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= Dynamic Mutation = Dynamic mutations are mutations that result in an unstable DNA sequence by expansion of existing polymorphic DNA repeat sequences across generations. The unstable DNA sequence produced as a result of these mutations is heritable and is increasing the levels of phenotypic variability in a population. The consequences of these repeat sequences depend on the genes that are affected and the location of these expansions. They could alter the gene transcription, structure, stability, protein structure and function and lead to diseases; including neurological and Trinucleotide repeat disorders. The length of the expansion repeat is correlated with disease severity and age of onset. There are 20 known human disorders related to dynamic mutations, the majority of these disorders are autosomal dominant and involve expansion of trinucleotide repeats. However, recessive or X-linked disorders and tetranucleotide and pentanucleotide repeat expansion have also been seen. Each disease have their own repeat number threshold, when the repeat number increase beyond that threshold the disease phenotype is observed.

Mechanisms
There are numerous processes and factors that affect the process of dynamic mutations and their stability. These factors are divided into two groups, cis-elements and trans-factors.

Cis-elements
Cis-elements are those directly associated with the expanding repeat. These could be internal, which includes the copy number and the composition of the repeat. Instability is related to repeat length, higher copy numbers with tandem repeats are more unstable. Also could be external, such as methylation, replication origins and flanking sequence elements.

Trans-factors
Trans factors are those interacting with instability of the repeats, for example DNA metabolism. Trans-acting factors are related to which parent transmits the mutations. The behavior of the mutation differs depending on the sex of the parent transmitting the gene. For the fragile X mutation, mothers can pass on the full mutation, however fathers who are carriers of the full mutation or affected themselves cannot pass it on to their offspring. This is an example of maternal expansion bias, and the mutations are mostly likely caused by high extended time for oogenic meiosis. The other kind is called paternal expansion bias, and the mutations are caused by mitotic cycles of spermatogenesis. In the juvenile onset form of Huntington disease and spinocerebellar ataxia type I the mutations are mostly inherited from the father.

Pathogenic Pathways
Most of these disorders involve gain of function mutation, however loss of function is also observed as well. Location of the repeat expansions play a huge role in the mechanism of pathogenesis.

Loss of function
There are two situations that might cause loss of gene function. The first one is interfering with transcription. In fragile X syndrome repeat extensions cause the FMR1 promoter to be methylated, which prevents the transcription of the gene. Other disease examples of this type of loss of function are myoclonus epilepsy and Friedreich's ataxia. The other situation is haploinsufficiency, which is the case of myotonic dystrophy. The promoter of the SIX5 gene is expanded; therefore when it does not function properly, causing a reduction of the required SIX5 gene dosage.

Gain of function
Gain of function also could be caused by two different situations. The first one involves expansion of repeats in translated regions that encode polyglutamine. These repeat expansions eventually cause polyglutamine tract and these expanded polyglutamines are toxic and change conformation accordingly. Also, expanded nucleotide repeats in the 5' UTR, 3'UTR and introns could also interact with the function of the gene. These untranslated repeats become toxic through RNA gain of function mechanism.