Imperial College London
Alternate

DrWeiCui

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2124wei.cui Website

 
 
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Location

 

1010Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{De:2023:10.26508/lsa.202201843,
author = {De, Vas M and Boulet, F and Joshi, SS and Garstang, MG and Khan, TN and Atla, G and Parry, D and Moore, D and Cebola, I and Zhang, S and Cui, W and Lampe, AK and Lam, WW and Genomics, England Research Consortium and Ferrer, J and Madapura, PM and Atanur, SS},
doi = {10.26508/lsa.202201843},
journal = {Life Science Alliance},
pages = {1--16},
title = {Regulatory de novo mutations underlying intellectual disability},
url = {http://dx.doi.org/10.26508/lsa.202201843},
volume = {6},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The genetic aetiology of a major fraction of patients with intellectual disability (ID) remains unknown. De novo mutations (DNMs) in protein-coding genes explain up to 40% of cases, but the potential role of regulatory DNMs is still poorly understood. We sequenced 63 whole genomes from 21 ID probands and their unaffected parents. In addition, we analysed 30 previously sequenced genomes from exome-negative ID probands. We found that regulatory DNMs were selectively enriched in fetal brain-specific enhancers as compared with adult brain enhancers. DNM-containing enhancers were associated with genes that show preferential expression in the prefrontal cortex. Furthermore, we identified recurrently mutated enhancer clusters that regulate genes involved in nervous system development (CSMD1, OLFM1, and POU3F3). Most of the DNMs from ID probands showed allele-specific enhancer activity when tested using luciferase assay. Using CRISPR-mediated mutation and editing of epigenomic marks, we show that DNMs at regulatory elements affect the expression of putative target genes. Our results, therefore, provide new evidence to indicate that DNMs in fetal brain-specific enhancers play an essential role in the aetiology of ID.
AU  - De,Vas M
AU  - Boulet,F
AU  - Joshi,SS
AU  - Garstang,MG
AU  - Khan,TN
AU  - Atla,G
AU  - Parry,D
AU  - Moore,D
AU  - Cebola,I
AU  - Zhang,S
AU  - Cui,W
AU  - Lampe,AK
AU  - Lam,WW
AU  - Genomics,England Research Consortium
AU  - Ferrer,J
AU  - Madapura,PM
AU  - Atanur,SS
DO  - 10.26508/lsa.202201843
EP  - 16
PY  - 2023///
SN  - 2575-1077
SP  - 1
TI  - Regulatory de novo mutations underlying intellectual disability
T2  - Life Science Alliance
UR  - http://dx.doi.org/10.26508/lsa.202201843
UR  - https://www.life-science-alliance.org/content/6/5/e202201843
UR  - http://hdl.handle.net/10044/1/102977
VL  - 6
ER  -
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