Imperial College London
Dr Ines Cebola

DrInesCebola

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer in Regulatory Genomics
 
 
 
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Contact

 

i.dos-santos-cebola Website

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Weedon:2014:10.1038/ng.2826,
author = {Weedon, MN and Cebola, I and Patch, A-M and Flanagan, SE and De, Franco E and Caswell, R and Rodríguez-Seguí, SA and Shaw-Smith, C and Cho, CH-H and Allen, HL and Houghton, JA and Roth, CL and Chen, R and Hussain, K and Marsh, P and Vallier, L and Murray, A and International, Pancreatic Agenesis Consortium and Ellard, S and Ferrer, J and Hattersley, AT},
doi = {10.1038/ng.2826},
journal = {Nature genetics},
pages = {61--64},
title = {Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.},
url = {http://dx.doi.org/10.1038/ng.2826},
volume = {46},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The contribution of cis-regulatory mutations to human disease remains poorly understood. Whole-genome sequencing can identify all noncoding variants, yet the discrimination of causal regulatory mutations represents a formidable challenge. We used epigenomic annotation in human embryonic stem cell (hESC)-derived pancreatic progenitor cells to guide the interpretation of whole-genome sequences from individuals with isolated pancreatic agenesis. This analysis uncovered six different recessive mutations in a previously uncharacterized ~400-bp sequence located 25 kb downstream of PTF1A (encoding pancreas-specific transcription factor 1a) in ten families with pancreatic agenesis. We show that this region acts as a developmental enhancer of PTF1A and that the mutations abolish enhancer activity. These mutations are the most common cause of isolated pancreatic agenesis. Integrating genome sequencing and epigenomic annotation in a disease-relevant cell type can thus uncover new noncoding elements underlying human development and disease.
AU  - Weedon,MN
AU  - Cebola,I
AU  - Patch,A-M
AU  - Flanagan,SE
AU  - De,Franco E
AU  - Caswell,R
AU  - Rodríguez-Seguí,SA
AU  - Shaw-Smith,C
AU  - Cho,CH-H
AU  - Allen,HL
AU  - Houghton,JA
AU  - Roth,CL
AU  - Chen,R
AU  - Hussain,K
AU  - Marsh,P
AU  - Vallier,L
AU  - Murray,A
AU  - International,Pancreatic Agenesis Consortium
AU  - Ellard,S
AU  - Ferrer,J
AU  - Hattersley,AT
DO  - 10.1038/ng.2826
EP  - 64
PY  - 2014///
SN  - 1061-4036
SP  - 61
TI  - Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.
T2  - Nature genetics
UR  - http://dx.doi.org/10.1038/ng.2826
UR  - http://hdl.handle.net/10044/1/71050
VL  - 46
ER  -
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