Drinking mutation
A truncating mutation is a gene mutation of a genome segment coding for a protein , resulting in a shortened gene product . Causes are nonsense mutations that a codon encoding into a stop codon transform but also frameshift mutation , which also alter the protein to follow in the new reading frames the first stop codon. Mutations that lead to the omission of an exon when the mRNA is spliced also result in shortened proteins. The effects on the cell can be very different. If the truncated protein has no function or is very unstable, the mutation cannot be distinguished from haploinsufficiency . At this phenotype may also be the nonsense mediated mRNA decay , which suppresses the formation of modified proteins contribute. This mechanism protects the cell from the harmful effects of truncated proteins. The truncated proteins can have a new (neomorphic) function and have dominant negative effects that cause disease. Dominant negative effects are found in proteins that dimerize or multimerize, such as B. the tumor suppressor P53 . In the case of P53, a mutated allele coding for a truncated molecule can cause tumors . Another disease mechanism is based on misdirected truncated proteins that lack signals for cellular localization. One example is truncated Neuroligin 4, which is thought to have a function in disrupting neuronal development .
swell
Walter Siegenthaler , Hubert Blum: Clinical Pathophysiology . Georg Thieme Verlag, Stuttgart 2006, ISBN 3134496097 , p. 32.
Individual evidence
- ↑ Amanda M Goh, Cynthia R Coffill, David P Lane: The role of mutant p53 in human cancer . In: The Journal of Pathology . 223, No. 2, 2011, ISSN 0022-3417 , pp. 116-126. doi : 10.1002 / path.2784 .
- ↑ Ben Chih, Shehla K Afridi, Lorraine Clark, Peter Scheiffele: Disorder-associated mutations lead to functional inactivation of neuroligins . In: Human Molecular Genetics . 13, No. 14, 2004, ISSN 1460-2083 , pp. 1471-1477. doi : 10.1093 / hmg / ddh158 .