Evaluation of Pathogenicity Effects of Missense Nucleotide Polymorphisms (SNPs) in NKX2.1 Gene

سال انتشار: 1397
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 489

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شناسه ملی سند علمی:

CIGS15_077

تاریخ نمایه سازی: 13 بهمن 1398

چکیده مقاله:

Introduction: Congenital hypothyroidism (CH) is a most common congenital endocrine disorder, affecting 1 in 3000 to 4000 newborns. Nkx2.1 (thyroid transcription factor-1; also known as TTF-1) is an essential homeodomain-containing transcription factor for the morphogenesis and differentiation of the various tissues such as thyroid, lung and ventral forebrain. The purpose of this study is to examine the pathogenic effects of single nucleotide polymorphisms in the NKX2.1 gene based on bioinformatics analyzes to determine the rule of these mutations in the structure and function of mutated protein. Method: We identified three non-synonymous single nucleotide polymorphisms (nsSNPs) in the NKX2.1 gene: (rs137852693 , rs28936671 and rs28936672) using dbSNP and then analyzed their effect on the protein structure using PyMOL software and SIFT and PolyPhen-2 database.Results: Our data showed that non-synonymous single nucleotide polymorphisms change the interaction patterns, polar groups, and length of hydrogen bonds. rs28936671(Arg213Ser), and rs28936672 (Trp208Leu) SNPs caused to reducing the number of hydrogen bonds in the protein structure. In rs28936671(Arg213Ser) the positive-polar amino acid has becom non-polar amino acid. rs28936672 (Trp208Leu) converts the aromatic amino acid to aliphatic amino acid. rs137852693 (Glu205Gln) changes the polar positively charged into a polar uncharged and change in the length of hydrogen bond. The results of SIFT predict scores equal 0 and in polyphen-2 score are more than 0.98 for all three mentioned SNPs.Conclusions: According to bioinformatics assays all three of these SNPs can be harmful, deleterious and alter the structure of the protein. Computational biology tools have advantages and disadvantages, and their results are predictions that require confirmation.

کلیدواژه ها:

NKX2.1 ، non-synonymous single nucleotid polymorphisms ، structure prediction ، PyMOL ، SIFT

نویسندگان

Seyed Ali Madani Manshadi

Department of Biology, Faculty of science, Yazd University, Yazd, Iran.

Mohammad Mehdi Heidari,

Department of Biology, Faculty of science, Yazd University, Yazd, Iran.

Mehri Khatami

Department of Biology, Faculty of science, Yazd University, Yazd, Iran.