Posts Categorized: Part 05: CHROMOSOMES

Role of GABA Receptors for synaptic plasticity and memory in Down syndrome

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Altered GABAergic transmission through Cl–-permeable GABAA receptors (GABAARs) is known to contribute to learning and memory deficits in Down syndrome mouse models. In this study, GABAAR signaling was found to be excitatory rather than inhibitory, and the reversal potential for GABAAR-driven Cl– currents (ECl) was shifted toward more positive potentials in the hippocampi of adult Down syndrome mice. Hippocampal expression of […]

Synaptic deficits in neurons from 22q13 deletion syndrome patients is restored by SHANK3 and IGF1

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Microdeletion of 22q13 region encompassing SHANK3 gene and rare heterozygous mutations in SHANK3 have been associated with neurodevelopmental disorder Phelan–McDermid syndrome (PMDS), autism spectrum disorders (ASDs), non-syndromic intellectual disability, and schizophrenia. However, the cellular and molecular phenotypes resulting from SHANK3 haploinsufficiency in human neurons are unknown. In this study, induced pluripotent stem (iPS) cells were generated from individuals with PMDS […]

CPEB1 depletion ameliorates fragile X syndrome

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Fragile X syndrome (FXS) is caused by transcriptional silencing of FMR1 encoding the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element–binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, […]

Trisomy 21 correction by XIST-mediated silencing

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A paper recently published in Nature reports silencing of one chromosome 21 in Down syndrome cells.  Using genome editing with zinc finger nucleases, the authors inserted an inducible XIST (the X-inactivation gene) on chromosome 21 in Down syndrome pluripotent stem cells. The XIST non-coding RNA coated chromosome 21 and triggered stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation […]

Loss of SNX27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down syndrome

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A recent paper in Nature Medicine showed that Down syndrome brains have reduced expression of Sorting nexin 27 (SNX27) and CCAAT/enhancer binding protein beta (C/EBP beta) and identified C/EBP beta as a transcription factor for SNX27. Down syndrome results in overexpression of miR-155, a chromosome 21–encoded microRNA that negatively regulates C/EBP beta, thereby reducing SNX27 expression. SNX27 is a brain-enriched […]

Discovery of a long noncoding transcript coating the active X chromosome

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X-chromosome inactivation (XCI) in mammals relies on XIST, a long noncoding transcript that coats and silences the X chromosome in cis.  Vallot et al. have discovered a long noncoding RNA, XACT, that is expressed from and coats the active X chromosome in human pluripotent cells. In the absence of XIST, XACT is expressed from both X […]

Microdeletion 17q21.31 syndrome


In the September 2006 issue of Nature Genetics, three groups identify a new microdeletion syndrome (microdeletion 17q21.31). The major clinical features of this syndrome are severe hypotonia and moderate mental retardation See the News and Views article by James R. Lupski: Nat Genet. 2006 Sep;38(9):974-6. Genome structural variation and sporadic disease traits. Lupski JR. James […]