In-silico Screening of Deleterious NF1 SNPs Associated with Neurofibromatosis Type I

Abstract

Neurofibromatosis type 1, also called von Recklinghausen disease, is one of the most common dominant inherited disorders. The signature of disease is the development of benign neurofibromas mainly Lisch nodules in the eye. Individuals with disease also have increased risk to develop malignant tumours, among which malignant peripheral nerve sheath tumours (MPNSTs) are the most severe case. The gene NF1 coding for Neurofibromatosis type 1 is located at chromosome 17qll.2 and its protein product is neurofibromin. Neurofibromin belongs to a family of proteins that serve as negative regulators of the ras oncogene. The proposed tumor suppressor function is supported by somatic second hit mutations of the NF1 gene in benign and malignant tumors observed in Neurofibromatosis type 1 patients. In this work, we implemented computational analysis to screen the most deleterious SNPs of NF1 gene that associated with disease. The deleterious genes will be screened by using SIFT, PolyPhen, I-mutant 2.0, SNPs and GO, PROVEAN and MutPred tools. The computational analyses identified SNPs L535P, Q538P and F62S as most deleterious based on sequence changes due to mutation. Our study insights more on critical SNPs specific to the disease mechanism and would facilitate to develop personalized medicine for Neurofibromatosis type 1.