Short tandem repeats (STRs), or microsatellites, are 1-6 base pair (bp) motifs of repeating units of DNA. (biomedcentral.com)
Genome7
Many regions of the genome (exons, introns, intergenic regions) normally contain trinucleotide sequences, or repeated sequences of one particular nucleotide, or sequences of 2, 4, 5 or 6 nucleotides. (wikipedia.org)
Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. (biomedcentral.com)
To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. (biomedcentral.com)
Approximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. (biomedcentral.com)
We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants. (biomedcentral.com)
Some of these tools are designed to detect STR expansions at disease-related loci, while others detect expansions and contractions of STRs genome-wide but are constrained by sequencing read length and the STR motif size. (biomedcentral.com)
New technologies such as next-generation sequencing (including whole exome or whole genome sequencing) are expanding testing options, discovering new mutations, and creating challenges in counseling, interpreting, and reporting results to the patient. (medlink.com)
An increase number of repeats of a genomic, tandemly repeated DNA sequence from one generation to the next. (uams.edu)
Occur2
What this slide shows is that these types of mutations can occur in various parts of the gene. (hstalks.com)
Some occur in the coding region of the gene, others occur in the five prime region and others occur in the three prime region, and these have different consequences on the function of the gene and the results of the mutation. (hstalks.com)
Fragile X syndro2
The first trinucleotide repeat disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. (wikipedia.org)
Patients carry from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome, while unaffected individuals have up to 50 repeats and carriers of the disease have 60 to 230 repeats. (wikipedia.org)
Diseases4
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 cause developmental, neurological or neuromuscular disorders. (wikipedia.org)
Today I'm going to tell you about microsatellites, and trinucleotide repeat expansions diseases. (hstalks.com)
These diseases are all caused by microsatellite mutations, where a microsatellite either has three bases, four bases, five bases, or six bases, and these mutations result in excess numbers of copy of these particular units. (hstalks.com)
Because of the number of diseases in this slide, I've chosen to focus on those in boxes for the most part, and I've chosen to focus on them because I think they illustrate the key genetic principles underlying this class of mutation. (hstalks.com)
Chromosome3
The second DNA-triplet repeat disease, fragile X-E syndrome, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. (wikipedia.org)
For instance, if you've got a mutation caused by triplet repeat expansion, for instance in the Huntington's gene, where the trinucleotide repeats a CAG, you might have 17 CAGs in a normal chromosome. (hstalks.com)
But in a diseased chromosome, you might have 40 successive copies of CAG trinucleotides in the gene. (hstalks.com)
Slippage1
It is possible that each of these mechanisms contributes to the high mutation rate of STRs, but strand slippage is the mechanism proposed for generating most observed mutations in STR loci [ 19 ]. (biomedcentral.com)
Disorders6
Trinucleotide repeat disorders and the related microsatellite repeat disorders affect about 1 in 3,000 people worldwide. (wikipedia.org)
Three categories of trinucleotide repeat disorders and related microsatellite (4, 5, or 6 repeats) disorders are described by Boivin and Charlet-Berguerand. (wikipedia.org)
The second main category of trinucleotide repeat disorders and related microsatellite disorders involves a toxic RNA gain of function mechanism. (wikipedia.org)
The third main category of trinucleotide repeat disorders and related microsatellite disorders is due to the translation of repeat sequenced into pathogenic proteins containing a stretch of repeated amino acids. (wikipedia.org)
Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders. (medlink.com)
Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions. (medlink.com)
Copies1
Sometimes, a person may have more than the usual number of copies of a repeat sequence associated with a gene, but not enough to alter the function of that gene. (wikipedia.org)
Mechanisms2
This results in, variously, a toxic gain of function, a loss of function, a dominant negative effect and/or a mix of these mechanisms for the protein hosting the expansion. (wikipedia.org)
Translation of these repeat expansions occurs mostly through two mechanisms. (wikipedia.org)
Results1
The results in PAR1/PAR2 are the first large-scale studies of gene dosage in these regions, and the findings at the ASMT locus indicate that further studies of the duplication of the ASMT gene are needed in order to gain insight into its potential involvement in ASD. (biomedcentral.com)
Large1
In this second type of disorder, large repeat expansions in DNA are transcribed into pathogenic RNAs that form nuclear RNA foci. (wikipedia.org)
Parent2
The discovery that trinucleotide repeats could expand during intergenerational transmission and could cause disease was the first evidence that not all disease-causing mutations are stably transmitted from parent to offspring. (wikipedia.org)
Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. (biomedcentral.com)
Disease4
In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes. (wikipedia.org)
The epigenetic alterations and their effects are described more fully by Barbé and Finkbeiner These authors cite evidence that the age at which an individual begins to experience symptoms, as well as the severity of disease, is determined both by the size of the repeat and the epigenetic state within the repeat and around the repeat. (wikipedia.org)
One individual was found to carry a 12 kb deletion in one copy of the ASPA gene on 17p13, which when mutated in both alleles leads to Canavan disease. (biomedcentral.com)
the background rate of point mutations [2]. (scirp.org)
Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10 −5 mutations per locus per generation. (biomedcentral.com)
We use HipSTR to identify de novo STR mutations in the 2nd generation of these pedigrees and require transmission to the third generation for validation. (biomedcentral.com)
Features1
The chromosomal instability resulting from this trinucleotide expansion presents clinically as intellectual disability, distinctive facial features, and macroorchidism in males. (wikipedia.org)
Shows1
This graph shows the total number of publications written about "DNA Repeat Expansion" by people in UAMS Profiles by year, and whether "DNA Repeat Expansion" was a major or minor topic of these publications. (uams.edu)
Region2
The first main category these authors discuss is repeat expansions located within the promoter region of a gene or located close to, but upstream of, a promoter region of a gene. (wikipedia.org)
A partial duplication in the ASMT gene, located in the pseudoautosomal region 1 (PAR1) of the sex chromosomes and previously suggested to be involved in ASD susceptibility, was observed in 6-7% of the cases but in only 2% of controls (P = 0.003). (biomedcentral.com)
People1
Below are the most recent publications written about "DNA Repeat Expansion" by people in Profiles over the past ten years. (uams.edu)
Levels1
Some carriers, during the formation of eggs or sperm, may give rise to higher levels of repetition of the repeat they carry. (wikipedia.org)
Found1
Two subjects showed partial duplication of the TM4SF2 gene on Xp11.4, previously implicated in X-linked non-specific mental retardation, but in our subsequent analyses such variants were also found in controls. (biomedcentral.com)