DNA mutations and genetic testing Flashcards
(48 cards)
What is a polymorphism
the presence of 2 or more variant forms of specific DNA sequence that occur among different individuals or populations - most common type is single nucleotide polymorphism (SNP) but they can be larger involving longer stretches of DNA. Usually benign and helps to maintain variation in a population
what are the stop codons
UAA, UGA, UAG
what is a mis-sense variant
A single base substitution which changes the type of amino acid in the protein, can be both pathogenic and non-pathogenic. It could also be a polymorphism of no functional significance
what are the different types of variation
- Duplications (of whole or parts of a gene)
- ## Deletions (of whole genes or some exons)
what is an out of frame mutation
the removal or addition of one or more nucleotide which severely disrupts the production of the protein as the shift of bases causes different amino acids to be coded for e.g. duchenne muscular dystrophy
ATC GT(C) TTA CGC
to
ATC GTT TAC GCG
what is an in-frame mutation
A deletion where the reading frame of the gene is preserved - 3 nucleotides (1 codon) are removed - only 1 amino acid is no longer made and the other codons are unaffected
ATC (GTC) TTA CGC
to
ATC TTA CGC TGC
what is an exon
Segment of a DNA or RNA molecule containing information coding for a protein or peptide sequene
What is an intron
A segment of a DNA or RNA molecule which doesn’t code for proteins and interrupts the sequence of genes
what is a splice-site variant
It affects the accurate removal of an intron to make mature RNA containing only exons, so instead the intron is translated into the protein rather than being removed. This can also cause the loss of exons (or part of an exon) so they aren’t incorporated into the protein
where is a splice site
at the boundary of an exon and an intron
what is a non-sense variation
An out of frame deletion produces a stop codon at a deletion site or further along - causes the protein construction to be stopped prematurely - non-sense mediated decay
how do you tell between a pathogenic variant or a polymorphism
- changes an amino acid which had been conserved through evolution (pathogenic)
- Disrupts the active site or splice site (pathogenic)
- Not seen in a large number of normal individuals
seen previously in individuals with the same condition and shown to segregate with the disease (pathogenic) - functional studies showing an effect on protein function (Pathogenic)
Whats is a tri-nucleotide repeat (TNR) expansion
tri-nucleotide repeat (TNR) expansion is when the number of triplets (e.g. huntingtons = CAG) present in a mutated gene is greater than the number found in a normal gene, the number of repeats in the diseased gene increases as it is inherited so in the next generation the symptoms develop earlier and are more severe (anticipation)
what is anticipation
repeat gets bigger when transmitted to the next generation and so symptoms develop earlier and are more severe
what is allelic heterogeneity
lots of different variants in one gene e.g. cystic fibrosis
what is locus heterogeneity
variants in different genes give the same clinical condition e.g. hypertrophic cardiomyopathy
In which state does the dominant variant manifest the disease phenotype
heterozygous state - i.e. the condition occurs if there is one variant and one normal gene
In which state does the recessive variant manifest the disease phenotype
homozygous state - i.e. there has to be variants in both alleles for it to be expressed, the majority of pathogenic variants are recessive
what is a loss-of-function variant
Only 1 allele is functioning - most loss-of-function variants are recessive. If a pathway in the body is sensitive to the amount of gene product produced and only half is produced then it will not be able to function and this will cause a problem
what is haplo-insufficiency
The situation that occurs when one copy of a gene is inactivated or deleted and the remaining functional copy of the gene is not adequate to produce the needed gene product to preserve normal function.
what are gain of function variants
A type of mutation in which the altered gene product possesses a new molecular function or a new pattern of gene expression. Gain-of-function mutations are almost always Dominant - they can cause a new trait to appear in inappropriate tissues or at inappropriate times in development. A variant may occur at the recognition site for protein degradation leading to an accumulation of undegraded protein within the cell
what is a dominant-negative variant
where the protein from the variant allele interferes with the protein from the normal allele
what are the different clinical contexts for genetic testing
- Diagnostic
- Predictive (plan for the future if going to be affected)
- carrier (helps with decisions about bearing children)
- pre-natal (to check the baby is affected or not - abortion?)
- Pre-implantation genetic diagnosis (IVF)
- Screening
- susceptibility
why would a patient get a diagnostic test
if they are showing signs and symptoms suggesting a diagnosis and so they have a test to confirm a clinical diagnosis. the issues involved are informed consent as other people may be affected by the results
