Huntington Hastalığı ile İlişkili ERN1 ve TRAF2 Genlerindeki Yanlış Anlamlı SNP'lerin In Silico Değerlendirilmesi

Year 2024, Volume: 11 Issue: 2, 244 - 254, 29.11.2024

Nurbanu Tanrıverdi , Ömer Faruk Karasakal , Mesut Karahan

https://doi.org/10.35193/bseufbd.1329328

Abstract

Huntington hastalığı (HD), kromozomun 4. kolundaki HTT genindeki CAG trinükleotidlerinin tekrarı sonucu beyin nöronlarında ciddi dejenerasyona neden olan ve ölümle sonuçlanabilecek bir hastalıktır. Bu çalışma, Huntington hastalığı ile ilişkili ERN1 ve TRAF2 genlerinin yanlış anlamlı SNP'lerinde potansiyel olarak zararlı etkileri olanların biyoinformatik yazılım araçları kullanılarak belirlenmesini ve bunların proteinlerin fonksiyonları ve stabilizasyonu üzerindeki etkilerinin değerlendirilmesini amaçlamıştır. Yanlış anlamlı SNP'lerin potansiyel olarak zararlı etkilerini tahmin etmek için SNAP2, SIFT, PolyPhen-2 (HumDiv ve HumVar), SNPs&GO, PhD-SNP, PANTHER ve Meta-SNP, protein stabilizasyonu için I-Mutant 2.0 ve MUpro, üç boyutlu modelleme için Project HOPE, gen-gen etkileşimleri için GeneMANIA ve protein-protein etkileşimlerinin belirlenmesi için STRING yazılım araçları kullanıldı. Huntington hastalığı ile ilişkili ERN1 ve TRAF2 genleri için 7 farklı programda 8 yazılım aracı kullanılarak 7’si ve üzerinde ortak zararlı etkiye sahip olan varyantlar seçildi. Sonuç olarak hastalıkla ilişkili olduğu düşünülen ERN1 ve TRAF2 genleri için toplam 4 varyant belirlendi. ERN1 geni için rs138082110 (S224C), rs199512451 (G133R), rs370210153 (P623Q) varyantlarının, TRAF2 geni için ise rs144405558 (C469R) varyantının olası zararlı etkiye sahip olabileceği çalışma sonucunda belirlenmiştir. Bu çalışmalar sonucunda elde edilen veriler Huntington hastalığı ile ilgili yapılacak ileri araştırmalarda ve deneysel çalışmalarda fayda sağlayacaktır.

Keywords

Huntington Hastalığı, ERN1, TRAF2, Biyoinformatik Analiz

In Silico Evaluation of Missense SNPs in ERN1 and TRAF2 Genes Associated with Huntington's Disease

Abstract

Huntington's disease (HD) is a disease that results from the repetition of CAG trinucleotides in the HTT gene in the 4th arm of the chromosome, causing severe degeneration of brain neurons and may result in death. This study aimed to identify those with potentially harmful effects in the missense SNPs of ERN1 and TRAF2 genes associated with Huntington's disease, using bioinformatics software tools, and to evaluate their impact on the functions and stabilization of proteins. SNAP2, SIFT, PolyPhen-2 (HumDiv and HumVar), SNPs&GO, PhD-SNP, PANTHER and Meta-SNP to predict potentially deleterious effects from missense SNPs, I- Mutant 2.0 and MUpro for protein stabilization, Project HOPE for three-dimensional modeling, GeneMANIA for gene-gene interactions and STRING software tools for determination of protein-protein interactions were used. For ERN1 and TRAF2 genes associated with Huntington's disease, variants with 7 or more common deleterious effects were selected using 8 software tools in 7 different programs. As a result, a total of 4 variants were identified for the ERN1 and TRAF2 genes, which were thought to be associated with the disease. As a result of the study, it was determined that the rs138082110 (S224C), rs199512451 (G133R), rs370210153 (P623Q) variants for the ERN1 gene and the rs144405558 (C469R) variant for the TRAF2 gene may have potentially harmful effects. The data obtained as a result of these studies will be beneficial in further research and experimental studies on Huntington's disease.

Keywords

Huntington, ERN1, TRAF2, Bioinformatics Analysis

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