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

Document Type

Article

Publication Date

7-2024

Identifier

DOI: 10.1038/s41588-024-01808-5

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.

Journal Title

Nature genetics

Volume

56

Issue

7

First Page

1366

Last Page

1370

MeSH Keywords

Fibroblast Growth Factors; Humans; Alleles; Haplotypes; Genetic Variation; Genetic Loci

Keywords

Fibroblast Growth Factors; Alleles; Haplotypes; Genetic Variation; Genetic Loci

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