User:Musicalkeer/Frameshift mutation

A frameshift mutation, also known as a reading frameshift or a framing error, occurs when a set of nucleotides is added or removed from a DNA sequence, causing an uneven division by three.

This leads to two primary categories of mutations: Insertion and Deletion. Insertion involves the addition of one or more nucleotides, resulting in a shift in the reading frame and a completely different protein sequence. For instance, introducing an extra "A" causes a sequence shift, altering the codon sequence read. On the other hand, Deletion occurs when one or more nucleotides are removed, also resulting in a change in the reading frame and the formation of a distinct protein. I have edited some of the points in frameshift mutation.

Background:

Genetic information is conveyed by DNA for protein synthesis within cells. Misinterpretation can lead to faulty function and disease, despite cellular correction mechanisms.

Central Dogma:

In 1956, Francis Crick established the central dogma, which describes the transmission of genetic information from DNA to protein synthesis synthesis. Accurate protein production is crucial for cell function, influencing both structure and catalytic activities. Errors in protein synthesis can detrimentally affect cell health and overall organism well-being due to abnormal cellular functions. To ensure accurate information transfer, DNA replication incorporates proofreading mechanisms like exonucleases and mismatch repair systems.

Mechanism:

In an unaltered gene, codons (triplets of nucleotides) are sequentially interpreted, with each codon encoding a specific amino acid. This is known as the standard reading frame. However, in cases of frame shift mutations, an extra nucleotide (or more) is inserted into the DNA sequence, disrupting the typical reading frame and causing a shift in the sequence.

This insertion prompts a shift in the reading frame due to the triplet nature of the genetic code. For instance, the addition of an extra "A" leads to a sequence shift, triggering the reading of an entirely different set of codons. This deviation in genetic information causes the ribosome, which reads the mRNA for protein synthesis, to misinterpret the genetic data. Consequently, an entirely different series of amino acids is generated, resulting in the generation of an altered protein sequence. In most instances, the new reading frame results in an early encounter with a stop codon, leading to the formation of a shortened and usually inactive protein. This form of mutation is termed an early stop codon or a nonsense mutation.

Diagnosis: DNA Sequencing: Sanger sequencing or Next-Generation Sequencing (NGS) can be used to directly sequence the DNA and identify insertions or deletions.

Polymerase Chain Reaction (PCR): PCR can be used to amplify the specific region containing the mutation for subsequent analysis.

Multiplex Ligation-dependent Probe Amplification (MLPA): MLPA is a technique used to detect copy number variations and small insertions or deletions.

Comparative Genomic Hybridization (CGH): CGH is used to detect chromosomal imbalances, which may include large insertions or deletions.

Treatment and Interventions:

Depending on the specific mutation and associated disorder, various treatment strategies may be considered. These could encompass gene therapy, gene editing techniques like CRISPR, or other targeted therapies.

References:

1. Krawczak, M., Ball, E. V., & Cooper, D. N. (1998). Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. American journal of human genetics, 63(2), 474–488. https://doi.org/10.1086/301965

2. Mardis E. R. (2008). Next-generation DNA sequencing methods. Annual review of genomics and human genetics, 9, 387–402. https://doi.org/10.1146/annurev.genom.9.081307.164359

3.McDonald-McGinn, D. M., & Sullivan, K. E. (2011). Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine, 90(1), 1–18. https://doi.org/10.1097/MD.0b013e3182060469