title: Abberent expression analysis of LMNA gene in hutchinson-gilford progeria syndrome.
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 Å 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.
authors.affiliation: Department of Bioinformatics, Mohammad Ali Jinnah University, Islamabad, Pakistan.
authors.forename: Afifa
authors.initials: A
authors.lastname: Navid
authors.forename: Mohammad Haroon
authors.initials: MH
authors.lastname: Khan
authors.forename: Hamid
authors.initials: H
authors.lastname: Rashid