What causes CAG expansion?
Table of Contents
What causes CAG expansion?
These are caused by a CAG repeat expansion in protein-coding portions, or exons, of specific genes….Polyglutamine (PolyQ) diseases.
| Type | SCA2 (Spinocerebellar ataxia Type 2) |
|---|---|
| Gene | ATXN2 |
| Normal PolyQ repeats | 14 – 32 |
| Pathogenic PolyQ repeats | 33 – 77 |
What is polyglutamine disease?
The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative diseases that are caused by the abnormal expansion of a CAG triplet repeat (above 35–40 repeats) in the coding region within the causative gene of each disease.
What is polyglutamine expansion?
Polyglutamine diseases are a large group of inherited neurodegenerative disorders caused by the expansion of the CAG trinucleotide, encoding the amino acid glutamine, in the coding region of different and functionally unrelated genes (Zoghbi and Orr, 2000).
What is PolyQ expansion in a protein?
PolyQ expansion in the translated proteins promotes their self-assembly into a variety of oligomeric and fibrillar aggregate species that accumulate into the hallmark proteinaceous inclusion bodies associated with each disease.
What does CAG stand for in genetics?
These bases have names: Adenine, Thymine, Guanine, and Cytosine. The gene responsible for HD contains a sequence with several CAG repeats (Cytosine, Adenine, Guanine).
What is CAG sequence?
The DNA sequence CAG encodes the amino acid glutamine. The CAG repeats in HTT therefore lead to the production of a string of glutamines, known as a polyglutamine chain, which is abnormally long in people with the large numbers of repeats that are associated with Huntington’s disease.
How is polyglutamine formed?
Formation of unusual structures by repetitive DNA seems to be a core mechanism of repeat instability which leads to elongated polyglutamine tracts. Proteins resulting from defective genes aggregate both in the cytoplasm and in the nucleus. They are cleaved before entering the nuclei.
What is the role of polyglutamine expansion in the development and progression of Huntington’s disease HD?
The polyQ expansion makes Htt prone to aggregate and accumulate, and manipulations that mitigate protein misfolding or facilitate the clearance of misfolded proteins tend to slow disease progression in HD models.
What causes polyglutamine disease?
Polyglutamine diseases are a family of neurodegenerative conditions that each derive from a CAG triplet repeat expansion in a specific gene. This produces a pathogenic protein that contains a critically expanded tract of glutamines.
What are polyglutamine proteins?
The polyglutamine (polyQ) diseases are a group of neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding a long polyQ tract in the respective proteins.
What is CAG in Huntington’s?
Some facts about genetics and Juvenile Huntington’s: The faulty version of the gene repeats a particular coding sequence known as CAG (cytosine-adenine-guanine) too many times – a bit like adding too much of one ingredient in a recipe. This means the protein it makes damages nerve cells in the brain.
What is CAG length?
The unstable CAG repeat in HD patients lies in exon 1 of the HTT gene on chromosome 4p16. 3. The CAG repeat length at this locus in the normal population ranges from 10 to 35, whereas in patients with HD, it ranges from 36 to 121, with a reduced penetrance at repeat sizes of 36–39.
Where is CAG located?
Fort Bragg, North Carolina, U.S.
Where are CAG repeats located?
The disease is caused by a CAG trinucleotide repeat expansion located in the first exon of the HD gene. The CAG repeat is highly polymorphic and varies from 6 to 37 repeats on chromosomes of unaffected individuals and from more than 30 to 180 repeats on chromosomes of HD patients.
What is CAG gene?
The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG trinucleotide repeat . This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene.
What is a CAG number?
The number of CAG repeats in the HD gene determines whether or not someone will develop HD during their lifetime. Everyone has two copies of the HD gene – one from their father and one from their mother.
What is CAG in the military?
For years, the military has delicately referred to this special missions unit (SMU) as “CAG,” which stands for “Combat Applications Group (Airborne).”
What does CAG mean in Huntington’s?
The gene responsible for HD contains a sequence with several CAG repeats (Cytosine, Adenine, Guanine). We all have these CAG repeats in the gene that codes for the huntingtin protein, but people with HD have a greater number than usual of CAG repeats in one of the genes they inherited.
What is variable expression in genetics?
Although some genetic disorders exhibit little variation, most have signs and symptoms that differ among affected individuals. Variable expressivity refers to the range of signs and symptoms that can occur in different people with the same genetic condition.
