Imperial College London
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DrAlessiaDavid

Faculty of Natural Sciences, Department of Life Sciences

Lecturer in Bioinformatics and Data Intensive Biology
 
 
 
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Contact

 

+44 (0)20 7594 5333alessia.david09

 
 
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Location

 

Department of BioinformaticsSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ittisoponpisan:2017:10.1002/humu.23155,
author = {Ittisoponpisan, S and Sternberg, MJE and Alhuzimi, E and David, A},
doi = {10.1002/humu.23155},
journal = {Human Mutation},
pages = {289--296},
title = {Landscape of pleiotropic proteins causing human disease: structural and system biology insights},
url = {http://dx.doi.org/10.1002/humu.23155},
volume = {38},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pleiotropyis  the  phenomenon  by  which  the  same  gene  can  result  in  multiple  phenotypes. Pleiotropic  proteins  are  emerging  as  important  contributors  to  rare  and  common  disorders. Nevertheless,  little  is  known  on  the  mechanisms  underlying  pleiotropy  and  the  characteristic  of pleiotropic proteins.We  analysed disease-causing  proteins  reported  in  UniProt  and observed  that 12%  are  pleiotropic (variants in  the  same  protein  cause  more  than  one  disease). Pleiotropic  proteins  were  enriched  indeleterious and rare variants, but not in common variants. Pleiotropic proteins were more likely to be involved in the pathogenesis of neoplasms, neurological and circulatory diseases, and congenital malformations,  whereas  non-pleiotropicproteinsin  endocrine  and  metabolic  disorders. Pleiotropic proteins  were  more  essential  and  hada  higher  number  of  interacting  partners  compared  to  non-pleiotropic proteins. Significantly more pleiotropic than non-pleiotropic proteins contained at least one  intrinsically  long  disordered  region  (p<0.001).  Deleterious variants occurring  in  structurally disordered regions were more commonly found in pleiotropic, rather than non-pleiotropic proteins. 14In conclusion, pleiotropic proteins are an important contributor to human disease. They represent a biologically   different   class   of   proteins   compared   to   non-pleiotropic   proteins anda better understanding  of their  characteristicsand  genetic  variants, cangreatly  aid  in  the  interpretation  of genetic studies and drug design.
AU  - Ittisoponpisan,S
AU  - Sternberg,MJE
AU  - Alhuzimi,E
AU  - David,A
DO  - 10.1002/humu.23155
EP  - 296
PY  - 2017///
SN  - 1098-1004
SP  - 289
TI  - Landscape of pleiotropic proteins causing human disease: structural and system biology insights
T2  - Human Mutation
UR  - http://dx.doi.org/10.1002/humu.23155
UR  - http://hdl.handle.net/10044/1/43037
VL  - 38
ER  -
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