A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus
David Pellerin1,2, Giulia F Del Gobbo3, Madeline Couse4
1Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Quebec, Canada.
Abstract:
The factors driving or preventing pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a common 5'-flanking variant in 70.34% of alleles analyzed (3,463/4,923) that represents the phylogenetically ancestral allele and is present on all major haplotypes. This common sequence variation is present nearly exclusively on nonpathogenic alleles with fewer than 30 GAA-pure triplets and is associated with enhanced stability of the repeat locus upon intergenerational transmission and increased Fiber-seq chromatin accessibility.
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