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Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic human-specific LINE-1 (L1Hs) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues. In Rett patients, somatic insertions were significantly depleted in exons-mainly contributed by long genes-than healthy controls, implying that cells carrying MECP2 mutations might be defenseless against a second exonic L1Hs insertion. We observed a significant increase of somatic L1Hs insertions in the brain compared with non-brain tissues from the same individual. Compared to germline insertions, somatic insertions were less sense-depleted to transcripts, indicating that they underwent weaker selective pressure on the orientation of insertion. Our observations demonstrate that somatic L1Hs insertions contribute to genomic diversity and MeCP2 dysfunction alters their genomic patterns in Rett patients.
This article was published in the following journal.
Name: PLoS genetics
To identify whether somatic mutations in alter N-glycan structures in human brain tissues and cause nonlesional focal epilepsy (NLFE) or mild malformation of cortical development (mMCD).
Malformations of cortical development are a frequent cause of drug-resistant Epilepsy and developmental delay. Hemimegalencephaly is a Malformation of cortical development characterized by enlargement...
Rett syndrome (RTT) is a rare congenital disorder which in most cases (95%) is caused by methyl-CpG binding protein 2 (MECP2) mutations. RTT is characterized by regression in global development, epile...
Neuronal connectivity in the cortex is determined by the laminar positioning of neurons. An important determinant of laminar positioning is likely to be the control of leading process behavior during ...
The biophysical features of neurons shape information processing in the brain. Cortical neurons are larger in humans than in other species, but it is unclear how their size affects synaptic integrati...
Increased brain glutamate and its NMDA receptors found in the brain of younger Rett syndrome (RTT) patients cause toxic damage to neurons (the brain's nerve cells), and contributing to EEG...
Introduction: Rett Syndrome is a neurodevelopmental disease that primarily affects girls. Clinically, patients are normal before six months to one and half years old, and then develop prog...
Rett syndrome (RTT) is a disorder in which the nervous system does not develop properly. RTT generally affects girls, but there are some boys who have been diagnosed with RTT. Symptoms of ...
This is a phase 2 , open label, dose escalating study of Lovastatin in Rett syndrome.
OBJECTIVES: I. Extend current knowledge of the phenotype and natural history of Rett syndrome (RS). II. Continue the search for a cytogenetic and/or DNA marker. III. Study the effects o...
Heterogeneous disorders of cortical malformation characterized by excessive and small fused gyri and shallow sulci of the CORTEX with abnormal cortical lamination. It is considered a malformation secondary to abnormal post-migrational development of the neurons during cerebral cortical development and is associated with EPILEPSY and learning difficulties.
Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions.
A calcium-binding protein that mediates calcium HOMEOSTASIS in KIDNEYS, BRAIN, and other tissues. It is found in well-defined populations of NEURONS and is involved in CALCIUM SIGNALING and NEURONAL PLASTICITY. It is regulated in some tissues by VITAMIN D.
EEG phase synchronization of the cortical brain region (CEREBRAL CORTEX).
Adjustment of BRAIN WAVES from two or more neuronal groups within or across a brain structure (e.g., cortical and limbic brain structures) to become uniform in EEG oscillation patterns in response to a stimulus. It is interpreted as a brain integration sign during many processes such as learning, memory, and perception and involves reciprocal neural connections.
Polymerase Chain Reaction (PCR)
PCR (Polymerase Chain Reaction) uses the ability of DNA polymerase (enzymes that create DNA molecules by assembling nucleotides, the building blocks of DNA. These enzymes are essential to DNA replication and usually work in pairs to create two ident...
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...