Anticipation (genetics)
In
Trinucleotide repeats and expansion
Trinucleotide repeats are apparent in a number of
The mechanism behind the expansion of the triplet repeats is not well understood. One hypothesis is that the increasing number of repeats influences the overall shape of the DNA, which can have an effect on its interaction with DNA polymerase and thus the expression of the gene.[citation needed]
Disease mechanisms
For many of the loci, trinucleotide expansion is harmless,[
In order to have a deleterious effect, the number of repeats must cross a certain threshold. For example, normal individuals have between 5 and 30 CTG repeats within the 3' UTR of DMPK, the gene that is altered in myotonic dystrophy. If the number of repeats is between 50 and 100, the person is only mildly affected – perhaps having only cataracts. However, meiotic instability could result in a dynamic mutation that increases the number of repeats in offspring inheriting the mutant allele. Once the number of copies reaches over 100, the disease will manifest earlier in life (although the individual will still reach adulthood before the symptoms are evident) and the symptoms will be more severe – including electrical myotonia. As the number progresses upwards past 400, the symptoms show themselves during childhood or infancy.[citation needed]
Examples of diseases showing anticipation
Diseases showing anticipation include:
- Autosomal dominant
- Several spinocerebellar ataxias
- Huntington's disease – CAG
- Myotonic dystrophy – CTG
- Dyskeratosis congenita – TTAGGG (telomere repeat sequence)[1]
- Several
- Autosomal recessive
- Friedreich ataxia – GAA (Note: Friedreich ataxia does not usually exhibit anticipation because it is an autosomal recessive disorder.[2])
- X-linked
- Fragile X syndrome – CGG
- Without expression type
References
External links
- Genetic+anticipation at the U.S. National Library of Medicine Medical Subject Headings (MeSH)