genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...

, 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 ( 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 In genetics, trinucleotide repeat disorders, a subset of microsatellite expansion diseases (also known as repeat expansion disorders), are a set of over 30 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which r ...

. 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 In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...

. 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 Anticipation is an emotion involving pleasure or anxiety in considering or awaiting an expected event. Anticipatory emotions include fear, anxiety, hope, and trust. When the anticipated event fails to occur, it results in disappointment (for ...

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 Anticipation is an emotion involving pleasure or anxiety in considering or awaiting an expected event. Anticipatory emotions include fear, anxiety, hope, and trust. When the anticipated event fails to occur, it results in disappointment (for ...

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 A ...

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 neurodevelopmental disorder. The average IQ in males with FXS is under 55, while affected females tend to be in the borderline to normal range, typically around 70–85. Physical features may include a lo ...

s *

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...

Myotonic dystrophy Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness. In DM, muscles are often myotonia, unable to relax after contraction. Other manifestations may include catarac ...

Spinal and bulbar muscular atrophy Spinal and bulbar muscular atrophy (SBMA), popularly known as Kennedy's disease, is a rare, adult-onset, X-linked recessive lower motor neuron disease caused by trinucleotide CAG repeat expansions in exon 1 of the androgen receptor (AR) gene, whi ...

* Spinocerebellar ataxia type 3 *

Friedreich ataxia Friedreich's ataxia (FRDA) is a rare, inherited, autosomal recessive neurodegenerative disorder that primarily affects the nervous system, causing progressive damage to the spinal cord, peripheral nerves, and cerebellum, leading to impaired ...

* Ocularpharyngeal muscular dystrophy *

Progressive myoclonus epilepsy Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are ...

References

* Mutation {{genetics-stub