DNA Mutations Flashcards
What is the benefit of alternative splicing?
Different proteins can be made from the same gene
What is deletion?
Removal of a base, disrupts the protein
What is non-sense variant?
Change codon to stop
Out of frame deletion produces a stop codon either at deletion site or further along
RNA detaches from the ribosome and is eliminated
What is mis-sense variant?
Single base substitution
Changes the type of amino acid in the protein
May or may not be pathogenic
May be a polymorphism of no functional significance
What is a pathogenic variant?
The variant is responsible for causing disease
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
What is the difference between dominant and recessive variants?
Dominant variants manifest the disease phenotype in the heterozygous state i.e. the condition occurs if there is one variant and one normal allele
Recessive variants only manifest the disease in the homozygous state i.e. there have to be variants in both alleles. The majority of pathogenic variants are recessive.
Mechanisms of dominance: Loss of function variants
–Only one allele functioning. Most loss of function variants are recessive
–If a pathway is very sensitive to the amount of gene product so that if only half is produced it cannot function this will cause a problem
–Haplo-insufficiency
Mechanisms of dominance: 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. a variant may occur at the recognition site for protein degradation leading to an accumulation of undegraded protein within the cell
Mechanisms of dominance: Dominant-negative variants
–Where the protein from the variant allele interferes with the protein from the normal allele.
–E.g. a dimer where one variant and one normal allele would result in only 25% normal dimers
What Clinical context do genetic tests depend on?
•Diagnostic
•Predictive
•Carrier
•Pre-natal
•Preimplantation genetic diagnosis
•Screening
•Susceptibility
What is a diagnostic test?
•Patient has signs and symptoms suggesting a particular diagnosis
•A molecular genetic test will confirm a diagnosis
•In this context a genetic test is being used to confirm a clinical diagnosis.
•Issues informed consent
What is predictive testing?
•Testing health at-risk family members for a previously identified familial variant – often dominant
•HD No intervention
•BRCA1/2 some intervention
What is carrier testing?
•Autosomal recessive and X-linked disorder
•Testing an individual in isolation not particularly helpful – couple testing
•Reproductive decision making
