Imperial College London
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DrCarolynMillar

Faculty of Medicine, Department of Immunology and Inflammation

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 2153c.millar

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Westbury:2015:10.1186/s13073-015-0151-5,
author = {Westbury, SK and Turro, E and Greene, D and Lentaigne, C and Kelly, AM and Bariana, TK and Simeoni, I and Pillois, X and Attwood, A and Austin, S and Jansen, SBG and Bakchoul, T and Crisp-Hihn, A and Erber, WN and Favier, R and Foad, N and Gattens, M and Jolley, JD and Liesner, R and Meacham, S and Millar, CM and Nurden, AT and Peerlinck, K and Perry, DJ and Poudel, P and Schulman, S and Schulze, H and Stephens, JC and Furie, B and Robinson, PN and van, Geet C and Rendon, A and Gomez, K and Laffan, MA and Lambert, MP and Nurden, P and Ouwehand, WH and Richardson, S and Mumford, AD and Freson, K},
doi = {10.1186/s13073-015-0151-5},
journal = {Genome Medicine},
title = {Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders},
url = {http://dx.doi.org/10.1186/s13073-015-0151-5},
volume = {7},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundHeritable bleeding and platelet disorders (BPD) are heterogeneous and frequently have an unknown genetic basis. The BRIDGE-BPD study aims to discover new causal genes for BPD by high throughput sequencing using cluster analyses based on improved and standardised deep, multi-system phenotyping of cases.MethodsWe report a new approach in which the clinical and laboratory characteristics of BPD cases are annotated with adapted Human Phenotype Ontology (HPO) terms. Cluster analyses are then used to characterise groups of cases with similar HPO terms and variants in the same genes.ResultsWe show that 60% of index cases with heritable BPD enrolled at 10 European or US centres were annotated with HPO terms indicating abnormalities in organ systems other than blood or blood-forming tissues, particularly the nervous system. Cases within pedigrees clustered closely together on the bases of their HPO-coded phenotypes, as did cases sharing several clinically suspected syndromic disorders. Cases subsequently found to harbour variants in ACTN1 also clustered closely, even though diagnosis of this recently described disorder was not possible using only the clinical and laboratory data available to the enrolling clinician.ConclusionsThese findings validate our novel HPO-based phenotype clustering methodology for known BPD, thus providing a new discovery tool for BPD of unknown genetic basis. This approach will also be relevant for other rare diseases with significant genetic heterogeneity.
AU  - Westbury,SK
AU  - Turro,E
AU  - Greene,D
AU  - Lentaigne,C
AU  - Kelly,AM
AU  - Bariana,TK
AU  - Simeoni,I
AU  - Pillois,X
AU  - Attwood,A
AU  - Austin,S
AU  - Jansen,SBG
AU  - Bakchoul,T
AU  - Crisp-Hihn,A
AU  - Erber,WN
AU  - Favier,R
AU  - Foad,N
AU  - Gattens,M
AU  - Jolley,JD
AU  - Liesner,R
AU  - Meacham,S
AU  - Millar,CM
AU  - Nurden,AT
AU  - Peerlinck,K
AU  - Perry,DJ
AU  - Poudel,P
AU  - Schulman,S
AU  - Schulze,H
AU  - Stephens,JC
AU  - Furie,B
AU  - Robinson,PN
AU  - van,Geet C
AU  - Rendon,A
AU  - Gomez,K
AU  - Laffan,MA
AU  - Lambert,MP
AU  - Nurden,P
AU  - Ouwehand,WH
AU  - Richardson,S
AU  - Mumford,AD
AU  - Freson,K
DO  - 10.1186/s13073-015-0151-5
PY  - 2015///
SN  - 1756-994X
TI  - Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders
T2  - Genome Medicine
UR  - http://dx.doi.org/10.1186/s13073-015-0151-5
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000354082200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/33110
VL  - 7
ER  -
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