DNA Mutation and Disease

This post will talk about what happens when mutations occur in DNA. I'll be discussing what a mutation is, the different types of mutations, the causes of mutations, as well as the diseases associated with tri-nucleotide repeats.

What is a Mutation?

 A mutation is a permanent heritable change in the base pair sequence of genomic DNA (DNA found in an organism's genome and is passed on to offspring). Mutations can damage or change a gene in such a way as to alter the genetic message that is carried by that gene. The mutation is continued and preserved by replication and can occur anywhere in the genome. However, only mutations which occur in DNA which codes for proteins will have an observable effect.

DNA mutations can be good or bad. If the mutation is negative, disease may result. A mutation can be benign, an example is different eye colours. Mutations may also be positive such as how children with sickle shaped cells have lower rates of malaria infection. Mutations allow the gradual selective change of organisms, they are good for the population as a whole but may be bad for individuals.    

Types of Mutations

Point Mutations:

A point mutation is the exchange of a single nucleotide for another. Transition point mutations exist, where a purine is exchanged for a purine (A to G) or a pyrimidine for a pyrimidine (C to T). You can also get transversion point mutations, where a purine is exchanged for a pyrimidine or vice versa (C or T to A or G)

Point mutations that occur within a protein coding region of a gene may result in:  

• a silent mutation: where the mutation codes for the same amino acid.
• Missense mutation: where the mutation codes for a different amino acid. Sickle cell anaemia is caused by this type of point mutation.
• Nonsense mutation: where the mutation codes for a stop codon, which can truncate the protein. Progressive Retinal Atrophy in Irish Setters is an example of a disease caused by this type of mutation. 

Insertion/Deletion Mutations:

These involve either the insertion or removal of one or more bases. This results in the frame of mRNA read by the ribosomes to be altered, changing the protein produced. 

Frame shift Mutations: 

These mutations occur because of the insertion/deletion of a number of bases which cannot be divided by 3. For example, if the following sentence was a sequence of DNA and it was affected by a frame shift mutation:

The cow jumped over the moon.
            would become:
The coj umpedo vert hem oon.

 Chromosomal Mutations

These arise from errors in meiosis and include:

• Duplications: a piece of chromosome appears twice
• Inversions: a piece of chromosome turns 180 degrees
• Deletions: a piece of chromosome is missing.
• Translocations: a piece of chromosome attaches to another chromosome.        

Types of Chromosomal Mutations

What Causes Mutations?

Causes of mutations include:

• Chemicals: a chemical may resemble a purine or pyrimidine but a ineffective at base pairing, this causes DNA replication errors. An example is nitrogen mustard which was a component of mustard gas used in WWI and WWII. 
• Misalignment Mutagenesis: Acridine molecules insert between base pairs, increasing the space between them. This can cause the loss or gain of a single nucleotide during replication leading to frame-shift mutations.
• UV light: UV energy can cause adjacent thymines to be joined. This brings the base pairs closer which distorts the double helix. This blocks transcription and DNA replication.
• Ionising radiation: When ionising radiation comes into contact with living tissue or water free radicals are formed. These free radicals interact with DNA resulting in mutagenic and carcinogenic effects. 

Tri-nucleotide Repeats 

These are sequences of 3 bases repeated multiple times. For example: CAGCAGCAGCAG. Several genetic diseases are caused by these repeats including Huntington disease, Myotonic dystrophy, and Fragile X syndrome. 


That's all for this post, if you have any questions please don't hesitate to ask :)