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GLTD (gene-length-transcription-decline) with aging, most sensitive in neural tissue


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https://www.cell.com/trends/genetics/fulltext/S0168-9525(24)00027-1

An extremely long gene may render local genomic organization prone to fragility. This effect has been recently ascribed to topologically associating domains (TADs), which are 3D units of the genome packing adjacent genes. At average lengths of ∼300–900 kb in different cell types [55], a single TAD can accommodate multiple medium-sized genes but usually cannot completely contain even a single long gene in the megabase range. As a result, long genes often cross TAD boundaries, a feature that reportedly creates fragile sites [56]. Intronic expansion has promoted functional complexity and tissue specialization of genes that act in neurobiology. This may explain the extreme lengths of some neuronal and synaptic genes [57,58] and their possible contribution to the emergence of fragile sites, which can be seen as a double-edged sword.

Edited by Alex K Chen
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