DNA - Pathogenic Variants Flashcards
(18 cards)
Why is a polyA tail added to mRNA during splicing?
To prevent degradation of the mRNA strand.
What is exon shuffling? Example of where it might be used?
The process by which new proteins can be made from the same gene by alternative splicing.
Immune system.
Why is a mutation that leads to a STOP codon significant?
Produces truncated mRNA. Truncated mRNA often degrades so the protein either isn’t made at all or an incomplete, faulty protein is made. This causes disease.
What are some types of variant?
- duplications / deletions
- regulatory sequence variants
- splice site variants
- premature stop codon (nonsense)
- substitution of amino acid (mis-sense)
- expansion of tri-nucleotide repeats
What is the result of a splice-site variant?
Intron not accurately removed so the intron is translated into the protein / the exon is not translated into the protein.
What is nonsense mediated decay?
The process by which the cell detects and degrades mRNA that contains premature STOP codons.
What are some indicators of a pathogenic variant?
- the variant changes an amino acid which is conserved through evolution
- disrupts active site or splice site
- not present in a large number of normal individuals
- seen previously in individuals with the same condition
- functional studies show an effect on protein function
What does anticipation mean?
The trinucleotide repeat expands when transmitted to the next generation - symptoms of the disease develop earlier and are more severe.
What is allelic heterogeneity? Example of a disease with allelic heterogeneity?
There are lots of different variants in one gene.
Cystic fibrosis.
What is locus heterogeneity? Example of a disease with locus heterogeneity?
When variants in different genes lead to the same clinical condition.
Hypertrophic cardiomyopathy.
What is a loss-of-function variant?
When only one allele is functioning.
Might cause haplo-insufficiency as only half the amount of protein is produced, so if pathway relies on amount of protein this causes problems.
What is a gain-of-function variant?
More copies of the gene (alleles) are present. This leads to increased protein activity, e.g. amyloidosis.
What is a dominant-negative variant?
Protein from variant allele interferes with protein from the normal allele.
What is predictive testing?
Testing healthy at-risk family members for a variant found in a patient.
What is carrier testing and when is it particularly important?
Testing if an individual carries an allele for an autosomal recessive / X linked disease.
Important for reproductive decision making.
What is pre-natal genetic testing?
- tests for severe, life-limiting conditions where an increased risk has been identified
- chorionic villus sampling / amniocentesis (carries risk of miscarriage)
- non-invasive tests becoming available (mostly privately) such as maternal blood tests
What is PGD?
Pre-implantation Genetic Diagnosis (IVF)
- one cell from the developing embryo is removed for genetic testing prior to implantation
What is susceptibility testing?
An emerging genetic test to identify increased or decreased risk of developing a multi-factorial condition.
