应用生物信息学与计算生物学杂志

Computational Analysis and Polymorphism study of Tumor Suppressor Candidate Gene-3 for Non Syndromic Autosomal Recessive Mental Retardation

Muhammad Naveed, Syeda Khushbakht Kazmi, Fiza Anwar, Fatima Arshad, Tehreem Zafar Dar and Muddassar Zafar

Computational Analysis and Polymorphism study of Tumor Suppressor Candidate Gene-3 for Non Syndromic Autosomal Recessive Mental Retardation

Mental Retardation (MR) is regarded as a neuronal malfunction characterized by a low Intellectual Quotient (IQ). To date, few genes (GRIK2, TUSC3, TRAPPC9, TECR, ST3GAL3, MED23, MAN1B1, NSUN1 PRSS12, CRBN, CC2D1A) for autosomal-recessive non syndromic MR (NS-ARMR) have been identified and established in various families with MR. The recently reported candidate gene “Tumor Suppressor Candidate Gene-3 (TUSC3)” was selected for computational analysis to explore its potential role in pathology as it is the only gene for MR reported in more than five different familial cases worldwide. TUSC3 gene located at chromosome 8p22 contains 11 exons and encodes a protein involved in the vertebrate plasma membrane magnesium ion transport system. Three dimensional structures of the candidate gene TUSC3 and its mutated structure with Q55X were generated. Template parameters were based on Z-score, E value, resolution and quality. Present study demonstrates the reliability of 3D model which satisfies the overall quality of the model constructed, employing both physiochemical and statistical model evaluation. Previously a homozygous 163C-T transition in exon 2 of the TUSC3 gene, resulting in a gln55-to-ter (Q55X) substitution has been reported. And here we predicted by PHD-SNP that X could be either proline (P) or Aspartic acid (D) causing deleterious effect. As mutation at 55 position was responsible for non-syndromic autosomal recessive mental retardation, so it was assumed that mutation was either by proline or aspartic acid. Further, MUPRO, PROVEAN, I-Mutant, Predict SNP, Meta SNP, Panther, SIFT, SNPs 3D confirmed that deleterious mutation was Q55P transition... .