Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP)
Introduction: Familial adenomatous polyposis (FAP) is a rare and hereditary disease in which multiple precancerous polyps develop in the patient's colon. Familial adenomatous polyposis is caused by mutations in the APC gene (5q21). According to new research, in addition to nuclear disorders, mi...
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Shahid Sadoughi University of Medical Sciences
2023-08-01
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| Series: | Majallah-i Dānishgāh-i ’Ulūm-i Pizishkī-i Shahīd Ṣadūqī Yazd |
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| Online Access: | http://jssu.ssu.ac.ir/article-1-5909-en.pdf |
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| author | Mohammad Mehdi Heidari Fatemeh Ebrahimi Zahra Shaker Ardakani Mahsa Mirzaei Shima Mirhosseini Mehri Khatami |
| author_facet | Mohammad Mehdi Heidari Fatemeh Ebrahimi Zahra Shaker Ardakani Mahsa Mirzaei Shima Mirhosseini Mehri Khatami |
| author_sort | Mohammad Mehdi Heidari |
| collection | DOAJ |
| description | Introduction: Familial adenomatous polyposis (FAP) is a rare and hereditary disease in which multiple precancerous polyps develop in the patient's colon. Familial adenomatous polyposis is caused by mutations in the APC gene (5q21). According to new research, in addition to nuclear disorders, mitochondrial functional disorders are also one of the essential carcinogenic factors and also a promising target for cancer treatment. The aim of this study was to investigate the nucleotide changes of mitochondrial ATPase6 and MT-CYB genes in patients with FAP.
Methods: In this study, 9 Iranian families with Familial adenomatous polyposis were investigated to study mutations in mitochondrial genes. For this purpose, a fragment with the length of 558bp containing the ATPase6 gene and also a fragment containing the MT-CYB gene with a length of 853bp were studied using the Touchdown-PCR method and sequencing. Sequencing results were analyzed with several bioinformatics software and databases, including ExPASy, SIFT, PSIPRED, PolyPhen-2, I-Mutant, PROVEAN, PredictSNP, and PyMol.
Results: In this research, five mutations were observed in the mitochondrial ATPase6 gene. Three mutations were synonymous (c.A8901G; p.L125L, c.C8958T; p.I144I and c.C8943T; p.P139P) and two non-synonymous mutations (c.T8780C; p.L85P and c.G9133A; p.E203K). Furthermore, two synonymous mutations (c.A15607G; p.K287K and c.C15833T; p.L363L) and one non-synonymous mutation (c.C15452A; p.L236I) were observed in the MT-CYB gene.
Conclusion: In this study, ATPase6 and MT-CYB genes were investigated in the patients with Familial adenomatous polyposis, and 5 and 3 mutations and nucleotide changes were observed in affected patients, respectively. Considering that mitochondrial genome mutations can play a role in tumorigenesis, identifying new mutations can be effective in early cancer diagnosis. More studies are needed to confirm the association between mitochondrial mutations and FAP disease. |
| first_indexed | 2024-03-12T16:58:03Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2228-5741 2228-5733 |
| language | fas |
| last_indexed | 2024-03-12T16:58:03Z |
| publishDate | 2023-08-01 |
| publisher | Shahid Sadoughi University of Medical Sciences |
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| series | Majallah-i Dānishgāh-i ’Ulūm-i Pizishkī-i Shahīd Ṣadūqī Yazd |
| spelling | doaj.art-b7f06f46ba024ecd85c2cb1b104cc5072023-08-08T02:54:15ZfasShahid Sadoughi University of Medical SciencesMajallah-i Dānishgāh-i ’Ulūm-i Pizishkī-i Shahīd Ṣadūqī Yazd2228-57412228-57332023-08-0131566326645Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP)Mohammad Mehdi Heidari0Fatemeh Ebrahimi1Zahra Shaker Ardakani2Mahsa Mirzaei3Shima Mirhosseini4Mehri Khatami5 Department of Biology, Yazd University, Yazd, Iran. Department of Biology, Yazd University, Yazd, Iran. Department of Biology, Yazd University, Yazd, Iran. Department of Biology, Yazd University, Yazd, Iran. Department of Biology, Yazd University, Yazd, Iran. Department of Biology, Yazd University, Yazd, Iran. Introduction: Familial adenomatous polyposis (FAP) is a rare and hereditary disease in which multiple precancerous polyps develop in the patient's colon. Familial adenomatous polyposis is caused by mutations in the APC gene (5q21). According to new research, in addition to nuclear disorders, mitochondrial functional disorders are also one of the essential carcinogenic factors and also a promising target for cancer treatment. The aim of this study was to investigate the nucleotide changes of mitochondrial ATPase6 and MT-CYB genes in patients with FAP. Methods: In this study, 9 Iranian families with Familial adenomatous polyposis were investigated to study mutations in mitochondrial genes. For this purpose, a fragment with the length of 558bp containing the ATPase6 gene and also a fragment containing the MT-CYB gene with a length of 853bp were studied using the Touchdown-PCR method and sequencing. Sequencing results were analyzed with several bioinformatics software and databases, including ExPASy, SIFT, PSIPRED, PolyPhen-2, I-Mutant, PROVEAN, PredictSNP, and PyMol. Results: In this research, five mutations were observed in the mitochondrial ATPase6 gene. Three mutations were synonymous (c.A8901G; p.L125L, c.C8958T; p.I144I and c.C8943T; p.P139P) and two non-synonymous mutations (c.T8780C; p.L85P and c.G9133A; p.E203K). Furthermore, two synonymous mutations (c.A15607G; p.K287K and c.C15833T; p.L363L) and one non-synonymous mutation (c.C15452A; p.L236I) were observed in the MT-CYB gene. Conclusion: In this study, ATPase6 and MT-CYB genes were investigated in the patients with Familial adenomatous polyposis, and 5 and 3 mutations and nucleotide changes were observed in affected patients, respectively. Considering that mitochondrial genome mutations can play a role in tumorigenesis, identifying new mutations can be effective in early cancer diagnosis. More studies are needed to confirm the association between mitochondrial mutations and FAP disease.http://jssu.ssu.ac.ir/article-1-5909-en.pdfnucleotide variationsfamilial adenomatous polyposismitochondriaatpase6mt-cyb. |
| spellingShingle | Mohammad Mehdi Heidari Fatemeh Ebrahimi Zahra Shaker Ardakani Mahsa Mirzaei Shima Mirhosseini Mehri Khatami Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP) Majallah-i Dānishgāh-i ’Ulūm-i Pizishkī-i Shahīd Ṣadūqī Yazd nucleotide variations familial adenomatous polyposis mitochondria atpase6 mt-cyb. |
| title | Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP) |
| title_full | Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP) |
| title_fullStr | Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP) |
| title_full_unstemmed | Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP) |
| title_short | Molecular Study of Nucleotide Changes of ATPase6 and MT-CYB Genes in the Mitochondrial Genome of Patients with Familial Adenomatous Polyposis (FAP) |
| title_sort | molecular study of nucleotide changes of atpase6 and mt cyb genes in the mitochondrial genome of patients with familial adenomatous polyposis fap |
| topic | nucleotide variations familial adenomatous polyposis mitochondria atpase6 mt-cyb. |
| url | http://jssu.ssu.ac.ir/article-1-5909-en.pdf |
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