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Whenever there is a change in the structure or amount of DNA in an organism, it is called a mutation. There are a number of different types of mutations, depending on where the change occurs and how the DNA is affected. A nonsense mutation is a single base substitution, or point mutation. When a nonsense mutation occurs, only one base is changed in the DNA strand.
DNA is made up of a double helix of long strands of nucleotides that have nitrogenous bases attached to them. The four bases are adenine, thymine, guanine and cytosine. The nucleotides are joined together to form long polynucleotide strands. The two strands are held together by hydrogen bonds between complementary base pairs.
Each base is either a purine base or a pyrimidine base depending on the number of chemical rings in its molecular structure. Purine bases have two chemical rings and include adenine and guanine. Pyrmidine bases have only one chemical ring and include cytosine and thymine. The purine bases always base pair with the pyrimidine bases, or more specifically, adenine with thymine and cytosine with guanine.
When proteins are synthesized in a cell, the information for each protein is carried in the genes along the DNA strands. A triplet of bases, or codon, in a gene codes for a specific amino acid, which is a building blocks for protein molecules. The sequence of amino acids to be used to form a protein is determined by the sequence of the codons. Any changes in these codons, if not repaired, can affect the protein being formed.
To form a protein, two processes occur. First, the DNA is transcribed into messenger RNA (mRNA) within the nucleus. mRNA is a single stranded molecule so it is able to leave the nucleus through small holes, or pores, in the nuclear membrane. The mRNA now carries the information for synthesizing a protein during translation in the cytoplasm of the cell.
Nonsense mutations affect the genetic coding region of the DNA. When a nonsense mutation occurs, one base is changed so that the triplet code for its amino acid changes to code for a stop codon. The stop codons are TTA, TAG or TGA. A nonsense mutation causes the transcription of the DNA into mRNA to stop, which means that the mRNA strand is shorter than it should be. The earlier in the gene this mutation occurs, the shorter the mRNA and the more truncated the protein will be, making it less likely to function.
There are a number of genetic disorders that are caused by nonsense mutations. Cystic fibrosis is caused by mutations in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Some patients have a nonsense mutation in the gene, which causes a large part of the protein to not be formed. Any defects in this protein cause the different symptoms of the condition. Other conditions that can be caused by nonsense mutations include Duchenne muscular dystrophy, Beta thalassemia and Hurler syndrome.
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