DNA pathogenic variants Flashcards
variant alleles
pathogenic variant
polymorphism
benign variation
splicing
introns spliced out
enhancer and promoter are also non-coding
if there is alternative splicing different proteins can be made from the same gene
exon shuffling allows new proteins to be made e.g. the immune system
stop codon
mark end of function of gene, if a mutation causes a stop codon earlier in sequence it can cause genetic disease
types of variant
duplications
deletions
variations within the regulatory sequence
splice site variants
introduce premature stop codon - nonsense variant
replace one amino acid in protein with another - mis-sense variant
expansion of trinucleotide repeats
anticipation
repeat gets bigger when transmitted to the next generation and so symptoms develop earlier and are more severe
heterogeneity
one gene one variant one disease e.g. huntingtons
allelic heterogeneity
lots of different variants in one gene e.g. cystic fibrosis
locus heterogeneity
variants in different genes give the same clinical condition e.g. hypertonic cardiomyopathy
loss-of-function variants (mechanisms of defence)
only one allele functioning
gain-of-function variants (mechanisms of defence)
increased gene dosage, increased protein activity
dominant-negative variants (mechanisms of defence)
where the protein from the variant allele interferes with the protein from the normal allele
diagnostic test
patient has signs and symptoms, molecular genetic test to confirm clinical diagnosis
predictive testing
health at-risk family members for a previously identified familial variant - often dominant
carrier testing
autosomal recessive and x-linked disorder, testing an individual in isolation not particularly helpful - couple testing, reproductive decision making
