What Are Mutations?

Mutations
MOLT-13 and MOLT-13 boost DNA and cDNA sequencing analysis. (A) MOLT-13 TP53-sequencing. 1. DNA analysis shows a heterozygous mutation in codon 273 (TP53, exon 8, CGT > CAT, Arg > His) and a heterozygous polymorphism in codon 72 (TP53, exon 4, CGC > CCC, Arg > Pro), identical ratio of wild type to mutated template was detected. 2. cDNA sequencing confirms DNA results. (B) MOLT-13 boost TP53-sequencing. 1. DNA analysis shows a heterozygous mutation in codon 273 and, surprisingly, a deletion of one nucleotide - a nonsense mutation - in exon 4 (both wild type and mutated template are visible). 2. cDNA analysis showed only mutated nucleotide in codon 273 (representing hemizygous mutation) and only one allele expression in exon 4. These results suggest a missense mutation of one allele and a nonsense mutation of the other causing the nonsense mRNA decay. (C) FBXW7 and N-RAS DNA sequencing. In order to confirm MOLT-13 cell line identity, mutations of FBXW7 and N-RAS gene were verified. 1. FBXW7 analysis shows a heterozygous mutation in codon 465 (FBXW7, CGT > CAT, Arg > His). 2. N-RAS sequencing shows a heterozygous mutation in codon 12 (N-RAS, GGT > GAT, Gly > Asp). Mutations are marked with arrows. N - normal, control template. Limited importance of the dominant-negative effect of TP53 missense mutations. Stoczynska-Fidelus E, Szybka M, Piaskowski S, Bienkowski M, Hulas-Bigoszewska K, Banaszczyk M, Zawlik I, Jesionek-Kupnicka D, Kordek R, Liberski PP, Rieske P - BMC cancer (2011). Not Altered. CC.

Mutations are alterations in the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA.

Examples of mutations include:

  • Point mutations
  • Mutations in noncoding sequences
  • Mutations in introns
  • Mutations in exons
  • Deletions
  • Insertions
  • Trinucleotide repeats
Point mutationsA point mutation is alteration of a single base pair. The base substitution can be a silent mutation, which produces the same amino acid. The base substitution can be a missense mutation where the altered codon produces a different amino acid. The base substitution can be a nonsense mutation where a stop signal is produced.– Point mutations are present in multiple tumor suppressor proteins cause cancer. Adenomatous Polyposis Col. Neurofibromatosis. Sickle-cell anemia
Mutations in noncoding sequencesMutation in components of an organism’s DNA that do not actually code protein sequences.– PTF1A enhancer mutation can cause Pancreatic agenesis.– RET enhancer mutation can cause Hirshsprung disease.
Mutations in intronsMutations in intervening noncoding segments of DNA.A splice site mutation produces the parathyroid hormone.
Mutations in exonsMutation in part of a gene that will encode a part of the final RNA.Many issues.
DeletionsDeletion is a mutation that results in loss of genetic material. Deletions can be small or large.-DiGeorge syndrome – 22q11 deletion.-Cri-du-chat syndrome – microdeletion on the short arm of chromosome 5.-Williams syndrome – microdeletion of long arm of chromosome 7.
InsertionsAddition of one or more nucleotide base pairs into a DNA sequence.Huntington’s diseaseFragile X syndrome
Trinucleotide repeatsTrinucleotide repeat expansions are a type of mutation where trinucleotide repeats in certain genes or introns exceed the normal, stable threshold.– Fragile X syndrome – CGG repeats in fragile X mental retardation 1 (FMR1) gene.– Huntington’s disease – autosomal dominant trinucleotide CAG repeat expansion on chromosome 4.
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Last updated on May 25, 2022