Dynamic mutation
Encyclopedia
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. These mutations, typically short sequences repeated many times, give rise to numerous known diseases including the Trinucleotide repeat disorders
.
Robert I. Richards and Grant R. Sutherland called these phenomena, in the framework of dynamical genetics
, dynamic mutations. Triplet expansion is caused by slippage during 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 paring between the parent strand and daughter strand being synthesized. If the loop out structure is formed from 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.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, 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. These mutations, typically short sequences repeated many times, give rise to numerous known diseases including the Trinucleotide repeat disorders
Trinucleotide repeat disorders
Trinucleotide repeat disorders are a set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where trinucleotide repeats in certain genes exceeding the normal, stable, threshold, which differs per gene...
.
Robert I. Richards and Grant R. Sutherland called these phenomena, in the framework of 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....
, dynamic mutations. Triplet expansion is caused by slippage during 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 paring between the parent strand and daughter strand being synthesized. If the loop out structure is formed from 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.
Common features
- Most of these diseases have neurological symptoms.
- AnticipationAnticipation (genetics)In genetics, anticipation is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation. In most cases, an increase of severity of symptoms is also noted. Anticipation is common in trinucleotide repeat disorders such as...
/The Sherman paradoxThe Sherman paradoxThe Sherman Paradox refers to an anomalous pattern of inheritance found in Fragile X syndrome. The phenomenon is also referred to as anticipation or dynamic mutation....
refers to progressively earlier or more severe expression of the disease in more recent generations. - Repeats are usually polymorphic in copy number, with mitotic and meiotic instability.
- Copy number related to the severity and/or age of onset
- Imprinting effects
- Reverse mutation - The mutation can revert to normal or to a premutation carrier state.
Examples
- Fragile X syndromeFragile X syndromeFragile X syndrome , Martin–Bell syndrome, or Escalante's syndrome , is a genetic syndrome that is the most commonly known single-gene cause of autism and the most common inherited cause of intellectual disability...
s - Huntington's Chorea
- Myotonic dystrophyMyotonic dystrophyMyotonic dystrophy is a chronic, slowly progressing, highly variable inherited multisystemic disease. It is characterized by wasting of the muscles , cataracts, heart conduction defects, endocrine changes, and myotonia. Myotonic dystrophy can occur in patients of any age...
- Spinobulbar muscular atrophy
- Spinocerebellar ataxiaSpinocerebellar ataxiaSpinocerebellar ataxia is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right.-Classification:...
type 3 - Friedreich ataxia
- Ocularpharyngeal muscular dystrophy
- Progressive myoclonus epilepsy