What problems do the expanded repeats cause in the cell?
These repetitive sequences lead to instability amongst the DNA strands after reaching a certain threshold number of repeats, which can result in DNA slippage during replication. The most common and well-known triplet repeats are CAG, GCG, CTG, CGG, and GAA.
What are trinucleotide repeats and when can they be problematic?
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) increase in copy numbers until they cross a threshold above which they become …
Which of these diseases is caused by a trinucleotide repeat expansion?
At least seven disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington’s disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA).
How are trinucleotide repeats detected?
The RED method was developed to enable detection of expanded trinucleotide repeat sequences in any DNA sample from any species without prior knowledge of the DNA sequences flanking the repeat. The DNA to be tested is used as a template for a repeat oligonucleotide to anneal and ligate in a two-step cycling procedure.
Why does trinucleotide repeat expansion occur?
The mutation, referred to as “trinucleotide repeat (TNR) expansion,” occurs when the number of triplets present in a mutated gene is greater than the number found in a normal gene [1–3]. Additionally, the number of triplets in the disease gene continues to increase as the disease gene is inherited (Fig.
How do trinucleotide repeats expand?
As shown in the animation, trinucleotide repeats can expand due to slippage during DNA replication. The number of repeats can therefore increase with each cell division. Expanded repeats are also inherited and can grow longer over multiple …
How does trinucleotide repeat expansion occur?
The mutation, referred to as “trinucleotide repeat (TNR) expansion,” occurs when the number of triplets present in a mutated gene is greater than the number found in a normal gene [1–3]. Additionally, the number of triplets in the disease gene continues to increase as the disease gene is inherited (Fig. 1a).
What causes repeat expansion?
Repeat expansion diseases include both causes of myotonic dystrophy (DM1 and DM2), the most common genetic cause of amyotrophic lateral sclerosis/frontotemporal dementia (C9ORF72), Huntington disease and eight other polyglutamine disorders including the most common forms of dominantly inherited ataxia, the most common …
What is trinucleotide repeat?
Listen to pronunciation. (try-NOO-klee-oh-tide reh-PEET) Sequences of 3 nucleotides repeated in tandem on the same contiguous section of chromosome.
How do you identify tandem repeats?
Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadillo repeats.
What are expanded trinucleotide repeat diseases?
Expanded trinucleotide repeat diseases were discovered first and remain the most frequent. More recently tetra-, penta-, hexa- and even dodeca-nucleotide repeat expansions have been identified as the cause of human disease, including some of the most common genetic disorders seen by neurologists.
Why are large trinucleotide expansions unstable?
However, in large repeat expansions, the repair is error-prone that results in changes of triplet repeat length and can contribute to TRNI [180, 181]. The instability of long trinucleotide expansions is triggered by strand separation during replication, transcription, recombination, or supercoiling [182].
Are unstable trinucleotide repeats associated with increased size during gametogenesis?
Unstable trinucleotide repeats are a novel disease mechanism, first discovered in 1991, and an important cause of neurogenetic disease. A feature of these conditions is anticipation, with earlier onset and more severe phenotype in successive generations, which appears to correlate with increasing repeat size during gamete formation.
What are the complications of trinucleotide repeat disorders?
Most trinucleotide repeat disorders have a wide spectrum of complications, ranging from debilitating physical disabilities like ataxia, chorea, severe muscle weakness, connective tissue defects to lethal complications like cardiomyopathy, diaphragmatic weakness, severe depression, etc, depending on the kind of repeat disorder.