Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping.

ABSTRACT:

Background

Fuchs endothelial corneal dystrophy (FECD) is the most common repeat-mediated disease in humans. It exclusively affects corneal endothelial cells (CECs), with ≤81% of cases associated with an intronic TCF4 triplet repeat (CTG18.1). Here, we utilise optical genome mapping (OGM) to investigate CTG18.1 tissue-specific instability to gain mechanistic insights.

Methods

We applied OGM to a diverse range of genomic DNAs (gDNAs) from patients with FECD and controls (n = 43); CECs, leukocytes and fibroblasts. A bioinformatics pipeline was developed to robustly interrogate CTG18.1-spanning DNA molecules. All results were compared with conventional polymerase chain reaction-based fragment analysis.

Findings

Analysis of bio-samples revealed that expanded CTG18.1 allele

SUBMITTER: Zarouchlioti C 

PROVIDER: S-EPMC11419830 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature