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Altered chromatin topologies caused by balanced chromosomal translocation lead to central iris hypoplasia [RNA-Seq]

GSE266515 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2024/05/08 Platform GPL11154
Summary
Despite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression.
Published in
Altered chromatin topologies caused by balanced chromosomal translocation lead to central iris hypoplasia
Sun W, Xiong D, Ouyang J et al. · Nature communications 2024 · PMID 38871723 · doi:10.1038/s41467-024-49376-w
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Also filed as BioProject PRJNA1107490 and SRA study SRP505650. Searching any of these in the dataset finder brings you back here.

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