Human Genetics

Question 1

What kind of mutations can occur in multicellular organisms ?

Answer 1

• somatic mutations
• germ-line mutations

Question 2

What are the 2 kinds of alterations to the DNA nucleotide sequence ?

Answer 2

• point mutation
• chromosomal mutations

Question 3

Define genetic heterogeneity

Answer 3

a single disorder, trait or pattern of traits caused by genetic facts in some cases and non-genetic factors in other

Question 4

Describe a substitution mutation

Answer 4

• it exchanges one base for another

Question 5

Describe transition substitutions

Answer 5

Transitions are base changes to the same type of base –> between A and G (purines) and between C and T (pryimidines)

Question 6

Describe transversion substitutions

Answer 6

They’re base changes to a different type of base, so from a purine to a pyrimidine

Question 7

Describe Insertion mutations

Answer 7

extra base pairs are inserted into a new place in the DNA

Question 8

Describe deletion mutations

Answer 8

sections of DNA is lost or deleted

Question 9

Describe Frameshift mutations

Answer 9

since the protein-coding DNA is divided into codons, insertions and deletions can alter the ORF

Question 10

Describe rearrangement mutations

Answer 10

duplications, inversions and translocations

Question 11

What is a single nucleotide polymorphism ?

Answer 11

SNP is a change in which a single case in the DNA differs from the usual base at that position
- key in genetic variation

Question 12

What are some examples of loss of function mutations ?

Answer 12

• complete loss of the protein
• reduction of protein’s ability to work

Question 13

What are some examples of gain of function mutations ?

Answer 13

• increase in the proteins function
• a protein that interferes with the wild type proteins function
• acquisition of a new function

Question 14

What are the 2 common types of exceptions ?

Answer 14

• haploinsufficiency
• dominant negative or antimorphic

Question 15

Define Haploinsufficiency mutations

Answer 15

one copy of the gene isn’t enough

Question 16

Define Dominant negative/antimorphic mutations

Answer 16

the defective gene interferes with the function of the wild-type copy

Question 17

What is a silent mutation ?

Answer 17

a point mutation which results in no change in amino acids in protein

Question 18

What are the 4 types of chromosomal mutations ?

Answer 18

1. deletions
2. duplications
3. inversions
4. translocations

Question 19

What are the benefits & costs of germ line mutations?

Answer 19

• provide genetic diversity for evolution
• usually produces an organism that does poorly in its environment

Question 20

What are some sources of DNA damage ?

Answer 20

• mistakes in replications
• spontaneous
• environmental (radiation/carcinogens)

Question 21

Describe spontaneous mutations

Answer 21

permanent changes caused by several mechanisms ;
- errors in replication that aren’t repaired
- imperfect meiosis
- nucleotides occasionally change their structure = tautomeric shift
- base loss

Question 22

Describe Base Loss as a form of spontaneous damage

Answer 22

• sometimes bases just fall off
• phospodiester backbone is still intact
• purines are more sensitive than pyrimidines
• causes mutations that can lead to strand breaks

Question 23

Describe Deamination as a form of spontaneous damage

Answer 23

• concerts cytosine to uracil
• altered base has different base paring rules - U pairs with A

Question 24

What are induced mutations ?

Answer 24

permanent changes caused by some outside agent
- oxidation
- deamination
- radiation damage

Question 25

Describe oxidative stress

Answer 25

• 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

Question 26

How do ROS cause damage ?

Answer 26

• breaks bonds –> base loss, phosphodiester backbone
• single strand breaks and rarely double strand breaks

Question 27

How does ionising radiation damage DNA?

Answer 27

• damage is usually a secondary consequence of ROS generated from the radiolysis of water
• Damages bases
• strand breaks

Question 28

How does UV light radiation damage DNA?

Answer 28

• 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

Question 29

Describe Adduct formation

Answer 29

• 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

Question 31

Define Intra-strand crosslinks

Answer 31

between adjacent nucleotides, like UV photoproducts

Question 32

Define Inter-strand crosslinks

Answer 32

between nucleotides on opposite strands of double helix
- completley block transcription & replication

Question 33

What 3 steps give rise to high-fidelity DNA synthesis ?

Answer 33

1. 5’-3’ polymerisation
2. 3’-5’ exonucleolytic proofreading
3. strand-directed mismatch repair

Question 34

Explain micro satellite instability

Answer 34

slippage of primer or template during replication causes expansion/contraction of microsatellite