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}
}
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 -
