Klinik Ekzom Sekans Trio Örneklerinde De Novo Mutasyonların Sıklığı ve Karakteristik Özlelliklerinin Araştırılması

Year 2024, , 266 - 272, 30.04.2024

Nadir Koçak , Ali Torabi , Batuhan Şanlıtürk , Ozkan Bagci , Ebru Marzioğlu-özdemir , Tülin Çora

https://doi.org/10.54005/geneltip.1463733

Abstract

Gelişmiş genom dizileme teknolojileri, genom ile ilişkilendirilen koşulların mekanizmalarını derinlemesine anlama fırsatı sunmuştur. Son zamanlarda, üreme hücrelerinde ortaya çıkan ve ebeveynlerde bulunmayan genetik değişiklikler olan de novo mutasyonların özelliklerini anlama konusunda önemli bir ilgi olmuştur ve oluşumlarına dahil olan mekanizmaları anlamak. Bu mutasyonlar sonraki nesillere aktarılabilir ve genetik çeşitliliği ve hastalıklara duyarlılığı etkileme potansiyeline sahiptir, bu nedenle bu konu önemlidir. Bu alandaki sınırlı çalışmalar nedeniyle, bu mutasyonların oluşum mekanizmaları ve karakteristik özellikleri henüz tam olarak anlaşılamamıştır.
Arka Plan/Hedefler: Bu çalışmada, üçlü klinik ekzom dizileme analizi geçiren ailelerde de novo mutasyonların kapsamlı bir analizini yapmayı amaçladık. Çalışmanın amaçları, ebeveyn yaşları ile de novo mutasyonların sıklığı arasındaki ilişkiyi, de novo mutasyonların dağılımını, yaygınlığını, ilişkilerini ve moleküler özelliklerini araştırmaktı.
Yöntemler: Selçuk Üniversitesi Tıp Fakültesi Tıbbi Genetik Anabilim Dalı'nda 1 Ocak 2017 ile 31 Aralık 2023 tarihleri arasında üçlü Klinik Ekzom Dizileme (CED) analizi geçiren toplam 69 aile çalışmaya dahil edildi. Bireylerin periferik venöz kanından elde edilen DNA örnekleri Roche CED kiti ve DNBSEQ-G400™ dizileme cihazı kullanılarak dizilendi ve Seq Platformu kullanılarak toplam 3892 gen analiz edildi.
Sonuçlar: Analizlerden sonra, çoğunluğu anlamsız varyantlar olan 407 de novo varyant belirlendi (%55.28). Baz değişim profilini incelediğimizde, en yaygın değişikliklerin C -> G, G -> A, A -> G olduğu bulundu. En sık mutasyona uğrayan genlerin DSPP, HPS4, VCL ve BMP4 genleri olduğu belirlendi.
Tartışma: Korelasyon analizi, ebeveyn yaşları ile de novo mutasyon sayısı arasında anlamlı bir ilişki bulunmadığını ortaya çıkardı ve regresyon analizi, yaşın de novo mutasyon sayısını belirlemede anlamlı bir parametre olmadığını gösterdi.

Keywords

Mutasyon, Ekzom sekans, Genom, Gen

Investigation of the Frequency and Characteristic Features of De Novo Mutations in Clinical Exome Sequence Trio Samples

Abstract

Advanced genome sequencing technologies have provided us with the opportunity to deeply understand the mechanisms underlying conditions associated with the genome. There has been significant interest recently in understanding the characteristics of de novo mutations, which are genetic changes that arise in reproductive cells and are not present in parents, as well as the mechanisms involved in their occurrence. These mutations can be transmitted to subsequent generations and have the potential to influence genetic diversity and susceptibility to diseases, making this topic important. Due to limited studies in this area, the formation mechanisms and characteristic features of such mutations have not yet been fully understood.
Background/Aims: In this study, we aimed to conduct a comprehensive analysis of de novo mutations in families undergoing trio clinical exome sequencing analysis. The objectives of the study were to investigate the relationship between parental ages and the frequency of de novo mutations, the distribution, prevalence, relationships, and molecular characteristics of de novo mutations.
Methods: A total of 69 families who underwent Trio Clinical Exome Sequencing (CES) analysis at the Department of Medical Genetics, Faculty of Medicine, Selçuk University, between January 1, 2017, and December 31, 2023, were included in the study. DNA samples extracted from peripheral venous blood of individuals were sequenced using the Roche CES kit and DNBSEQ-G400™ sequencing device, and a total of 3892 genes were analyzed using the Seq Platform.
Results: After analysis, 407 de novo variants were identified, with the majority being variants of unknown significance (55.28%). When examining the base change profile, the most common changes were found to be C -> G, G -> A, A -> G. The most commonly mutated genes were found to be DSPP, HPS4, VCL, and BMP4 genes.
Conclusions: Correlation analysis revealed no significant relationship between parental age and the number of de novo mutations, and regression analysis showed that age was not a significant parameter in determining the number of de novo mutations

Keywords

Mutation, Exome Sequencing, Genom, Gene

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