Computational Analysis of Single Nucleotide Polymorphism (SNPs) in Human&amp;lt;i&amp;gt;SLC5A1&amp;lt;/i&amp;gt; Gene

Rashid Abualamah Albasheer Abbas,Hind Abdelaziz Elnasri,Mona Abdelrahman Mohamed Khaier,Afra Mohamed Suliman Albakry

doi:10.11648/j.ijbse.20190704.12

Computational Analysis of Single Nucleotide Polymorphism (SNPs) in Human&lt;i&gt;SLC5A1&lt;/i&gt; Gene

Rashid Abualamah Albasheer Abbas, Hind Abdelaziz Elnasri + Show 2 more

Open Access

https://doi.org/10.11648/j.ijbse.20190704.12

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Abstract

Glucose galactose malabsorption (GGM) is an autosomal recessive disease manifesting within the first weeks of life. It is characterized by a selective failure to absorb dietary glucose and galactose from the intestine leading to severe life threatening diarrhea and dehydration. Mutations in the Na+/glucose co-transporter gene (SLC5A1 gene) have been determined to be associated with congenital GGM. In this study different computational tools were used to investigate the nsSNPs (Single nucleotide polymorphisms) in the SLC5A1 gene and to determine their effects on the protein function and structure. SLC5A1 gene was investigated in NCBI database and SNPs were analyzed using seven computational software (SIFT, Polyphen-2, PROVEAN, SNPs and GO, PHD-SNPs, I-mutant and MU Pro). The protein structural analysis was done by modeling using Project Hope and Chimera after homology modeling by CPH models 3.2. In addition Gene MANIA software was used to study the association between this gene and related ones. A total of 166 nsSNPs were obtained from the SNPs database in NCBI during 2019. A total of 37 SNP were predicted to be deleterious using SIFT software, while 25 SNPs were predicted to be probably damaging by PolyPhen-2 and 30 SNPs were predicted to be deleterious by PROVEAN. The results of SIFT, PolyPhen-2, PROVEAN, SNPs&GO, PHD-SNP collectively revealed that 16 SNPs were predicted to be highly damaging.

Highlights

Glucose / galactose malabsorption (GGM) is an autosomal recessive disease manifesting within the first weeks of life andis characterized by a selective failure to absorb dietary glucose and galactose from the intestine [1]
The goal of this study was to analyze the nsSNPs in SLC5A1 gene and the effect of predicted mutations at the proteomic level
SLC5A1 gene plays a vital role in human body and it was found to be co-expressed and shared domains with 11 genes as predicted by GeneMANIA (Figure 1 and Table 1)

Summary

Introduction

Glucose / galactose malabsorption (GGM) is an autosomal recessive disease manifesting within the first weeks of life andis characterized by a selective failure to absorb dietary glucose and galactose from the intestine [1]. Patients with GGM are presented with the neonatal onset of severe lifethreatening watery diarrhea and dehydration [2]. It was first described in 1962 [3]. Mutations in the Na+/glucose co-transporter gene SLC5A1 (Solute Carrier Family 5 Member 1 (Sodium/Glucose Cotransporter) can cause structural and functional deletion in the SGLT-1 proteins glucose and galactose are not absorbed from the intestine leading to clinical manifestations [5]. A total of more than 40 SLC5A1 mutation have been identified in patients with congenital Glucose / galactose malabsorption up to date [6]

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Results