How many exons are in a DMD gene?
The dystrophin gene (DMD), with its 79 constitutive exons, and at least other 7 alternatively-used exons, is the largest known human gene, spanning 2.2 Mb of genomic DNA (Muntoni et al., 2003).
What happens if an exon is mutated?
Mutations in these sequences may lead to retention of large segments of intronic DNA by the mRNA, or to entire exons being spliced out of the mRNA. These changes could result in production of a nonfunctional protein.
What is the mutation in dystrophin?
A large and complex gene on the X chromosome encodes dystrophin. Many mutations have been described in this gene, most of which affect the expression of the muscle isoform, the best-known protein product of this locus. These mutations result in the Duchenne and Becker muscular dystrophies (DMD and BMD).
How do exon deletions occur?
Deletions occur when pieces of the gene (called exons) are missing. Deletions of one or more exons are the most common type of mutation. Since there are a total of 79 exons in the dystrophin gene, there are many different deletions that can occur.
What is exon 53 skipping?
About Vyondys 53 Exon skipping is a treatment strategy in which sections of genetic code are “skipped” (spliced out, or left out) during the protein manufacturing process, allowing cells to create shortened but partially functional dystrophin protein, the muscle protein missing in DMD.
How many mutations are in a DMD?
Scientists have recorded more than 1,800 mutations in the DMD gene in people with the Duchenne and Becker forms of muscular dystrophy.
How is exon skipping used to treat a genetic disease?
Most commonly, one or more exons (parts of the gene) are missing, causing errors in the instructions for making dystrophin. This results in the body not being able to produce enough—or any—working dystrophin protein. The goal of exon skipping is to allow the body to make a shorter form of the dystrophin protein.
What is exon inclusion?
It allows a gene to be transcribed into multiple isoforms (or mRNA transcripts) and hence increases the phenotypic complexity of an organism without increasing its genetic complexity. The exon-inclusion ratio, also known as percent spliced in (PSI), is a popular statistic for measuring alternative splicing events (2).
Why Does gene duplication occur?
Gene duplication is the process by which a region of DNA coding for a gene is copied. Gene duplication can occur as the result of an error in recombination or through a retrotransposition event. Duplicate genes are often immune to the selective pressure under which genes normally exist.
Why does exon skipping occur?
What is exon skipping? Duchenne is caused by a genetic mutation in the dystrophin gene. Most commonly, one or more exons (parts of the gene) are missing, causing errors in the instructions for making dystrophin. This results in the body not being able to produce enough—or any—working dystrophin protein.
Which is the biggest duplication in human DNA?
A duplication occurs when more than one letter is duplicated in the DNA code. The dystrophin gene is the biggest in human cells – the DNA code is more than 10,000 letters long and duplications can range in size from just a few letters to many thousands of letters. Duplications cause approximately 10% of cases of Duchenne.
How often are duplications detected in the DMD gene?
In an unselected patient series the duplication frequency was 7%. In patients already screened for deletions and point mutations, duplications were detected in 87% of cases. There were four complex, noncontiguous rearrangements, with two also involving a partial triplication.
How big is a duplication in Duchenne muscular dystrophin?
In Duchenne, duplications are often so big that they are described by exon number (for example you might hear “exon 2 duplication”). An exon is part of a gene which must be pieced together by a cell to produce a protein. The dystrophin gene has 79 exons and any combination of exons could be dupicated.
What are the mutations in the dystrophin gene?
Duchenne is a genetic condition. This means the condition is caused by genetic mutations – alterations or changes – in a gene. Duchenne is caused by mutations in a single gene called the dystrophin gene. These mutations prevent cells from producing the dystrophin protein which is needed for muscle function.