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bioRxiv · 10.1101/818302

Extensive In Silico Analysis of ATL1 Gene: Discovered Five Mutations that may Cause Hereditary Spastic Paraplegia Type 3A

Mustafa, M. I.·Murshed, N. S.·Abdelmoneim, A. H.·Abdelmageed, M. I.·Elfadol, N. M.·Makhawi, A. M.
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Abstract

BACKGROUNDHereditary spastic paraplegia type 3A (SPG3A) is a neurodegenerative disease inherited type of Hereditary spastic paraplegia (HSP). It is the second most frequent type of HSP; which Characterized by muscle stiffness with paraplegia and early-onset of symptoms. This is the first translational bioinformatics analysis in a coding region of ATL1 gene which aims to categorize nsSNPs to be used as genomic biomarkers; also it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.\n\nMETHODSThe raw data of ATL1 gene were retrieved from dbSNP database, and then run into numerous computational analysis tools. Additionally; we submitted the common six deleterious outcomes from the previous functional analysis tools to I-mutant 3.0, and MUPro respectively, to investigate their effect on structural level. The 3D structure of ATL1 was predicted by RaptorX and modeled using UCSF Chimera to compare the differences between the native and the mutant amino acids.\n\nRESULTSFive nsSNPs out of 249 were classified as the most deleterious (rs746927118, rs979765709, rs119476049, rs864622269, rs1242753115).\n\nCONCLUSIONSIn this study the impact of nsSNPs in the ATL1 gene was investigated by various bioinformatics tools, that revealed five nsSNPs (V67F, T120I, R217Q, R495W and G504E) are deleterious SNPs, which have a functional impact on ATL1 protein; and therefore, can be used as genomic biomarkers specifically before 4 years old; also it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.

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Mustafa, M. I., Murshed, N. S., Abdelmoneim, A. H., Abdelmageed, M. I., Elfadol, N. M., Makhawi, A. M.. 2019-10-25. Extensive In Silico Analysis of ATL1 Gene: Discovered Five Mutations that may Cause Hereditary Spastic Paraplegia Type 3A. https://doi.org/10.1101/818302

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