Lecture 13- Mutations Flashcards
Define:
A) mutation
B) mutagenesis
A) a change of the of he nucleotide sequence
B) the process of mutation generation
Difference in mutation in somatic cells and germ line cells?
- mutations can be passed on if there are DNA changes in the egg and sperm cells, not in somatic cells
Causes of mutation
EXOGENOUS:
- ionising radiations/particles
- free radicals
- mutagenic chemicals
- anti-cancer agents
SPONTANEOUS EVENTS!!
ENDOGENOUS:
- DNA replication defects
- transposable elements (transposons)
What is spontaneous deamination and why does it lead to mutation?
- the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process
What are transposons?
- a specific DNA sequence that can change position within a genome
- they transpose as a discrete unit to random sites
- may insertionally inactivate genes or change gene expression
- always contained within other DNA molecule
How do transposons work?
They can insert themselves into genes via transposition and can then lead to the inactivation of genes or changing gene expression
Is mutation always a bad thing?
- it may or may not cause a phenotypic change
- can be good or bad
- its a source of genetic variation and hence is a driving force of evolution
- but it may cause disease
What are the 3 types of single nucleotide DNA mutations ?
- Base substitutions
- Base insertion
- Base deletion
A) What are the two types of single base substitutions?
B) What are the different effects of these?
A) 1. Transition: change to same base- purine substituted with another purine or pyrimidine substituted with another pyrimidine
- Transversion: change to a different type of base: purine to pyrimidine and vise versa
B) 1. Silent mutation: when DNA change does not alter the AA sequence of th polypeptide (due to degenerate code and usually due to 3rd codon change)
- Missense mutation: when DNA change alters a single AA in the chain i.e. sickle cell anaemia
- Nonsense mutation: results in a stop codon truncating translation, usually leads to a non functional protein
What is a frameshift mutation and what are the two types of single base changes that cause this?
Frameshift mutation: caused by the addition or deletion of a base resulting in the translation of the genetic code in a different reading frame from the position of mutation to the end of the gene
- Insertion: base is inserted into replicating DNA: frameshift (+1) mutation
- Deletion: nucleotide excised from replicating DNA: frameshift (-1) mutation
Outline how sickle cell anaemia is caused by a mutation
Sickle cell anemia: abnormality in the haemoglobin in RBC
- Autosomal recessive inheritance
Caused by Base subsitution mutation, one AA is changed (the 6th aa changed from glu to Val)
- missense mutation
- mutation in codon 7 of HBB
Which single nucleotide changes result in the following:
A) change gene product (polypeptide or RNA)
B) Change amount of gene product
C) change polypeptide length
D) do not have an effect
A) missense mutation/non-synonymous mutation
B) mutations affecting regulatory sequences (alter promoter activity, alter translation initiation at AUG, prevent mRNA splicing)
C) frameshift mutation or mutation of stop codon or nonsense mutation
D) silent or neutral mutation
A) What are chromosome mutations?
B) What are the types of structural chromosomal mutations?
Mutations/abnormalities
A) Change in portion of chromosomal DNA
B)
- Deletions: portion of chromosome is deleted
- Duplications: portion of chromosome duplicated, extra genetic material
- Inversions: portion of chromosome broken off and flips and becomes attached to the rest but upside down
- Substitutions/insertions
- Translocations; portion of chromosome breaks off and attaches to a different chromosome
What are some numerical abnormalities of chromosomes?
- Polyploidy: gain of haploid set of chromosomes (3n=69)
- Aneuploidy: loss and gain of whole chromosomes caused by non-disjunction in meiosis
- Trisomies: more than 2 chromosome s in a pair e.g. Down syndrome
- Monosomies: a chromosome missing from a pair e.g. Turner syndrome - Mosaicism: presence of two or more cell lines in an individual (throughout the body or tissue), caused by non-disjunction in mitosis
A) What is cytogenetic testing ?
B) what are the types?
A) It is the examination of chromosomes to identify structural abnormalities
B) - Cytogenetic analysis: karyotyping (examines dividing cells)
- Fluorescent in situ hybridisation (FISH): paints chromosomes or portions of chromosomes with fluorescent molecules to identify mutations
- Microarray hybridisation
- DNA sequencing
