Analysis of wide and variants obtained by new generationlayout method in individuals with mefv gene mutations:Retrospective work

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Thesis Type: Postgraduate

Institution Of The Thesis: Bursa Uludağ University, Turkey

Approval Date: 2019

Thesis Language: Turkish

Student: Zeynep Kurt

Co-Supervisor: ŞEBNEM ÖZEMRİ SAĞ, ELİF UZ YILDIRIM

Abstract:

The MEFV gene is located on the short arm of chromosome 16 spanning a region of 115 kb in human. This gene encodes a transcript of approximately 3.7 kb. The product of this gene encodes 781 amino acid pyrin protein. Pyrin is expressed only in mature granulocytes. The major function of pyrin is to reduce neutrophil activation and suppress inflammation. B30.2, one of the four domains of pyrin; interacts with caspase- 1. It reduces activation of caspase-1 and production of IL-1b. Excessive production of IL-1b in response to ordinary stimuli has been recorded on pyrin mutations. Interleukin IL –2, IL-6, IL-8 and Tumor Necrosis Factor-alpha (TNF-α) levels were found to be high during the attack period. FMF (Familial Mediterranean Fever) is one of the most common auto-inflammatory diseases caused by mutations in the MEFV gene. The disease is characterized by sudden onset of fever and inflammation of serous membranes. FMF is widespread in the Mediterranean region and common especially among Sephardic Jews, Armenians, Arabs and Turks. The aim of this study was to identify and classify MEVF gene variants in Turkish FMF patients using in silico tools. Novel variants are also determined and classified in this context. Sequencing of the gene is performed using Next Generation Sequencing. DNA was obtained from peripheral blood samples obtained from 1514 patients (673 males and 841 females). Initial data were analyzed with Sophia DDM program. As a result, 104 variants were detected. 75 of them were located in exons and 29 in introns. Of these variants, 13 were novel (7 exonic and 6 intronic). These variants were then subjected to various classifications according to their pathogenicity using various in silico analyzes. In addition, the amino acid changes have been analyzed using web tools to determine whether these changes have a role in post-translational modifications. Lastly, allele frequencies of the variants were calculated and compared to the previous data in the literature.