Tissue-specific and repeat length-dependent somatic instability of the X-linked dystonia parkinsonism-associated CCCTCT repeat
The length of a CCCTCT repeat within the SINE-VNTR-Alu retrotransposon associated with X-linked dystonia-parkinsonism (XDP) is inversely correlated with the age of disease onset. Here, the Wheeler lab investigated the instability of this repeat. Findings reveal:1) length-dependent and expansion-biased instability, with greater expansions in brain than in blood; 2) brain region-specific patterns of expansion that are broadly similar to those of the Huntington’s disease CAG repeat; 3) evidence that CCCTCT expansion propensity may be modified by local chromatin structure. The data support a role for CCCTCT somatic expansion underlying the rate of XDP onset.
Read more in Acta Neuropathologica Communications.
December 5, 2022
Publication
The Center for Genomic Medicine (CGM) comprises one of the largest and most vibrant hubs of genomic medicine research in the world. The CGM includes 46 faculty collaborating to define the ‘genomic medicine cycle’ – which envisages a genomics community seeking to advance research from basic genomics research to ultimately using genome information for diagnostics and targeted therapeutics. All of our investigators are faculty at Harvard Medical School, and many members of our community are also investigators at the Broad Institute of Harvard and MIT.
