A5043605363- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Pluripotent Stem Cells Research
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Biochemical effects in animals
- RNA modifications and cancer
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Curcumin's Biomedical Applications
- Genomic variations and chromosomal abnormalities
UConn Health
2020-2024
University of Connecticut
2020-2024
Farmington Community Library
2023
Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder caused by maternal duplications of this region. Autism and epilepsy are key features Dup15q. UBE3A, which encodes an E3 ubiquitin ligase, likely major driver Dup15q because UBE3A the only imprinted gene expressed solely from allele. Nevertheless, exact role has not been determined. To establish whether overexpression required for neuronal deficits, we generated isogenic control line patient-derived induced...
Abstract Loss of UBE3A expression, a gene regulated by genomic imprinting, causes Angelman syndrome (AS), rare neurodevelopmental disorder. The encodes an E3 ubiquitin ligase with three known protein isoforms in humans. Studies mouse suggest that the human may have differences localization and neuronal function. A recent case study reported mild AS phenotypes individuals lacking one specific isoform. Here we used CRISPR/Cas9 to generate isogenic embryonic stem cells (hESCs) lack individual...
Abstract Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity. This disorder caused the absence of paternally expressed gene products from chromosome 15q11–q13. We previously demonstrated that knocking out ZNF274, a Kruppel-associated box-A-domain zinc finger protein capable recruiting epigenetic machinery to deposit H3K9me3 repressive histone modification, can activate expression normally silent maternal allele SNORD116 in neurons...
Effort-related choice tasks are used for studying depressive motivational symptoms such as anergia/fatigue. These studies investigated the ability of dietary supplement curcumin to reverse low-effort bias induced by monoamine storage blocker tetrabenazine. Tetrabenazine shifted effort-related in rats, decreasing high-effort lever pressing but increasing chow intake. The effects tetrabenazine were reversed oral ingestion (80.0–160.0 mg/kg) and infusions into cerebral ventricles (2.0–8.0 μg)....
Abstract Angelman Syndrome (AS) and Prader-Willi (PWS), two distinct neurodevelopmental disorders, result from loss of expression imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either maternal or paternal allele, respectively. Each occurs at an approximate incidence 1/15,000 to 1/30,000 live births has range debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools understand human-relevant...
Angelman syndrome (AS) and Prader-Willi (PWS), two distinct neurodevelopmental disorders, result from loss of expression imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either maternal or paternal allele, respectively. Each occurs at an approximate incidence 1/15,000 to 1/30,000 live births has range debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools understand human-relevant gene...
Abstract Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function the maternally inherited UBE3A allele. In neurons, paternal allele silenced in cis long noncoding RNA, UBE3A-ATS . Unsilencing reducing promising therapeutic approach for treatment AS. Here we show that targeted cleavage using antisense oligonucleotides (ASOs) restores and rescues electrophysiological phenotypes human AS neurons. We demonstrate results termination its transcription displacement...
Abstract Loss of UBE3A expression, a gene regulated by genomic imprinting, causes Angelman Syndrome (AS), rare neurodevelopmental disorder. The encodes an E3 ubiquitin ligase with three known protein isoforms in humans. Studies mouse suggest that the human may have differences localization and neuronal function. A recent case study reported mild AS phenotypes individuals lacking one specific isoform. Here we used CRISPR/Cas9 to generate isogenic embryonic stem cells (hESCs) lack individual...
Abstract Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder caused by maternal duplications of this region. Autism and epilepsy are key features Dup15q, but affected individuals also exhibit intellectual disability developmental delay. UBE3A , the gene encoding ubiquitin protein ligase E3A, likely major driver Dup15q because with maternal, not paternal 15q have disorder, only imprinted expressed solely from allele in mature neurons. Nevertheless, exact role...
Abstract Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay, and hyperphagia/obesity. This disorder caused the absence of paternally-expressed gene products from chromosome 15q11-q13. We previously demonstrated that knocking out ZNF274, a KRAB-domain zinc finger protein capable recruiting epigenetic machinery to deposit H3K9me3 repressive histone modification, can activate expression normally silent maternal allele SNORD116 in neurons derived PWS iPSCs....