mutations

Question 1

what is a gene/point mutation?

Answer 1

a gene/point mutation involves chemical changes that affect the DNA sequence of just one gene. they involve changes at specific sites in a gene, resulting in a change in one or a few bases in the DNA sequence

Question 2

what are the 2 basic types of changes to a gene in gene/point mutations?

Answer 2

1. nucleotide substitutions - the replacement of one nucleotide pair with another
2. nucleotide insertions or deletions - the addition or deletion of one or more nucleotide pair

Question 3

what are the 4 types of nucleotide substitutions?

Answer 3

1. missense mutation
2. nonsense mutation
3. silent mutation
4. neutral mutation

Question 4

what is missense mutation and its effects?

Answer 4

missense mutation is a nucleotide substitution in a DNA sequence that changes the mRNA codon, resulting in the translation of a different amino acid
change in a.a. sequence of polypeptide = change in specific 3D conformation of protein = function of protein is altered
eg: sickle cell anaemia

Question 5

what is nonsense mutation and its effects?

Answer 5

nonsense mutation is a nucleotide substitution in a DNA sequence that changes the codon for an amino acid into a stop codon
a.a. becomes stop codon = premature termination of translation = resulting polypeptide is shorter/truncated than normal = change in 3D conformation = function of protein is altered
nearly all nonsense mutations result in non-functional proteins

Question 6

what is silent mutation and its effects?

Answer 6

silent mutation is a nucleotide substitution in a DNA sequence that changes the mRNA codon, but the same amino acid is inserted into the polypeptide because of the degeneracy of the genetic code
same a.a. inserted = a.a. sequence of polypeptide unchanged = no change in 3D conformation of protein = function of protein is not altered

Question 7

what is neutral mutation and its effects?

Answer 7

neutral mutation is a nucleotide substitution in a DNA sequence that changes the mRNA codon, but the resulting substituted amino acid produces no detectable change in the function of the protein translated
a.a. sequence of polypeptide changed but no change in overall 3D conformation of protein = function of protein is not altered
this could arise from
- a.a. substituted has similar physical & chemical properties as the original
- a.a. residue of a.a. substituted is non-essential to the protein’s structure and function

Question 8

what are the 2 types of nucleotide insertions & deletions?

Answer 8

1. addition/deletion of nucleotides in multiples of 3
2. addition/deletion of nucleotide NOT in multiples of 3

Question 9

why are nucleotide insertions & deletions (not in multiples of 3) bad?

Answer 9

• resulting mRNA is read as a series of non-overlapping codons, an insertion or deletion of nucleotides not in multiples of 3 will result in a frameshift mutation
• all nucleotides downstream of the insertion/deletion site will be improperly grouped into codons, resulting in extensive missense
• frameshift may also cause a new, premature stop codon to be generated (nonsense mutation) OR result in a read-through of the normal stop codon, resulting in polypeptdes of altered lengths.
• frameshift mutations usually result in non-functional proteins

SINGLE BASE deletion or insertion mutations WILL lead to frameshift mutations.

Question 10

what is the effect of insertion mutation in multiples of 3?

Answer 10

insertion of nucleotides in multiples of 3 does not lead to a frameshift mutation, but the a.a. sequence of the polypeptide chain will contain additional a.a., which may change 3D conformation of the protein and the function of the protein may also change

Question 11

how is sickle cell anaemia manifested?

Answer 11

• the substitution of a thymine for an adenine at one position of the Hb gene results in a missense mutation
• the 6th a.a. residue in the polypeptide is changed from a hydrophilic glutamate to a hydrophobic valine
• creates a hydrophobic spot on the outside of the Hb protein that sticks to the hydrophobic region of an adjacent Hb protein’s beta chain
• mutant Hb subunits stick to each other when oxygen conc is low, esp in capillaries & veins
• aggregated proteins form fibre like structures within RBCs
• only at high oxygen conc, haemoglobin resumes its globular structure

Question 12

what are the physiological effects of sickle cell anaemia?

Answer 12

• fibre-like structures cause RBCs to lose their normal morphology and become sickle-shaped. sickled cells are less able to move through capillaries and can block blood flow, resulting in severe pain and cell death of the surrounding tissue due to shortage of oxygen
• sickled RBCs are fragile and easily destroyed, further decreasing the oxygen carrying capacity of blood

Question 13

what are the 2 types of mutations?

Answer 13

spontaneous mutations and induced mutations

Question 14

what are spontaneous mutations?

Answer 14

spontaneous mutations are mutations that occur naturally, without the use of chemical or physical mutagenic agents.
they may result from errors that occur during DNA replication, recombination or repair.

Question 15

how can spontaneous mutations arise from DNA replication & repair?

Answer 15

mistakes: DNA polymerase may insert the wrong/too many/too few nucleotide into the DNA sequence
attempts to correct: some mistakes are corrected immediately during replication during proofreading, some corrected after replication during mismatch repair.
replication errors may fail to be recognised by repair enzymes: altered nucleotide sequences are then passed down from 1 cellular generation to the next

during mismatch repair, incorrectly paired nucleotides cause deformities in the secondary structure of the final DNA molecule. enzymes recognise & fix these deformities by removing the incorrectly paired nucleotide and replacing it with the correct nucleotide

Question 16

how can spontaneous mutations arise from DNA slippage?

Answer 16

• daughter/parental DNA slips during DNA replication and folds back
• mispairing between the daughter DNA strand and parental DNA strand
• parts of the DNA which are folded back are copied more than once. if copied segments correspond to a gene, it results in gene duplication

Question 17

what are induced mutations?

Answer 17

induced mutations are the result of deliberate application of mutagens that increase mutation rates

Question 18

what are common physical & chemical mutagens and their effects on DNA?

Answer 18

physical mutagens:
- x-rays - produce double-stranded breaks leading to chromosomal rearrangements & deletions
- UV rays - lead to covalent attachment between adjacent pyrimidines or base pair substitutions, insertions and deletion. DNA replication & transcription are blocked

chemical mutagens:
- base analogues - are molecular structures that are similar to DNA bases, and produce base substitutions by being incorporated into DNA in place of normal bases
- base-modifying agents - modify the chemical structure & properties of bases, leading to mispairing during DNA replication & hence base substitutions
- intercalating agents - are flat molecules with multiple ring structures that insert themselves between adjacent bases in one or both strands of the DNA helix and lead to insertions/deletions during DNA synthesis and hence frameshift mutations

Question 19

what are chromosomal mutations/abberations?

Answer 19

a change in structure of chromosome or a change in the number of chromosomes

Question 20

what are the 4 kinds of changes in chromosome structure?

Answer 20

1. deletion
2. duplication
3. inversion
4. translocation

Question 21

what is chromosome deletion and its effect?

Answer 21

chromosome deletion is when a chromosome breaks in one or more places and a portion of it is lost.
the genotype is often altered when a deletion occurs due to the absence of certain gene loci. if deletion affects the same gene loci on both homologous chromosomes, it is usually lethal. if only one of a homologous pair is affected, the alleles on the non-deficient homologue will be expressed, even if recessive

Question 22

what is chromosome duplication and its effect?

Answer 22

chromosome duplication is when any part of the genetic material is present more than once.
results from unequal crossing over between synapsed chromosomes during meiosis.
may result in gene redundancy and phenotypic variations. duplications are also an important source of genetic variation during evolution

Question 23

what is chromosome inversion and its effect?

Answer 23

chromosome inversion is when a segment of a chromosome is turned around 180 degrees within a chromosome, rearranging the linear sequence of genetic information.
produces aberrant gametes that have a major impact on offspring
may result in position effects which lead to altered gene expression due to the positioning of a gene

Question 24

what is chromosome translocation?

Answer 24

chromosome translocation is the movement of a chromosomal segment to a new location in the genome. reciprocal translocation involves the exchange of segments between 2 non-homologous chromosomes
genetic information is not lost or gained; there is only a rearrangement of genetic material
may produce a position effect as it may realign certain genes in relation to others

Question 25

what are the 2 general types of changes in chromosome number?

Answer 25

1. aneuploidy (when an organism loses/gains one or more chromosomes)
2. polyploidy (when more than 2 multiples of the haploid chromosome set are found

Question 26

what are 2 types of aneuploidy?

Answer 26

1. monosomy - loss of a single chromosome. only occurs for x chromosome (45, x turner syndrome is when individuals only have 45 chromosomes including just 1 x chromosome). monosomy for any autosome is usually not tolerated in humans or other animals
2. trisomy - gain of one chromosome. eg 47, xxy klinefelter syndrome when people have more than one x chromosome. eg down syndrome, when people have extra chromosome 21

Question 27

what are 2 types of polyploidy?

Answer 27

1. autopolyploidy - the addition of one or more extra sets of chromosomes, identical to the normal haploid component of the same species. autotriploids may occur if chromosomes fail to separate during meiosis, or via experimental conditions by crossing with tetrapolyploids. autotetrapolyploids may be found in nature
2. allopolyploidy - combination of chromosome sets from different species may occur as a consequence of interspecific matings. comes from hybridization of 2 closely related species