Alzheimer Hastalığıyla İlişkili BID, MAPK10 ve AGER Genlerindeki SNP ve miRNA'ların In Silico Araçlar Kullanılarak Değerlendirilmesi

Alzheimer hastalığı (AH), beyinde hücre içi hiperfosforile tau proteini, nörofibril yumakları ve hücre dışı amiloid β proteininin birikimi ile patolojik olarak tanımlanan hem genetik hem de çevresel faktörlerden kaynaklanan multifaktöriyel bir hastalıktır. Bu çalışmanın amacı, çeşitli in silico araçları kullanarak AH ile ilişkili BID, MAPK10 ve AGER genlerindeki yanlış anlamlı tek nükleotid polimorfizmlerinin (SNP'ler) potansiyel olarak zarar verici etkilerini tahmin etmek ve SNP'lerin miRNA'lar üzerindeki etkilerini belirlemektir. Ayrıca çeşitli yazılım araçları ile gen-gen ve protein-protein etkileşimlerinin belirlenmesi amaçlanmaktadır. Sonuç olarak, BID geninde yedi, MAPK10 geninde yirmi yedi ve AGER geninde üç polimorfizmin zararlı etkilerinin olabileceği tahmin edilmiştir. BID ve MAPK10 genlerinde bazı SNP'lerin miRNA-mRNA bağlanmasının etkinliğini azalttığı, arttırdığı, kırdığı, yeni bir bağlanma bölgesi oluşturduğu ve/veya miRNA-mRNA bağlama bölgesini yok ettiği elde edilmiştir. miRNA-SNP analizlerinde AGER genine ait bilgi edinilememiştir. Bu çalışmada BID, MAPK10 ve AGER genlerindeki yüksek riskli olduğu tahmin edilen SNP'ler gelecekteki genotipleme çalışmaları için veri sağlayabilecektir. Yüksek riskli olduğu tahmin edilen SNP'ler ve miRNA-mRNA aktivitesinde rolü olabilecek SNP'ler AH ile ilgili deneysel çalışmalarda öncelikli olarak değerlendirilebilecektir. Gelecekte, zararlı/hastalıkla ilgili yanlış anlamlı SNP'lerin ve mRNA-miRNA etkileşimini etkileyen SNP'lerin klinik etkilerini araştırmak için deneysel çalışmalar önerilmektedir.

Anahtar Kelimeler:

Alzheimer Hastalığı, AGER, BID, MAPK10, In silico

Evaluation of SNPs and miRNAs in the BID, MAPK10, and AGER Genes Related to Alzheimer's Disease by Using In Silico Tools

Alzheimer's disease (AD) is a multifactorial disease resulting from both genetic and environmental factors, which are pathologically defined by the accumulation of intracellular hyperphosphorylated tau protein, neurofibrils tangles, and extracellular amyloid β protein in the brain. The purpose of this study is to estimate the potentially damaging effects of missense single nucleotide polymorphisms (SNPs) in the BID, MAPK10 and AGER genes associated with AD using various in silico tools and to determine the effects of SNPs on miRNAs. In addition, it is aimed to determine the gene-gene and protein-protein interactions through various software tools. Consequently, it was estimated that there may be harmful effects of seven polymorphisms in the BID gene, twenty-seven in the MAPK10 gene and three in the AGER gene. It was obtained that some SNPs decrease the effectiveness of miRNA-mRNA binding, enhance, break, create a new binding zone and/or destroy the miRNA-mRNA binding zone in the BID and MAPK10 genes. miRNA-SNP analyses could not provide information on the AGER gene. In this study, SNPs in the BID, MAPK10, and AGER genes, which are estimated to be high-risk SNPs, will be able to provide data for future genotyping studies. SNPs that are estimated to be high-risk and SNPs that may have a role in miRNA- mRNA activity can be assessed as a priority in experimental studies related to AD. In the future, experimental studies are proposed to investigate the clinical effects of harmful/disease-related missense SNPs and SNPs affecting mRNA-miRNA interaction.

Keywords:

Alzheimer’s Disease, AGER, BID, MAPK10, In silico,

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