A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus.

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.

SUBMITTER: Pellerin D 

PROVIDER: S-EPMC11440897 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature