Trinucleotide repeat expansion
Encyclopedia
Trinucleotide repeat expansion, also known as triplet repeat expansion, is the DNA
mutation
responsible for causing any type of disorder
categorized as a trinucleotide repeat disorder. These are labelled in dynamical genetics
as dynamic mutation
s. Triplet expansion is caused by slippage during DNA replication, also known as "copy choice" DNA replication. Due to the repetitive nature of the DNA sequence in these regions, 'loop out' structures may form during DNA replication while maintaining complementary base pairing between the parent strand and daughter strand being synthesized. If the loop out structure is formed from the sequence on the daughter strand this will result in an increase in the number of repeats. However, if the loop out structure is formed on the parent strand, a decrease in the number of repeats occurs. It appears that expansion of these repeats is more common than reduction. Generally, the larger the expansion the more likely they are to cause disease or increase the severity of disease. This property results in the characteristic of anticipation seen in trinucleotide repeat disorders. Anticipation describes the tendency of age of onset to decrease and severity of symptoms to increase through successive generations of an affected family due to the expansion of these repeats.
In 2006, a model of expanding the triplets by involving RNA:DNA intermediate formed in repeat transcription or in post-transcription was proposed. and similar ideas turned to be a fashion ongoing issue of the mechanism studies ever since
. In 2007, a new disease model was produced to explain the progression of Huntington's Disease
and similar trinucleotide repeat disorders, which, in simulations, seems to accurately predict age of onset and the way the disease will progress in an individual, based on the number of repeats of a genetic mutation
.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
responsible for causing any type of disorder
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
categorized as a trinucleotide repeat disorder. These are labelled in dynamical genetics
Dynamical genetics
Dynamical genetics concerns the study and the interpretation of those phenomena in which physiological enzymatic protein complexes alter the DNA, in a more or less sophisticated way....
as dynamic mutation
Dynamic mutation
In genetics, a dynamic mutation is an unstable heritable element where the probability of expression of a mutant phenotype is a function of the number of copies of the mutation. That is, the replication product of a dynamic mutation has a different likelihood of mutation than its predecessor...
s. Triplet expansion is caused by slippage during DNA replication, also known as "copy choice" DNA replication. Due to the repetitive nature of the DNA sequence in these regions, 'loop out' structures may form during DNA replication while maintaining complementary base pairing between the parent strand and daughter strand being synthesized. If the loop out structure is formed from the sequence on the daughter strand this will result in an increase in the number of repeats. However, if the loop out structure is formed on the parent strand, a decrease in the number of repeats occurs. It appears that expansion of these repeats is more common than reduction. Generally, the larger the expansion the more likely they are to cause disease or increase the severity of disease. This property results in the characteristic of anticipation seen in trinucleotide repeat disorders. Anticipation describes the tendency of age of onset to decrease and severity of symptoms to increase through successive generations of an affected family due to the expansion of these repeats.
In 2006, a model of expanding the triplets by involving RNA:DNA intermediate formed in repeat transcription or in post-transcription was proposed. and similar ideas turned to be a fashion ongoing issue of the mechanism studies ever since
. In 2007, a new disease model was produced to explain the progression of Huntington's Disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
and similar trinucleotide repeat disorders, which, in simulations, seems to accurately predict age of onset and the way the disease will progress in an individual, based on the number of repeats of a genetic mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
.