Meme kanseri ile ilişkili DVL3 ve LRP5genlerindeki SNP'lerin in siliko araçlar kullanılarak değerlendirilmesi
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Dosyalar
Tarih
2024
Yazarlar
Dergi Başlığı
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Cilt Başlığı
Yayıncı
Selçuk Üniversitesi, Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
İnsan genomundaki tek baz çift değişikliği sonucunda tek nükleotid polimorfizmleri (SNP) oluşur. Mutasyon türleri arasında bulunan en yaygın varyasyonlardır. Kalıtsal genetik bozukluklar ve insan hastalıkları SNP'lerle ilişkilidir. İlişkili olduğu hastalıklardan biri de meme kanseridir. Meme kanserinin başlaması ve ilerlemesinde çevresel, metabolik, genetik gibi faktörler etkili olabilir. Bu nedenle meme kanserini etkileyen genetik faktörlerin daha iyi anlaşılmasını sağlamak için hastalığa sebep olan genlerin ve polimorfizmlerinin araştırılması gerekmektedir. DVL3 geni meme kanseri hücrelerinin büyümesini ve çoğalmasını etkileyerek kanserin gelişimini kontrol eder. LRP5 geni ise meme kanserinin erken teşhisinde ve tedavisinde kullanılmaktadır. Kanser hücresinin büyümesinde etkili olan proteinlerin üretilmesinde rol oynar. Bu çalışmada DVL3 ve LRP5 genlerinin meme kanserinde potansiyel bir biyobelirteç olarak belirlenebilmesi için UALCAN aracı ile sağkalım analizleri gerçekleştirilmiştir. Genlere ait SNP'ler in siliko araçlar kullanarak analiz edilmiştir. Çeşitli araçlar kullanılarak SNP'lerin tahminlerinin gerçekleştirilmesi, zararlı SNP'lerin tanımlanması, proteinler üzerindeki etkileri, gen ve proteinlerle olan etkileşimleri, proteinlerin üç boyutlu modellemelerinin yapılması amaçlanmıştır. Genlere ve SNP'lere ait veriler NCBI, NCBI dbSNP, KEGG, cBioPortal, UniProt veri tabanları kullanılarak ve analiz edilerek elde edilmiştir. Zararlı yanlış anlamlı SNP'lerin belirlenmesi için SIFT, Poylphen-2, SNAP2, SNPs&GO, PANTHER, ALING GVGD ve PHD-SNP araçları kullanılmıştır. Zararlı olarak tahmin edilen SNP'lerin protein stabilizasyonu üzerindeki etkilerinin analizi için I-Mutant 2.0 ve MUpro araçları, proteinlerin modellemeleri için HOPE, gen-gen etkileşimi için GeneMANIA, protein-protein etkileşimleri için STRING aracı kullanılmıştır. Bu yazılım araçlarıyla yapılan analizler sonucunda DVL3 genine ait 6 yanlış anlamlı SNP (rs752732066 (L506P) rs768658829 (G561D), rs771458852 (R429C), rs1187186969 (R461W), rs1208232744 (L21P), rs1418995595 (E427G)) zararlı olarak bulunmuştur. LRP5 genine ait 22 yanlış anlamlı SNP (rs80358308 (R444C), rs80358313 (G610R), rs113804402 (Y1082C), rs121908665 (R570W), rs121908669 (G171R), rs121908674 (R752G), rs183377804 (R178L), rs200484935 (R186W), rs200728516 (R178W), rs201207267 (P670L), rs201916993 (R746W), rs371690402 (R44W), rs373823574 (R175G), rs377144001 (W560C), rs80358311 (G550R), rs139896674 (C336Y), rs200740071 (R349W), rs201093134 (R142W), rs201957991 (R1095C), rs368250404 (R131C), rs371514699 (R353W), rs376089595 (L150R)) zararlı olarak tespit edilmiştir. Biyoinformatik araçlar ile yapılan bu analizin, meme kanseriyle ilişkili olan DVL3 ve LRP5 genlerine dair yapılacak olan deneysel çalışmalara yol göstereceği düşünülmektedir
As a result of a single base double change in the human genome, single nucleotide polymorphisms (SNPs) are formed. They are the most common variations found between types of mutations. Hereditary genetic disorders and human diseases are associated with SNPs. One of the diseases it is associated with is breast cancer. Factors such as environmental, metabolic and genetic may be effective in the initiation and progression of breast cancer. For this reason, it is necessary to investigate the genes and polymorphisms that cause the disease in order to provide a better understanding of the genetic factors affecting breast cancer. The DVL3 gene controls the development of cancer by affecting the growth and proliferation of breast cancer cells. The LRP5 gene is used for early detection and treatment of breast cancer. It plays a role in the production of proteins that are effective in the growth of the cancer cell. In this study, survival analyzes were performed with the UALCAN tool to identify DVL3 and LRP5 genes as a potential biomarker in breast cancer. SNPs of genes were analyzed using in silico tools. It is aimed to realize the predictions of SNP's using various tools, to identify harmful SNP's, their effects on proteins, their interactions with genes and proteins, to make three-dimensional modeling of proteins. Data on genes and SNPs were obtained by using and analyzing NCBI, NCBI dbSNP, KEGG, cBioPortal, UniProt databases. SIFT, Poylphen-2, SNAP2, SNPs&GO, PANTHER, ALING GVGD and PHD-SNP tools were used to identify harmful misaligned SNPs. For the analysis of the effects of harmfully predicted SNPs on protein stabilization, I-Mutant 2.0 and MUpro tools, HOPE for modeling proteins, GeneMANIA for gene-gen interaction, STRING for protein-protein interactions were used. As a result of the analyzes performed with these software tools, 6 missense SNPs belonging to the DVL3 gene (rs752732066(L506P), rs768658829 (G561D), rs771458852(R429C), rs1187186969(R461W), rs1208232744(L21P), rs1418995595). (E427G)) was found to be harmful. 22 missense SNPs of the LRP5 gene (rs80358308(R444C), rs80358313(G610R), rs113804402(Y1082C), rs121908665(R570W), rs121908669(G171R), rs121908674(R752G), rs183377804 (R178L), rs200484935(R186W), rs200728516(R178W), rs201207267(P670L), rs201916993(R746W), rs371690402(R44W), rs373823574 (R175G), rs377144001 (W560C), rs80358311 (G550R), rs139896674(C336Y), rs200740071(R349W), rs201093134(R142W), rs201957991(R1095C), rs368250404(R131C), rs371514699(R353W), rs376089595(L150R)) have been identified as harmful.This analysis with bioinformatics will lead to experimental studies of the DVL3 and LRP5 genes associated with breast cancer.
As a result of a single base double change in the human genome, single nucleotide polymorphisms (SNPs) are formed. They are the most common variations found between types of mutations. Hereditary genetic disorders and human diseases are associated with SNPs. One of the diseases it is associated with is breast cancer. Factors such as environmental, metabolic and genetic may be effective in the initiation and progression of breast cancer. For this reason, it is necessary to investigate the genes and polymorphisms that cause the disease in order to provide a better understanding of the genetic factors affecting breast cancer. The DVL3 gene controls the development of cancer by affecting the growth and proliferation of breast cancer cells. The LRP5 gene is used for early detection and treatment of breast cancer. It plays a role in the production of proteins that are effective in the growth of the cancer cell. In this study, survival analyzes were performed with the UALCAN tool to identify DVL3 and LRP5 genes as a potential biomarker in breast cancer. SNPs of genes were analyzed using in silico tools. It is aimed to realize the predictions of SNP's using various tools, to identify harmful SNP's, their effects on proteins, their interactions with genes and proteins, to make three-dimensional modeling of proteins. Data on genes and SNPs were obtained by using and analyzing NCBI, NCBI dbSNP, KEGG, cBioPortal, UniProt databases. SIFT, Poylphen-2, SNAP2, SNPs&GO, PANTHER, ALING GVGD and PHD-SNP tools were used to identify harmful misaligned SNPs. For the analysis of the effects of harmfully predicted SNPs on protein stabilization, I-Mutant 2.0 and MUpro tools, HOPE for modeling proteins, GeneMANIA for gene-gen interaction, STRING for protein-protein interactions were used. As a result of the analyzes performed with these software tools, 6 missense SNPs belonging to the DVL3 gene (rs752732066(L506P), rs768658829 (G561D), rs771458852(R429C), rs1187186969(R461W), rs1208232744(L21P), rs1418995595). (E427G)) was found to be harmful. 22 missense SNPs of the LRP5 gene (rs80358308(R444C), rs80358313(G610R), rs113804402(Y1082C), rs121908665(R570W), rs121908669(G171R), rs121908674(R752G), rs183377804 (R178L), rs200484935(R186W), rs200728516(R178W), rs201207267(P670L), rs201916993(R746W), rs371690402(R44W), rs373823574 (R175G), rs377144001 (W560C), rs80358311 (G550R), rs139896674(C336Y), rs200740071(R349W), rs201093134(R142W), rs201957991(R1095C), rs368250404(R131C), rs371514699(R353W), rs376089595(L150R)) have been identified as harmful.This analysis with bioinformatics will lead to experimental studies of the DVL3 and LRP5 genes associated with breast cancer.
Açıklama
Anahtar Kelimeler
DVL3, İn Siliko, LRP5, Meme Kanseri, SNP, In Silico, Breast Cancer
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Doğan F., (2024). Meme Kanseri ile İlişkili DVL3 ve LRP5Genlerindeki SNP'lerin in Siliko Araçlar Kullanılarak Değerlendirilmesi . (Yüksek Lisans Tezi). Selçuk Üniversitesi, Fen Bilimleri Enstitüsü, Konya.
