  • Boran Jiang, Arnold S C Tan, Samuel S Chong
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    ABSTRACT: Pre-implantation genetic diagnosis is used to analyse pre-implantation stage embryos or oocytes for genetic defects, generally for severe Mendelian disorders and chromosome abnormalities. New but controversial indications for pre-implantation genetic diagnosis include identifying human leukocyte antigen compatible embryos suitable as donor, sex selection and adult-onset disorders, particularly cancer. Pre-implantation genetic screening is a variant of pre-implantation genetic diagnosis to improve outcomes of in-vitro fertilisation. Array comparative genomic hybridisation is replacing fluorescence in-situ hybridisation for aneuploidy screening. Besides technical advancement of array platform, the success of pre-implantation genetic screening is strongly related to the embryonic biological nature of chromosomal mosaicism. Having been applied for more than 20 years, pre-implantation genetic diagnosis is recognised as an important alternative to prenatal diagnosis. Diagnosis from a single cell, however, remains a technically challenging procedure, and the risk of misdiagnosis cannot be eliminated.
    Best practice & research. Clinical obstetrics & gynaecology 08/2012; 26(5):551-9. · 1.87 Impact Factor
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    ABSTRACT: The high incidence of double-gene deletions in α-thalassaemia increases the risk of having pregnancies with homozygous α(0)-thalassaemia, the cause of the lethal haemoglobin (Hb) Bart's hydrops fetalis syndrome. Preimplantation genetic diagnosis (PGD) has played an important role in preventing such cases. However, the current gap-PCR based PGD protocol for deletional α-thalassaemia requires specific primer design for each specific deletion. A universal PGD assay applicable to all common deletional determinants of Hb Bart's hydrops fetalis syndrome has been developed. Microsatellite markers 16PTEL05 and 16PTEL06 within the α-globin gene cluster were co-amplified with a third microsatellite marker outside the affected region in a multiplex-PCR reaction and analysed by capillary electrophoresis. Eight informed couples at risk of having Hb Bart's hydrops fetalis were recruited in this study and all patients underwent standard procedures associated with IVF. A total of 47 embryos were analysed. Three pregnancies were achieved from three couples, with the births of two healthy babies and one ongoing pregnancy. This work has successfully adapted an earlier protocol and developed a simple and reliable single-cell assay applicable to PGD of Hb Bart's hydrops fetalis syndrome regardless of type of deletion. Alpha-thalassaemia is one of the most common inheritable disorders worldwide. It is a blood disorder that, in its lethal form caused by deletion of all four copies of the α-globin gene, results in the demise of the affected fetus, a condition referred to as haemoglobin (Hb) Bart's hydrops fetalis syndrome. Preimplantation genetic diagnosis (PGD) has played an important role in preventing such cases. Current PGD protocols for deletional α-thalassaemia utilize a strategy called gap-PCR, which requires the different assays for different deletion types. We have developed a universal PGD assay applicable to all common deletional determinants of Hb Bart's hydrops fetalis syndrome based on microsatellite marker analysis. Eight informed couples at risk of having Hb Bart's hydrops fetalis were recruited in this study and all patients underwent standard procedures associated with IVF. Forty-five embryos were analysed in total. Three pregnancies were achieved from three couples, with the births of two healthy babies and one pregnancy still ongoing. We have successfully adapted our earlier protocol and developed a simple and reliable single cell assay applicable to PGD of Hb Bart's hydrops fetalis syndrome regardless of the type of deletion.
    Reproductive biomedicine online 11/2010; 21(5):642-8. · 2.68 Impact Factor
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    ABSTRACT: We report the fi rst successful preimplantation genetic diagnosis (PGD) for Hb Bart's hydrops fetalis in Singapore, involving both fresh and frozen embryo replacement cycles. Two couples who were carriers of the Southeast Asian type double gene deletion (--(SEA) deletion carriers) requested for PGD. Couple A had 2 previous affected pregnancies, while couple B have a child of unknown genotypic status. One PGD cycle was performed for each couple. The --(SEA) deletion was detected using a gap-PCR strategy. Couple A had 1 fresh-embryo replacement cycle while couple B underwent 2 frozen-embryo replacement cycles. Couple A achieved a twin pregnancy. Second trimester complications resulted in premature delivery, where 1 baby girl survived. Couple B achieved a singleton pregnancy resulting in delivery of a healthy baby boy. Genotype analysis of all babies confirmed the PGD results consistent with clinically unaffected status. We have successfully performed PGD to avoid Hb Bart's hydrops fetalis syndrome.
    Annals of the Academy of Medicine, Singapore 10/2009; 38(10):910-3. · 1.36 Impact Factor
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    ABSTRACT: We report on the first successful preimplantation genetic diagnosis (PGD) in Singapore. A couple who are beta-thalassaemia carriers and have an affected daughter requested for PGD. Two cycles of PGD were performed on the couple. Beta-thalassaemia mutations were detected using a nested PCR and minisequencing strategy, and unaffected embryos were selected for transfer. A singleton pregnancy was achieved in the second PGD cycle, resulting in the birth of a healthy baby boy with carrier genotype. This case report documents the first successful PGD in Singapore, involving a couple at-risk of transmitting beta-thalassaemia major.
    Annals of the Academy of Medicine, Singapore 09/2009; 38(8):720-3. · 1.36 Impact Factor
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    ABSTRACT: This study aimed to evaluate a rapid molecular carrier screening strategy for beta-thalassemia. Allele-specific PCR was combined with amplicon detection by dissociation curve analysis of SYBR Green I fluorescence in a single step. The presence of a particular mutation results in the amplification of a mutation-specific product and the dissociation temperature of each amplicon was highly reproducible. Homogeneous allele-specific PCR amplification and detection of multiple beta-globin mutations can serve as a rapid and inexpensive carrier screening tool.
    Clinical Biochemistry 04/2007; 40(5-6):427-30. · 2.45 Impact Factor
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    ABSTRACT: Williams syndrome (WS) is a rare but well recognised neurodevelopmental disease affecting the connective tissue and the central nervous system. Many patients are identified through the presence of dysmorphic features and associated cardiac abnormalities. Klinefelter syndrome (KS) is associated with gynaecomastia, small testes, azoospermia and elevated gonadotropin levels. They are recognised in the second decade of life by their tall stature and delay in pubertal development. A combination of constitutive WS and KS has yet to be described. We report a child with these genetic aberrations, highlighting the clinical characteristics of such an individual. The manifestations and interactions of both conditions are also discussed.
    Annals of the Academy of Medicine, Singapore 01/2007; 35(12):901-4. · 1.36 Impact Factor
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    Clinical Chemistry 04/2005; 51(3):641-4. · 7.15 Impact Factor
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    Wen Wang, Arnold S. C. Tan