A5005540720- Prenatal Screening and Diagnostics
- Hemoglobinopathies and Related Disorders
- Genomic variations and chromosomal abnormalities
- Parvovirus B19 Infection Studies
- Genetic Neurodegenerative Diseases
- Congenital Anomalies and Fetal Surgery
- Iron Metabolism and Disorders
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
- Hemophilia Treatment and Research
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Blood groups and transfusion
- Fetal and Pediatric Neurological Disorders
- Neurogenetic and Muscular Disorders Research
- CRISPR and Genetic Engineering
- Autism Spectrum Disorder Research
- Pediatric health and respiratory diseases
- Genetics and Neurodevelopmental Disorders
- Blood Coagulation and Thrombosis Mechanisms
- Inhalation and Respiratory Drug Delivery
- Cystic Fibrosis Research Advances
- Renal and related cancers
- Metabolism and Genetic Disorders
- DNA Repair Mechanisms
National University of Singapore
2001-2025
National University Health System
2010-2025
National University Hospital
2001-2012
Combined preimplantation genetic testing of aneuploidy (PGT-A) and monogenic disease (PGT-M) can be achieved through PCR-based whole genome amplification (WGA) next-generation sequencing (NGS). However, pathogenic variant detection is usually indirectly single nucleotide polymorphism haplotyping, as direct variants not always possible. We evaluated whether isothermal WGA was suitable for combined PGT-A PGT-M that also permitted repeat expansions large deletions, in addition to indirect...
Abstract Background Current strategies for preimplantation genetic testing aneuploidy or structural rearrangements (PGT-A/SR) rely mainly on next-generation sequencing (NGS) and microarray platforms, which are robust but require expensive instrumentation. We explored the suitability of third-generation single-molecule as a PGT-A/SR screening platform both segmental imbalance. Methods Single-cell multicell replicates from aneuploid segmentally unbalanced cell lines (n = 208) were...
To develop a single-tube multi-marker assay for improved preimplantation genetic diagnosis (PGD) of deletional and/or non-deletional Hb Bart's hydrops fetalis syndrome, providing haplotype confirmation status, and maximization linkage informativity.We performed in silico mining to identify novel microsatellites within 1 Mb flanking the alpha-globin gene cluster, optimized combining detection α(0) -thalassemia deletions with analysis. We validation on 100 single cells prior clinical PGD...
Preimplantation genetic testing for the monogenic disorder (PGT-M) spinal muscular atrophy (SMA) is significantly improved by supplementation of SMN1 deletion detection with marker-based linkage analysis. To expand availability informative markers PGT-M SMA, we identified novel non-duplicated and highly polymorphic microsatellite closely flanking SMN2 duplicated region. Six within 0.5 Mb 1.7 region containing (SMA6863, SMA6873, SMA6877, SMA7093, SMA7115, SMA7120) seven established (D5S1417,...
Beta (β)-thalassemia is one of the most common monogenic diseases worldwide. Affected pregnancies can be avoided through preimplantation genetic diagnosis (PGD), which commonly involves customized assays to detect different combinations β-globin (HBB) gene mutations present in couples, conjunction with linkage analysis flanking microsatellite markers. Currently, limited number reported closely linked markers hampers their utility indirect linkage-based PGD for this disorder. To increase...
Pre-implantation genetic diagnosis is used to analyse pre-implantation stage embryos or oocytes for defects, generally severe Mendelian disorders and chromosome abnormalities. New but controversial indications include identifying human leukocyte antigen compatible suitable as donor, sex selection adult-onset disorders, particularly cancer. screening a variant of improve outcomes in-vitro fertilisation. Array comparative genomic hybridisation replacing fluorescence in-situ aneuploidy...
Since the 1950s, a strong correlation between high carrier rates for β-thalassemia mutations and selective survival advantage in tropical subtropical 'malarial belt' regions has been established. Due to relatively more complex genetics of α-thalassemia, similar relationship was demonstrated α-globin gene only from 1980s, with both single- double-α-globin deletions prevalent malarial belt. Mechanistically, single-α-globin arise non-allelic recombination homologous α1 (HBA1) α2 (HBA2) globin...
Abstract Huntington disease (HD) is a lethal neurodegenerative disorder caused by expansion of CAG repeat within the huntingtin ( HTT ) gene. Disease prevention can be facilitated preimplantation genetic testing for this monogenic (PGT-M). We developed strategy HD PGT-M, involving whole genome amplification (WGA) followed combined triplet-primed PCR (TP-PCR) detection and multi-microsatellite marker genotyping haplotype phasing. The was validated tested pre-clinically in simulated PGT-M case...
Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a neurodegenerative disorder caused by the ATXN3 CAG repeat expansion. Preimplantation genetic testing for monogenic disorders (PGT-M) of SCA3/MJD should include reliable expansion detection coupled with high-risk allele determination using informative linked markers. One couple underwent PGT-M combining (CAG)n triplet-primed PCR (TP-PCR) customized linkage-based risk genotyping on whole-genome-amplified trophectoderm cells....
Abstract Background Hemophilia A (HEMA) is an X-linked bleeding disorder caused by reduced/absent coagulation factor VIII expression, as a result of pathogenic variants in the F8 gene. Preimplantation prevention HEMA should ideally include direct variant detection, complemented linkage analysis flanking markers to identify high-risk allele. Linkage particularly indispensable when cannot be detected directly or identified. This study evaluated suitability panel intragenic and extragenic short...