Errors Involving DNA Flashcards
What are oncogenes?
Genes that increase growth, promotes survival and inhibit apoptosis
Why might oncogenes have an increase in activity?
Due to mutation (either in the gene itself, in other involved signalling proteins or in the transcription factor binding region).
What are tumour suppressing genes?
Genes that inhibit proliferation, reduce growth or promote apoptosis
What is the p53 gene?
A tumour suppressing gene that is commonly mutated
What is slippage in DNA replication?
Where a newly synthesised nucleotide/strand can slip out and so there are extra nucleotides on the strand. Or nucleotides can slip out on the template strand, shortening the DNA strand.
What is mis-match pairing?
When DNA polymerase inserts the wrong nucleotide
How can a mismatch be easily repaired?
There can be a base excision repair from the exonuclease domain of the DNA polymerase.
What results from an increase of p53 activity?
Tumours
What is DNA replication stress?
Inefficient replication that leads to the replication fork slowing, stalling or breaking
What happens when the replication fork meets a single strand break?
A double strand break occurs
What disease results from a trinucleotide repeat?
Huntingtons
What is dysplasia?
Features of abnormal cell growth
Errors in what 4 areas lead to genomic instability?
- Errors in oncogenes
- Errors in tumour suppressing genes
- Errors in chromosome structure
- Errors in chromosome number
Increasing the activity of which genes results in dysplasia
Oncogenes
What is mismatch repair?
When DNA polymerase finds a mistake and so the exonuclease domain cuts out the mistake for polymerase to fix
Outline nucleotide excision repair
A stretch of damaged DNA is removed by endonuclease and replaced by DNA polymerase and joined together by DNA ligase, using a variety of proteins which are produced in the genes controlling this repair
What does UV light do to cells?
It initiates a reaction between 2 thymine molecule to form a pyrimidine dimer.
Why can some DNA synthesis inhibitors be used as antibiotics?
They may only inhibit bacterial DNA synthesis not human
What is non-homologous end joining used to repair
Double stranded breaks
Outline non-homologous end joining
The ends are directly lighted. This is done by proteins binding onto the ends of the breaks, which then recruit other proteins which removed damaged strands and then DNA ligase brings the strands together
What are chromosomal translocations?
When part of a chromosome attaches to another. It can be balanced or unbalanced
What is chromosomal inversion?
When a segment of DNA is reversed end to end.
What type of disease can be caused by translocations
Leukaemia
What is a mutation
An alteration in a gene or chromosome
What is a bulky addict
When chemicals bind to areas of DNA and prevent it replicating
When do mutations occur
When DNA repair mechanisms are defective
State exogenous sources of mutation
Ionising radiation, free radical, mutagenic chemicals
What are free radicals
Molecules with an extra electron
State endogenous sources of mutation
DNA replication defects and transposable elements
What are transposable elements
When DNA has no fixed position and move around the genome
What happens when a transposable element is inserted into a gene
It deactivates the gene
What is a mircomitation
Mutation involving one or few nucleotides
What is a macromutation
Mutation on chromosomes
What types of micromutations are there?
Deletions, insertions, substitutions
What types of macromutations are there
Deletion, duplication, inversion, substitution and translocation
What do deletions and insertions result in
Frameshift
What are missense mutations
Mutations resulting in a change in amino acid
What are silent mutations
Genes that give no change in amino acid
What is a nonsense mutation
Mutation resulting in an early stop codon
What types of mutations affect the amount of gene product
Mutations affecting translation or transcription
How may mutations affecting splicing affect gene product
Mutations at the end of intron mean splicing sequences change so exams aren’t removed. The change in length makes non functional proteins
How does nitrous acid mutate DNA
It changes cytosine to uracil
What is a transition mutation
When a purine is changed to a purine or a pyrimidine changed to a pyrimidine
What is a transversion mutation
When a purine is changed to a pyrimidine
What cells do germ line mutations effect
Sperm and egg
Why do rna errors occur often
RNA Polymerase don’t proofread
Why are mutations in rna often not harmful
RNA degrades quickly not passed on and the cell makes multiple copies o DNA
What organs are badly affected by mutations in mitochondria
Organs requiring lots of energy e.g heart, brain and muscle
From whom do you inherit your mitochondria from
Your mother
What results in aneuploidy
Nondisjunction
What is anaphase lag
When chromosomes aren’t separated properly during anaphase
Are are monosomy cells not usually found
As they are fatal and result in death
What are primordial germ cells
Cells which develop into sperm and ovum
What is the significance of large amounts of division of germ cells
Lots of chance for mutation
Why does mutation rate of gametes increase with age
More exposure to mutagens/radiation
What is teratogensis
The process by which mutations are produced in an embryo
What do recessive mutations cause
Loss of function
What do dominant mutations occur
Increased function
What is cytogenetics
Study and analysis of chromosomes
What constitutional Abnormalities result in referral for cytogenetic analysis
Prenatal diagnosis, birth defect, infertility and reoccurring fetal loss
What acquired Abnormalities result in referral for cytogenetic analysis
Leukaemia, tumours and specific translocations
What 2 types of prenatal diagnosis methods are there
Chorionic villus and amnioticentesis
What is chorionic villus
Inserting a needle to collect some chorionic fluid which surrounds the placenta using ultrasound
What is amniocentesis
Collecting amniotic fluid using a needle and ultrasound guidance
What is polyploidy
Gain of a whole haploid set of chromosomes
What causes polyploidy
Fertilisation of an egg by more than one sperm
What are the causes aneuploidy
Nondisjunction
What is mosicaism
2 cell populations in an individual
What is Down’s syndrome
Trisomy 21
What symptoms are associated with Down’s syndrome
Intellectual disability. Heart defects, increased incidents of leukaemia and Alzheimer’s
What is the syndrome caused by trisomy 18
Edwards syndrome
What symptoms are associated with Edwards syndrome
Small lower jaw, low set ears, rocker bottom feet and overlapping fingers
What is Patau syndrome
Trisomy 13
What is single X chromosome inactivation
Where only 1 X chromosome is ever active in a human cell
Why is single XChromosome a problem
2 X chromosomes are required to activate genes
What is the name of the syndrome when you only have 1 X chromosome
Turner syndrome
What symptoms are associated with Turner syndrome
Puffy feet,, redundant skin at the back of the neck
What are balanced translocations
Where there is an even exchange of genetic information with no loss of gain
What are unbalanced translocations
Where there is a loss or gain of genetic information
Can microarray detect both balanced and unbalanced translocations
No only unbalanced
What types of segregation result in balanced translocations
Alternate
What types of segregation results in unbalanced translocations
Adjacent, and nondisjunction
What are Robertsonian translocations
When the q arms of 2 Acrocentric chromosomes fuse together
What diagram is used to assess segregation imbalance
Pachytene diagram
What are terminal deletions/duplications
Ones that occur towards the ends of a chromosome
What are interstitial deletions/deletions
Ones that occur in the chromosome arm
What is uniparental disomy
Presence of homologous chromosomes from one parent
What is the significance of uniparental disomy
It affects imprinting (differential expression of genes depending on parental origin of chromosome)
How is uniparental disomy caused
Trisomy rescue, mitotic error
Why might women with balanced translocations have repeated miscarriages
As the separation of their chromosomes result in unbalanced translocations which aren’t viable for life
Are gain of function mutations more likely to be dominant or recessive
Dominant
What genes are mutated to give oncogenes
Proto oncogenes
What is bulky adduct
When chemicals are added to DNA which stop it replicated
How does nitrous acid mutate DNA
Changes cytosine to uracil by replacing an NH2 group
