A5091894111- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Metabolism and Genetic Disorders
- Genetic Associations and Epidemiology
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Genetic Neurodegenerative Diseases
- Coenzyme Q10 studies and effects
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- ATP Synthase and ATPases Research
- Genetic factors in colorectal cancer
- Biochemical Acid Research Studies
- Genetic Syndromes and Imprinting
- Genomic variations and chromosomal abnormalities
- Radiomics and Machine Learning in Medical Imaging
Agency for Science, Technology and Research
2025
Genome Institute of Singapore
2025
Nanyang Technological University
2021-2023
Institute for Biomedical Engineering
2012-2021
Bioengineering (Switzerland)
2012-2021
ETH Zurich
2012-2021
SIB Swiss Institute of Bioinformatics
2018
National University of Singapore
2012-2015
Abstract Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly Aβ 1–42 form, in brain. Mitochondrial dysfunction and impaired energy metabolism are important components AD pathogenesis. However, causal temporal relationships between them pathology remain unclear. Using novel C. elegans strain with constitutive neuronal expression that displays neuromuscular defects age-dependent behavioural reminiscent AD, we have...
Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation 9051 genomes representing East Asian, South and severely Austronesian-speaking Southeast ancestries. We observe disparate risk burden attributable to ancestry-specific recurrent variants identify individuals with specific ancestries discordant their self-reported ethnicity, mostly due cryptic admixture. About 27% of severe recessive disorder genes appreciable...
Disruption of mitochondrial metabolism and loss DNA (mtDNA) integrity are widely considered as evolutionarily conserved (public) mechanisms aging (López-Otín et al., Cell, 153, 2013 1194). Human is associated with in skeletal muscle mass function (Sarcopenia), contributing significantly to morbidity mortality. Muscle mtDNA integrity. In humans, clonally expanded deletions colocalize sites fiber breakage atrophy muscle. may therefore play an important, possibly causal role sarcopenia. The...
Deletion mutations within mitochondrial DNA (mtDNA) have been implicated in degenerative and aging related conditions, such as sarcopenia neuro-degeneration. While the precise molecular mechanism of deletion formation mtDNA is still not completely understood, genome motifs direct repeat (DR) stem-loop (SL) observed neighborhood breakpoints thus postulated to take part mutagenesis. In this study, we analyzed genomes from four different mammals: human, rhesus monkey, mouse rat, compared them...
Non D-loop direct repeats (DRs) in mitochondrial DNA (mtDNA) have been commonly implicated the mutagenesis of mtDNA deletions associated with neuromuscular disease and ageing. Further, these DRs hypothesized to put a constraint on lifespan mammals are under negative selection pressure. Using compendium 294 mammalian mtDNA, we re-examined relationship between species mutagenicity such DRs. Contradicting prevailing hypotheses, found no significant evidence that long-lived possess fewer...
Abstract Broad evidence support double-strand breaks (DSBs) as initiators of mitochondrial DNA (mtDNA) deletion mutations. But the mechanism DSB-induced deletions, including DSB repair pathway(s) involved, remains to be established. Here, we used hybridization thermodynamics analyze misalignment lengths surrounding breakpoints. Our analysis 9,655 previously reported mammalian mtDNA deletions and 1,307 novel Caenorhabditis elegans indicates a significant role 0–25bp misalignments, supporting...
Summary Disruption of mitochondrial metabolism and loss DNA (mtDNA) integrity are widely considered as evolutionarily conserved (public) mechanisms ageing (López-Otín et al. 2013). Human is associated with in skeletal muscle mass function (Sarcopenia), contributing significantly to morbidity mortality. Muscle mtDNA integrity. In humans, clonally expanded deletions co-localize sites fiber-breakage atrophy muscle. may therefore play an important, possibly causal role sarcopenia. The nematode...
Broad evidence in the literature supports double-strand breaks (DSBs) as initiators of mitochondrial DNA (mtDNA) deletion mutations. While misalignment during DSB repair is commonly proposed mechanism by which DSBs cause mutations, details such specific errors are still lacking. Here, we used hybridization thermodynamics to infer sequence lengths mtDNA misalignments that associated with deletions. We gathered and analyzed 9,921 previously reported breakpoints human, rhesus monkey, mouse,...