Monogenic disorders and modifier genes: Is genotype predictive of phenotype?

Abstract

Although monogenic disorders are caused by mutations in one gene, phenotypic variability occurs in patients with the same genotype and disease expressivity changes. Modifier genes are one of the main factors that affect disease severity. In monogenic disorders such as spinal muscular atrophy (SMA), familial Mediterranean fever (FMF) or cystic fibrosis (CF), more than one gene that modifies the course of the disease has been detected. High throughput techniques used in the genomics field will provide functional research on modifier genes, pave the way to establish genotype-to-phenotype correlations and explain the pathophysiology of diseases. The modifier genes which are associated with the most common monogenic disorders in our population and their functions are summarized in this review. 

Keywords

• Monogenic disorders,Modifier genes,Genotype-tophenotype correlations

Tek gen hastalıkları ve modifiye edici genler: Genotip her zaman fenotipi yansıtır mı?

Abstract

Tek gen hastalıkları, bir gendeki mutasyonlar sonucu ortaya çıkmasına rağmen aynı genotipe sahip hastalar arasında fenotipik çeşitlilik gözlenmekte ve hastalıkların penetrans ile ekspressivitesi değişmektedir. Hastalık ciddiyetini değiştiren etkenler arasında ilk sırada fenotipi modifiye edici genler gelmektedir. Klasik Mendel türü kalıtım göstermesine rağmen fenotipik çeşitlilikler gözlenen spinal müsküler atrofi (SMA), ailevi Akdeniz ateşi (AAA) ve kistik fibrozis (KF) gibi tek gen hastalıklarında hastalık seyrini etkileyen birden fazla gen saptanmıştır. Genombilim alanında kullanılan yüksek çözünürlüklü teknikler sayesinde modifiye edici genler hakkında fonksiyonel araştırmalar yapılabilecek, genotip ile fenotip arasındaki ilişkinin kurulması ve hastalıkların patofizyolojisini açıklamak mümkün olabilecektir. Bu derlemede, toplumumuzda sık görülen tek gen hastalıklarında tanımlanmış olan fenotipi modifiye edici genler ve bu genlerin fonksiyonları özetlenmiştir. 

Keywords

• Tek gen hastalıkları,Modifiye edici genler,Genotip-fenotip korelasyonu

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