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Printable Handouts
Navigable Slide Index
- Introduction
- Overview
- General features of repeat expansion diseases
- Primary mechanism of disease
- Fragile X Syndrome
- Fragile X
- Fragile X and normal transmitting males
- Likelihood of premutation expansion
- Parent-of-origin bias
- Myotonic dystrophy
- DM CTG repeats
- Molecular explanation for anticipation
- Regression of onset in myotonic patients
- Expansions between blood and sperm
- Somatic mosaicism – mitotic instability
- Somatic instability in blood of DM repeats
- Huntington’s disease
- Age of onset and CAG repeats
- Parent-child transmission and CAG size
- Zone of variable penetrance
- Interruptions lost
- Interruptions gained
- Inclusions in HD patients’ neurons
- Friedreich’s ataxia
- FA alleles
- Relationship of repeats to clinical features
- C9orf72 ALS & FTD: GGGGCC repeat in exon 1
- C9orf72 – gain and loss of function?
- Take home messages
Topics Covered
- Mendelian neurodegenerative diseases are caused by repeat expansions
- The mutation can result in gain-of-function or loss-of-function
- Fragile X syndrome
- Myotonic dystrophy
- Huntington’s disease
- Friedrich’s ataxia
- C9orf72
Links
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Talk Citation
Rubinsztein, D.C. (2020, June 30). Microsatellite and trinucleotide repeat expansion diseases [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 4, 2024, from https://doi.org/10.69645/PIIO2799.Export Citation (RIS)
Publication History
Financial Disclosures
- No conflicts of interest for this talk.
Other Talks in the Series: Introduction to Human Genetics and Genomics
Transcript
Please wait while the transcript is being prepared...
0:00
I'm David Rubinsztein.
I'm a professor of molecular neurogenetics at the University of Cambridge,
based in the Cambridge Institute for Medical Research,
and I'm also a UK Dementia Research Institute professor.
Today I'm going to tell you about microsatellites,
and trinucleotide repeat expansions diseases.
The focus of my talk is going to be on the genetics of these diseases,
and I'll talk very little about the functional biology of these conditions.
0:29
This slide provides an overview of
the different diseases I'm going to be talking about today.
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.
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.
But in a diseased chromosome,
you might have 40 successive copies of CAG trinucleotides in the gene.
What this slide shows is that these types of
mutations can occur in various parts of the gene.
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.
The other key point of the slide is to show that these diseases are
typically either neurological, neurodegenerative, or neuromuscular.
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.