A5086703396- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- Cancer-related cognitive impairment studies
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Digital Media and Visual Art
- Coleoptera Taxonomy and Distribution
- Molecular Biology Techniques and Applications
- Bacterial Genetics and Biotechnology
- Gene expression and cancer classification
- Congenital limb and hand anomalies
- Ferroptosis and cancer prognosis
- Genetic Neurodegenerative Diseases
Boston Children's Hospital
2019-2025
Harvard University
2019-2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2020-2025
Broad Institute
2019-2025
Boston Children's Museum
2024-2025
National Institute of Biological Sciences, Beijing
2014-2019
Peking Union Medical College Hospital
2017-2019
Chinese Academy of Medical Sciences & Peking Union Medical College
2017-2019
State Administration of Foreign Experts Affairs
2010
Abstract Splice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases 1 , but the systematic identification such remains challenge. Here we performed whole-genome sequencing analyses characterize variation in 235 (from 209 families) ataxia-telangiectasia, severely debilitating and life-threatening recessive disorder 2,3 yielding complete molecular diagnosis almost all individuals. We developed predictive taxonomy assess amenability...
Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism the brain other somatic tissues of an individual. However, distribution human-specific (L1Hs) insertions their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 from 20 postmortem five Rett patients matched controls. We identified validated L1Hs both...
The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASDs) remain unclear. In this study the whole exomes 2,361 families Simons Simplex Collection, we identified 1,248 putative pSNMs children 285 de novo SNPs with detectable parental mosaicism. Ultra-deep amplicon resequencing suggested a validation rate 51%. Analyses validated revealed that missense/loss-of-function (LoF) high mutant allele fraction (MAF≥ 0.2) contributed to ASD...
Postzygotic single-nucleotide mutations (pSNMs) have been studied in cancer and a few other overgrowth human disorders at whole-genome scale found to play critical roles. However, clinically unremarkable individuals, pSNMs never identified largely due technical difficulties lack of matched control tissue samples, thus the genome-wide characteristics remain unknown. We developed new Bayesian-based mosaic genotyper series effective error filters, using which we were able identify 17 SNM sites...
Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive neuronal loss and pathological accumulation of the misfolded proteins amyloid-β tau1,2. Neuroinflammation mediated microglia brain-resident macrophages plays a crucial role in AD pathogenesis1-5, though mechanisms which age, genes, other risk factors interact remain largely unknown. Somatic mutations accumulate with age lead to clonal expansion many cell types, contributing cancer non-cancer...
Heterozygous loss-of-function (LoF) variants in RFX3, a transcription factor known to play key roles ciliogenesis, result autism spectrum disorder (ASD) and neurodevelopmental delay. RFX binding motifs are also enriched upstream of genes found be commonly dysregulated transcriptomic analyses brain tissue from individuals with idiopathic ASD. Still, the precise functions RFX3 human is unknown. Here, we studied impact deficiency using iPSC-derived neurons forebrain organoids. Biallelic loss...
Changes in RNA splicing over the course of evolution have profoundly diversified functional landscape human genome. While DNA sequences proximal to intron-exon junctions are known be critical for splicing, impact distal intronic remains underexplored. Emerging evidence suggests that inverted pairs Alu elements can promote exon skipping by forming stem-loop structures. However, their prevalence and influence throughout remain unknown. Here, we present a systematic analysis across genome...
Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle. HCMV infection upregulates expression by enhancing both of L1-activating transcription factors, YY1 RUNX3, chromatin accessibility promoter regions. Increased expression,...
In most microarray assays, labeled cDNA molecules derived from reference and query RNA samples are co-hybridized to probes arrayed on a glass surface. Gene expression profiles then calculated for each gene based the relative hybridization intensities measured between two samples. The commonly used typically isolates single representative source (RNA-0) or pooled mixtures of plurality sources (RNA-p). Genomic DNA offers an alternative nucleic acid with number potential advantages, including...
ABSTRACT Purpose We describe a novel neurobehavioral syndrome of autism spectrum disorder, intellectual disability, and attention deficit/hyperactivity disorder associated with de novo or inherited deleterious variants in members the RFX family genes. genes are evolutionarily conserved transcription factors that act as master regulators central nervous system development ciliogenesis. Methods assembled cohort 36 individuals (from 31 unrelated families) mutations RFX3, RFX4 , RFX7 . their...
Abstract Background Alzheimer’s disease (AD), an age‐associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid‐β tau. While neuroinflammation, mediated microglia brain‐resident macrophages, plays a pivotal role in AD pathogenesis, intricate interactions among age, genes, other risk factors remain elusive. Somatic mutations, known to accumulate with instigate clonal expansion across diverse cell types,...
Abstract Mutations that occur in cells of the body, called somatic mutations, cause human diseases including cancer and some neurological disorders 1 . In a recent study published Nature, Lee et al. 2 (hereafter “the study”) reported copy number gains APP gene, known risk locus Alzheimer’s disease (AD), neurons AD-patients controls (69% vs 25% with at least one gain on average). The authors argue mechanism these was integration mRNA into genome, creating what they genomic cDNA (gencDNA). We...
Abstract Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism the brain other somatic tissues of an individual. However, distribution L1Hs (Human-specific LINE-1) insertions their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 from 20 postmortem five Rett patients matched controls. We identified validated...
ABSTRACT Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis -regulatory elements subsequently nominate candidate variants in the congenital dysinnervation disorders (CCDDs), set of altering cMN development. We generated epigenomic...