Pathogenic variants that alter protein code often disrupt splicing
نویسندگان
چکیده
منابع مشابه
Identification of pathogenic gene mutations in LMNA and MYBPC3 that alter RNA splicing.
Genetic variants that cause haploinsufficiency account for many autosomal dominant (AD) disorders. Gene-based diagnosis classifies variants that alter canonical splice signals as pathogenic, but due to imperfect understanding of RNA splice signals other variants that may create or eliminate splice sites are often clinically classified as variants of unknown significance (VUS). To improve recogn...
متن کاملMolecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function
Mutations that result in amino acid changes can affect both pre-mRNA splicing and protein function. Understanding the combined effect is essential for correct diagnosis and for establishing the most appropriate therapeutic strategy at the molecular level. We have identified a series of disease-causing splicing mutations in coagulation factor IX (FIX) exon 5 that are completely recovered by a mo...
متن کاملHigher-Order Code Splicing
Run-time code generation (RTCG) and just-in-time compilation (JIT) are features of modern programming systems to strike the balance between generality and eeciency. Since RTCG and JIT techniques are not portable and notoriously hard to implement, we propose code splicing as an alternative for dynamically-typed higher-order programming languages. Code splicing combines precompiled pieces of code...
متن کاملTowards a Splicing Code
A combination of experimental and bioinformatics approaches leads Burge and colleagues (Wang et al., 2004 [this issue of Cell]) to a global view of how an RNA segment may be selected or avoided in mature mRNAs due to biased distributions of exonic enhancers and silencers, a process vital for genome evolution, developmental control, and disease onset.
متن کاملVacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans.
BACKGROUND & AIMS The Helicobacter pylori toxin vacuolating cytotoxin (VacA) promotes gastric colonization, and its presence (VacA(+)) is associated with more-severe disease. The exact mechanisms by which VacA contributes to infection are unclear. We previously found that limited exposure to VacA induces autophagy of gastric cells, which eliminates the toxin; we investigated whether autophagy s...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Nature Genetics
سال: 2017
ISSN: 1061-4036,1546-1718
DOI: 10.1038/ng.3837