Vall d'Hebron Talks by VHIR 'A transposase-derived gene required for human brain development'

 Vall d'Hebron Talks by VHIR
  Sala d’actes de la planta baixa de l’Hospital General — See in map
08/10/2024
08/10/2024 -- From 15:00h to 16:00h
Organize :
Vall d'Hebron Institut de Recerca (VHIR)
Modality: In person and online
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Speaker: Luz Juebierre. Research Associate at Memorial Sloan Kettering Cancer Center

Vertebrate brain development is associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood. DNA transposable elements and transposase-derived genes could contribute to DNA breaks and somatic genome rearrangements, however their contributions to brain development are largely unknown. PiggyBac Transposable Element Derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase-derived gene with retained nuclease activity in human cells. We identified five unrelated consanguineous families with PGBD5 mutations using GeneMatcher. Affected individuals presented with disorder of intellectual disability, movement and seizures. In mice, Pgbd5 is required for the developmental induction of post-mitotic DNA breaks and recurrent somatic brain genome rearrangements. Single-nuclei RNA and ATAC sequencing of cerebral cortex showed that loss of Pgbd5 leads to aberrant differentiation and gene expression of distinct neuronal populations, including specific types of glutamatergic neurons, which can explain the features of PGBD5 deficiency in humans. Thus, PGBD5 is a transposase-derived gene required for brain development in mammals. 

Host: Miguel Segura, Main researcher - Childhood Cancer and Blood Disorders (VHIR)

 

 

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