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| Status |
Public on May 08, 2024 |
| Title |
Altered chromatin topologies caused by balanced chromosomal translocation lead to central iris hypoplasia [Cut & Tag] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| 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.
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| Overall design |
Cleavage Under Targets and Tagmentation (CUT&Tag) for the histone modification H3K27ac in the induced pluripotent stem cells (iPSCs) from one patient and one normal control.
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| Citation(s) |
38871723 |
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| Submission date |
May 03, 2024 |
| Last update date |
Jun 28, 2024 |
| Contact name |
Qingjiong Zhang |
| E-mail(s) |
zhangqji@mail.sysu.edu.cn
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| Phone |
13609718372
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| Organization name |
Zhongshan Ophthalmic Center
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| Street address |
Sun Yat-sen University
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510060 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1107487 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE266513_RAW.tar |
425.0 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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