Week 1 - Genetic Change & Its Consequences Flashcards
What is a mutation and how are they categorised?
- genetic changes that can cause a disease
- they can be inherited by germline mutation or acquired by somatic mutation
- they can be silent or functional
- can be neutral, favourable, and non-favourable
What are chromosomes aberrations?
- chromosome defects that are either structural or numerical
structural: translocation, inversion, insertion, duplication, amplification, deletion
numerical: loss/gain of whole chromosome or its set
What is the effect of a nonsense mutation?
- it created a truncated protein, which is a protein shorter than its full-length version due to a premature stop codon
- this protein can interact with normal proteins
What types of mutations are there (specific to the change in the amino acid sequence)?
point mutation: change in a singular gene
frameshift: disrupting the triplet code
splicing: affecting splice sites (introns & exons)
regulatory: affecting the promoter or other regions causing an aberrant (unusual) expression
What are the effects of mutations in non-coding regions?
promoter: rate of gene transcription
regulatory region / operator site: gene regulation failure
UTR: disruption to mRNA translation / stability
splice sites: disrupted pre-RNA splicing
t/micro/long noncoding RNAs: dysfunctional gene regulation
What are the types of amino acid replacements?
conservative replacement: exchanged amino acids have similar properties and rarely cause protein dysfunction
radical (non-conservative): different properties causing pathogenic changes
What is haploinsufficiency?
- when one copy of the gene has been inactivated by a mutation
- the other copy has a reduced expressions so it is insufficient to fulfill its function
- OR it makes 50% of the product but it is not enough
What is transversion and transition mutation?
- transition is when a point mutation changes a purine nucleotide to another purine nucleotide or pyrimidine to another pyrimidine
- transversion is when the purine becomes a pyrimidine or vice versa
What is the rule for chromosome nomenclature?
- chromosome number
- short (p) / long arm (q)
- region
- band
decimal point - sub-band
How are cells prepared for karyotyping?
- cells are collected from either lymphocytes, skin, or amniocytes
- cultured
- arrested in metaphase using colchicine
- lysed with hypotonic saline
- mounted
- fixed
- stained with giemsa stain
- converted into ideograms for better visualisation
Why do dominant-negative mutations happen?
proteins often act as a part of a network by binding to each other and forming dimers/ multimers
How is BRCA1 and 2 an example of antagonistic pleiotropy?
- they increase cancer risk and tumour development, thus decreasing a person’s chance of survival but they also increase women’s fertility
- a positive and negative effect
What are the different types of centromere positions?
metacentric: in the middle
submetacentric: shifted away from the middle
acrocentric: near the end - short arms form satellites
telocentric (only in mice): at the very end
What is pleiotropy?
when one gene influences two or more phenotypic traits that can be unrelated
What is haplosufficiency?
when the one working copy is sufficient for the gene to function so the normal phenotype is maintained
What is a dominant-negative mutation?
- when the mutated gene product interacts with the normal wild-type gene product within the same cell
- it can interact in the same way as the wild-type or block aspects of its function
What is a loss of function mutation?
- mutations that reduce or prevent gene function
- can be a complete loss or a dysfunctional protein
