2019

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Browsing 2019 by Author "SOBIA NAZIR CHAUDRY"

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    In silico analysis for pathogenic variants in ap4 complex associated with hereditary spastic paraplegia
    (UMT, Lhr, 2019) SOBIA NAZIR CHAUDRY
    Hereditary spastic paraplegia (HSP) is characterized as neurological, heterogenous group of disease and known to be a genetic disease. Patients suffering from this disorder cannot work properly, show spasticity in lower limbs along with other neurological symptoms. Comprehensive HSP genes study reported 72 different HSP gait disease loci along with 55 spastic paraplegia cloned genes. In order to characterize a fine strategy towards functional research, we have selected missense, splicing, frameshift, stop gained and regulatory variants in SPG47, SPG50, SPG51 genes part of AP-4 complex, studied through bioinformatic tools. These bioinformatic tools predict effect of deleterious mutations not only at protein level but also at RNA level through computational modelling. In our current study we have used PHD-SNPg, PredictSNP2, PROVEAN, SNAP2, SNP&GO, MutPred tools to study amino acid substitution, then to study effect of mutation on protein stability i-Mutant was used. Splicing variants were analyzed using splice man, spice, and HSF. Regulatory variants were analyzed using ABC4DE tool. Results obtained from these tools were compared with functional data. In silico analysis highlights which variants are worth studying through functional approaches. Predicted mutations rapidly provide prognosis value to genotyping results, would be available for research purposes and patient care. Our In silico studies pays attention to opt functional approach for identified deleterious mutations. Special concern should be payed towards single nucleotide polymorphism that occurs in coding and non-coding regions causing alteration in RNA, should be verified through functional studies.