Dr. Israa ayoub alwan Lec -10- AL-Ma’moon University College Medical Laberatory techniques Department Molecular biology/ Second stage Dr. Israa ayoub alwan Lec -10-

Types of Mutations

Mutations can be classified by whether they remove, alter, or add a function, or by exactly how they structurally alter DNA. The same single-gene disorder can result from different types of mutations, 1. Point Mutations 2. .Missense Mutations 3. nonsense mutation 4. Deletions and Insertions

1. Point Mutations is a change in a single DNA base. It is a transition if a purine replaces a purine (A to G or G to A) or a pyrimidine replaces a pyrimidine (C to T or T to C). It is a transversion if a purine replaces a pyrimidine or vice versa (A or G to T or C). A point mutation can have any of several consequences—or it may have no obvious effect at all on the phenotype, acting as a silent mutation.

2.Missense Mutations A point mutation that changes a codon that normally specifies a particular amino acid into one that codes for a different amino acid is called a missense mutation. If the substituted amino acid alters the protein’s conformation significantly or occurs at a site critical to its function, signs or symptoms of disease or an observable variant of a trait may result. About a third of missense mutations harm health. The point mutation that causes sickle cell disease is a missense mutation. The DNA sequence CTC encodes the mRNA codon GAG, which specifies glutamic acid. In sickle cell disease, the mutation changes the DNA sequence to CAC, which encodes GUG in the mRNA, which specifies valine. This mutation changes the protein’s shape, which alters its function.

3. nonsense mutation A point mutation that changes a codon specifying an amino acid into a “stop” codon—UAA, UAG, or UGA in mRNA—is a nonsense mutation. A premature stop codon shortens the protein product, which can greatly influence the phenotype. For example, in factor XI deficiency (MIM 264900), a blood clotting disorder, a GAA codon specifying glutamic acid is changed to UAA, signifying “stop.” The shortened clotting factor cannot halt the profuse bleeding that occurs during surgery or from injury. Nonsense mutations are predictable by considering which codons can mutate to a “stop” codon. In the opposite of a nonsense mutation, a normal stop codon mutates into a codon that specifies an amino acid. The resulting protein is longer than normal, because translation continues through what is normally a stop codon.

4.Deletions and Insertions In genes, the number 3 is very important, because triplets of DNA bases specify amino acids. Adding or deleting a number of bases that is not a multiple of three devastates a gene’s function because it disrupts the gene’s reading frame, which refers to the nucleotide position where the DNA begins to encode protein . An exon is usually “readable” (has no stop codons) in only one of its three possible reading frames. A change that alters the reading frame is called a frameshift mutation.  

A deletion mutation removes genetic material A deletion mutation removes genetic material. A deletion that removes three or a multiple of three bases will not cause a frameshift, but can still alter the phenotype. Deletions range from a single DNA nucleotide to thousands of bases to large parts of chromosomes. Many common inherited disorders result from deletions, including male infertility caused by tiny deletions in the Y chromosome.

An insertion mutation adds DNA and it, too, can offset a gene’s reading frame. In one form of Gaucher disease, for example, an inserted single DNA base prevents production of an enzyme that normally breaks down glycolipids in lysosomes. The resulting buildup of glycolipid enlarges the liver and spleen and causes easily fractured bones and neurological impairment. Another type of insertion mutation repeats part of a gene’s sequence. The insertion is usually adjacent or close to the original sequence, like a typographical error repeating a word word. Two copies of a gene next to each other is called a tandem duplication.

These three mutations exert very different effects on the protein These three mutations exert very different effects on the protein. A missense mutation replaces one amino acid with another, bending the protein in a way that impairs its function. A nonsense mutation greatly shortens the protein. A frameshift mutation introduces a section of amino acids that is not in the wild type protein.

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