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Title

Abberent expression analysis of LMNA gene in hutchinson-gilford progeria syndrome

 

Authors

Afifa Navid, Mohammad Haroon Khan, Hamid Rashid*

 

Affiliation

Department of Bioinformatics, Mohammad Ali Jinnah University, Islamabad, Pakistan.

 

Email

drhamid@jinnah.edu.pk; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received February 22, 2012; Accepted March 03, 2012; Published March 17, 2012

 

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is caused by de novo dominant point mutations of the genes encoding nuclear lamina proteins, leading towards premature aging. A protein sequence is subjected to mutations in nature which can affect the function and folding pattern of the protein by different ways. Mutations involved in HGPS were identified and were substituted in the seed sequence retrieved from the UniProt database to get the mutated versions. Tertiary structure of the Lamin A protein was previously unpredicted so was performed for all the mutated as well as for the seed protein to analyze the effects of mutations on the protein structure, folding and interactions. All the predicted models were refined and validated through multiple servers for multiple parameters. The validated 3D structure of seed protein was then successfully submitted to the Protein Model Database and was assigned with the PMDB ID PM0077829. All the predicted structures were superimposed with a root mean square deviation value of 7.0 and a high Dali Z-score of 1.9. It was observed that mutations affected physiochemical properties as well as instability index and thus is affecting the domains in specific and the whole structure in general. It was further analyzed that HGPS is the result of affected Lamin a protein interactions with other integral and binding proteins in the inner nuclear membrane affecting the link in between the nuclear membrane and the network of the lamina.

 

Keywords

LMNA Gene, Lamin a protein, Mutations, Tertiary structure, Domain

 

Citation

Navid et al. Bioinformation 8(5): 221-224 (2012)
 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.