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 Replication may refer to: Science * Replication (scientific method), one of the main principles of the scientific method, a.k.a. reproducibility ** Replication (statistics), the repetition of a test or complete experiment ** Replication crisi ...

product ( progeny) 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, also known as microsatellite expansion diseases, are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides ( trinucleotide repeats) inc ...

. Robert I. Richards and Grant R. Sutherland called these phenomena, in the framework of

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. The study of such mechanisms is important firstly since they pro ...

, 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 pairing 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. * Anticipation/

The Sherman paradox The Sherman paradox was a term used to describe the anomalous pattern of inheritance found in fragile X syndrome. The phenomenon is also referred to as anticipation or dynamic mutation. Background The paradox was named in the late 1980s after Am ...

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 syndrome Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features may ...

s * Huntington's disease * Myotonic dystrophy * Spinal and bulbar muscular atrophy * Spinocerebellar ataxia type 3 *

Friedreich ataxia Friedreich's ataxia (FRDA or FA) is an autosomal-recessive genetic disease that causes difficulty walking, a loss of sensation in the arms and legs, and impaired speech that worsens over time. Symptoms generally start between 5 and 20 year ...

*Ocularpharyngeal muscular dystrophy * Progressive myoclonus epilepsy

References

* Mutation {{genetics-stub