Human Genetics Flashcards
What kind of mutations can occur in multicellular organisms ?
- somatic mutations
- germ-line mutations
What are the 2 kinds of alterations to the DNA nucleotide sequence ?
- point mutation
- chromosomal mutations
Define genetic heterogeneity
a single disorder, trait or pattern of traits caused by genetic facts in some cases and non-genetic factors in other
Describe a substitution mutation
- it exchanges one base for another
Describe transition substitutions
Transitions are base changes to the same type of base –> between A and G (purines) and between C and T (pryimidines)
Describe transversion substitutions
They’re base changes to a different type of base, so from a purine to a pyrimidine
Describe Insertion mutations
extra base pairs are inserted into a new place in the DNA
Describe deletion mutations
sections of DNA is lost or deleted
Describe Frameshift mutations
since the protein-coding DNA is divided into codons, insertions and deletions can alter the ORF
Describe rearrangement mutations
duplications, inversions and translocations
What is a single nucleotide polymorphism ?
SNP is a change in which a single case in the DNA differs from the usual base at that position
- key in genetic variation
What are some examples of loss of function mutations ?
- complete loss of the protein
- reduction of protein’s ability to work
What are some examples of gain of function mutations ?
- increase in the proteins function
- a protein that interferes with the wild type proteins function
- acquisition of a new function
What are the 2 common types of exceptions ?
- haploinsufficiency
- dominant negative or antimorphic
Define Haploinsufficiency mutations
one copy of the gene isn’t enough
Define Dominant negative/antimorphic mutations
the defective gene interferes with the function of the wild-type copy
What is a silent mutation ?
a point mutation which results in no change in amino acids in protein
What are the 4 types of chromosomal mutations ?
- deletions
- duplications
- inversions
- translocations
What are the benefits & costs of germ line mutations?
- provide genetic diversity for evolution
- usually produces an organism that does poorly in its environment
What are some sources of DNA damage ?
- mistakes in replications
- spontaneous
- environmental (radiation/carcinogens)
Describe spontaneous mutations
permanent changes caused by several mechanisms ;
- errors in replication that aren’t repaired
- imperfect meiosis
- nucleotides occasionally change their structure = tautomeric shift
- base loss
Describe Base Loss as a form of spontaneous damage
- sometimes bases just fall off
- phospodiester backbone is still intact
- purines are more sensitive than pyrimidines
- causes mutations that can lead to strand breaks
Describe Deamination as a form of spontaneous damage
- concerts cytosine to uracil
- altered base has different base paring rules - U pairs with A
What are induced mutations ?
permanent changes caused by some outside agent
- oxidation
- deamination
- radiation damage
Describe oxidative stress
- Reactive oxygen species = things that are/give rise to oxygen with an unpaid electron (free radical)
- ROS’s are produced by respiration & radiation
- ROS’s are removed by enzymes & reducing agents
How do ROS cause damage ?
- breaks bonds –> base loss, phosphodiester backbone
- single strand breaks and rarely double strand breaks
How does ionising radiation damage DNA?
- damage is usually a secondary consequence of ROS generated from the radiolysis of water
- Damages bases
- strand breaks
How does UV light radiation damage DNA?
- bases absorb energy (260nM)
- photoactive base causing damage to bases
- results in covalent bonds between adjacent bases
- distorts DNA which can block transcription, replication –> leads to mutation
Describe Adduct formation
- harmful chemicals carcinogens) adduct to DNA
- not always direct exposure, sometimes the carcinogen is a toxic product of cellular metabolism
- groups are big, blocking transcription, replication & interfering with base pairing
Define Intra-strand crosslinks
between adjacent nucleotides, like UV photoproducts
Define Inter-strand crosslinks
between nucleotides on opposite strands of double helix
- completley block transcription & replication
What 3 steps give rise to high-fidelity DNA synthesis ?
- 5’-3’ polymerisation
- 3’-5’ exonucleolytic proofreading
- strand-directed mismatch repair
Explain micro satellite instability
slippage of primer or template during replication causes expansion/contraction of microsatellite
