Evaluation of missense SNVs within human APOE (Apolipoprotein E) gene via bioinformatics tools

Abstract

Apolipoprotein E (APOE) is one of the main proteins responsible for cholesterol transport. It has three major isoforms, APOE2, APOE3, and APOE4. The purpose of this study is to investigate the possible effects of single nucleotide variations (SNVs) in the APOE gene, which cause amino acid substitution, on the function, structure and stabilization of the APOE protein using bioinformatics/s tools. SNVs and protein sequence information were obtained from NCBI and UniProt databases. Bioinformatical analysis was performed using a series of tools such as SIFT, PolyPhen-2, SNPs&GO, Mutation Assessor, PROVEAN, SNAP2, I-Mutant-3, MUPro, and Project HOPE. As a result, 321 missense SNVs were analyzed and rs7412 (R176C), rs769455 (R163C), rs11542029 (R50C), rs121918393 (R154S), rs121918394 (K164Q), rs200703101 (R154P), rs387906567 (R160C), rs11542040 (P102T), rs11542041 (R132S) and rs41382345 (E139V) were predicted to be deleterious/disease related after functional analysis and pathological effect analysis via all of the bioinformatics/s tools. According to the protein stabilization results, it was determined that all SNVs decreased protein stabilization with the MUPro software tool, and two SNVs (rs121918394, rs41382345) increased protein stabilization with the I-Mutant-3 software tool. The models of protein and amino acid properties were obtained via Project HOPE for all high-risk SNVs. We hope our analysis will be valuable for further proteomic, genomic, and clinical research.

Keywords

• Apolipoprotein E (APOE)
• cholesterol
• in silico
• single nucleotide variation (SNV)

Biyoinformatik araçlar aracılığıyla insan APOE (Apolipoprotein E) genindeki yanlış anlamlı SNV'lerin değerlendirilmesi

Abstract

Apolipoprotein E (APOE), kolesterol taşınmasından sorumlu ana proteinlerden biridir. APOE2, APOE3 ve APOE4 olmak üzere üç ana izoformu vardır. Bu çalışmanın amacı, APOE geninde amino asit yer değiştirmesine neden olan tek nükleotid varyantlarının (SNV'ler) APOE proteininin işlevi, yapısı ve stabilizasyonu üzerindeki olası etkilerini biyoinformatik araçlar kullanarak araştırmaktır. SNV'ler ve protein dizi bilgisi, NCBI ve UniProt veritabanlarından elde edilmiştir. Biyoinformatik analiz, SIFT, PolyPhen-2, SNPs&GO, Mutation Assessor, PROVEAN, SNAP2, I-Mutant-3, MUPro ve Project HOPE gibi bir dizi araç kullanılarak yapılmıştır. Sonuç olarak 321 yanlış anlamlı SNV analiz edilmiş ve rs7412 (R176C), rs769455 (R163C), rs11542029 (R50C), rs121918393 (R154S), rs121918394 (K164Q), rs200703101 (R154P), rs387906567 (R160C), 102rsT11542040 rs11542041 (R132S) ve rs41382345 (E139V)'nin tüm biyoinformatik araçları aracılığıyla fonksiyonel analiz ve patolojik etki analizinden sonra zararlı/hastalık ile ilgili olduğu tahmin edilmiştir. Protein stabilizasyon sonuçlarına göre, MUPro yazılım aracı ile tüm SNV'lerin protein stabilizasyonunu azalttığı ve I-Mutant-3 yazılım aracı ile iki SNV'nin (rs121918394, rs41382345) protein stabilizasyonunu arttırdığı belirlenmiştir. Protein ve amino asit özellikleri modelleri, tüm yüksek riskli SNV'ler için Project HOPE aracılığıyla elde edilmiştir. Analizimizin daha fazla proteomik, genomik ve klinik araştırmalar için değerli olacağını umuyoruz.

Keywords

• Apolipoprotein E (APOE)
• kolesterol
• in silico
• tek nükleotid varyantı (SNV)

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