DNA mutations Flashcards
types if variant
duplications of genes or parts of them
deletions
variants within regulatory sequence
splice site variants
premature stop codon-nonsense variant
mis-sense variant
expansion of trinucleotide repeats
deletions
out of frame deletion clearly disrupts the protein
in frame deletion
out of frame deletion + example
one letter being deleted
absence of dystrophin in DMD
in frame deletion + example
deletion of 1 whole codon
milder Becker Muscular dystrophy
splice site variant
affects accurate removal of an intron
non-sense variant
change codon to stop
out of frame deletion produces stop codon at deletion site or further along
RNA detaches from ribosome and is eliminated
nonsense mediated decay
mis-sense variant
single base substitution
changes type of amino acid in protein
may or may not be pathogenic
may be a polymorphism of no functional significance
pathogenic variant or polymorphism?
changes amino acid conserved through evolution
disrupts active site or splice site
not common
effect on protein function
expansion of a tri-nucleotide repeat
huntington’s disease CAG
myotonic dystrophy CTG
fragile X CGG
heterogeneity
one gene one variant one disease
huntingtons
allelic heterogeneity
lots of different variants in one gene
locus hetergeneity
variants in different genes give same clinical condition
hypertrophic cardiomyopathy
different variants in same gene can give rise to different conditions - genotype/phenotype correlations
dominant variants
manifest disease phenotype in heterozygous state
one variant and one normal allele
recessive variants
homozygous state
variants in both alleles
majority of pathogenic variants
loss of function variants
only one allele functioning. most recessive
haplo-insufficiency
gain of function variants
increased gene dosage e.g. PMP22 duplication on 1 allele in hereditary motor and sensory neuropathy type 1A
increased protein activity e.g. variant occurs at recognition site for protein degradation leading to accumulation of undegraded protein within cell
dominant-negative variants
protein from variant allele interferes with protein from normal allele
genetic test clinical contexts
diagnostic predictive carrier prenatal preimplantation genetic diagnosis screening susceptibility
diagnostic test
patient has signs and symptoms suggesting a particular diagnosis
molecular genetic test will confirm a diagnosis
predictive testing
testing at risk family members for a previously identified familial variant - often dominant
Huntingtons no intervention
BRCA1/2 some intervention
carrier testing
autosomal recessive and X-linked disorder
testing individual not helpful - couple testing
reproductive decision making
pre-natal test
increased risk of specific condition affecting the fetus
chorionic villous sample or amniocentesis
chromosomal or DNA if specific familial variant has been identified
genetic screening
target population, not high risk families
susceptibility testing
increased or decreased risk for a multifactorial condition
issue only just emerging
