5. GENE MUTATION Flashcards
What are types of gene mutations?
Deletions, insertions, inversions, translocations, and other changes affecting one base pair to thousands.
How can large differences in DNA sequence affect proteins?
They likely have significant effects on protein sequence
What is the effect range of point mutations on protein sequences?
They can cause various effects; changing one or a few base pairs may or may not alter the amino acid
Which sequencing method is used to analyze point mutations and their context?
Sequencing, which also provides the context of neighboring bases
What additional information can some sequencing methods provide?
The percentage of variant alleles relative to a reference sequence
What are limitations of different sequencing technologies?
Difficulty with detecting structural chromosomal abnormalities and copy-number variations
What is required to confirm germline variants detected by NGS in genetic testing?
Confirmation by Sanger sequencing or other methods
How are phenotypic changes in protein structure predicted?
By analyzing the nucleotide sequence
Why are standard biochemical, cytogenetic, and molecular methods still important?
They are used for analyzing frequently occurring variants via simple and inexpensive tests.
Why might DNA sequence changes not alter the amino acid sequence?
Due to the redundancy in codons for most amino acids.
What are the three outcomes of nucleotide substitutions?
Silent (no amino acid change), conservative (similar properties), or nonconservative (biochemically different amino acid).
A mutation that replaces an amino acid codon with a stop codon, causing premature protein termination
nonsense mutation
What percentage of disease-related gene lesions are nonsense mutations?
About 11%
What results from insertion or deletion of nucleotides not in multiples of three?
A frameshift mutation, altering the triplet reading frame
Why do frameshifts often lead to premature stop codons?
The genetic code structure often brings a stop codon sooner in the out-of-frame sequence
Where do nonconservative, nonsense, and frameshift mutations cause different phenotypes
Depending on their location along the protein sequence
How does the mutation location affect the mutation’s impact?
Mutations at the 3’ end of coding regions often have minor effects, while those at the 5’ end may cause major alterations
Why might finding a change in DNA sequence not always indicate an altered phenotype?
Point mutations must be screened to identify silent, conservative, or nonconservative effects.
are specific DNA changes often inherited with disease phenotypes and are mapped near disease genes
single-nucleotide polymorphisms (SNPs)
Give an example of a gene with multiple disease-associated mutations
The cystic fibrosis transmembrane regulator (CFTR) gene has over 600 such mutations.
What challenge exists in detecting mutations in large genes
Screening across thousands of base pairs to identify a single altered nucleotide
What methods analyze the actual protein or amino acid alteration
Biochemical methods detect direct protein changes, especially in metabolic defects
How do immunoassays work in detecting various analytes?
They use antibodies to capture and detect target molecules in biological fluids
What is the principle of enzyme-linked immunosorbent assays (ELISAs)?
Use of capture and detection antibodies with a substrate to produce signals like color or light