Gene Mutations Flashcards
How do mutations occur?
randomly
How often do mutations occur?
rarely
How do spontaneous mutations occur?
mutations that arise mainly through errors in DNA replication (without exposure to mutagens)
How do induced mutations arise?
through the exposure to mutagens (often called carcinogens)
When are mutations heritable?
When they occur in germ-line cells they will end up in sperm or egg and be passed on
When are mutations not heritable?
when they occur in somatic cells
How do mutations change the DNA?
Substitute
add
delete
one or more DNA base pairs
Where do point mutations occur?
at specific, identifiable position in a gene
or
a specific location in the genome
Describe base-pair substitution mutations
the replacement of one nucleotide base pair by another
What are the 3 types of base-pair substitution mutations?
synonymous
missense
nonsense
Describe synonymous mutations
a base-pair change that does not alter the result of the amino acid
Why do synonymous mutations occur?
because of the redundancy of the genetic code and the wobble position
Describe missense mutations
a base-pair change that results in an amino acid change in the protein
Describe nonsense mutations
base-pair change that creates a stop codon instead of a regular codon for an amino acid
Describe frameshift mutations
when there is an insertion or deletion of one or more base pairs in the coding region of a gene that changes the reading frame of the message
Where does the frameshift mutation occur? What does this change cause?
in the mRNA
it alters the reading frame of the message
What are the consequences of frameshift mutations?
premature stop codons can be produced
the wrong amino acid sequence can be produced starting from the point of mutation
Describe mutations in regulatory regions/noncoding regions
mutations that change the amount of protein produced by a gene but not the amino acid sequence
T or F: regulatory mutations change the amino acid sequence
false! they change the amount of protein produced by a gene
What regions can regulatory mutations affect?
promoters
introns
regions that code for 5’-UTR and 3’-UTR
Describe promoter mutations
mutations that alter consensus sequence nucleotides of promoters
What are the consequences of promoter mutations?
interference of transcription initiation:
mild-moderate reductions in transcription levels
stopping transcription
Describe splicing mutations
alterations of nucleotides (specific sequences) at either end of an intron
What are the consequences of splicing mutations?
Splicing errors
production of mutant proteins because introns aren’t spliced
What are the consequences of splice site mutations?
can dramatically change mRNA transcript
can cause large insertion or deletions in mature mRNA that may or may not be in frame
result in non-functioning proteins
What do splicing mutations often result in?
non-functioning proteins
Describe cryptic splice sites and how they form
new splice sites that can replace or compete with authentic splice sites formed by base-pair substitution during mRNA processing
Give an example of cryptic splice sites
A base-pair substitution that changes G to A at position 110 of human beta-globin intron 1 creates an AG splice site which leaves 19 additional nucleotides in the mature mRNA
Describe polyadenylation mutations
alteration of the signal sequence for the addition of the Poly-A tail at the 3’ end of eukaryotic mRNA which causes blocking of 3’ processing of mRNA
What consequences do polyadenylation mutations have?
they reduce the amount of protein produced:
reduce ability of mRNA to leave nucleus for translation
make mRNA more vulnerable to degradation before translation (parts of mRNA may be lost)
Describe a null mutation
When a mutation within a gene causes loss of function and produces no functional gene product
Describe leaky mutations
A mutation within a gene that causes partial loss of function and produces a partially functional gene product
Describe a silent mutation
a mutation within a gene that produces a normally functioning gene product
What does the severity of the phenotype of a leaky mutation depend on?
the level of activity of the gene product
What type of mutations will result in a null mutation product?
promoter mutations frameshift mutations nonsense mutations splicing mutations missense mutations (less common)
What type of mutation will cause leaky mutations?
missense mutations
What type of mutation will cause silent mutations?
synonymous mutations
What are the terms dominant and recessive based on?
phenotypes
What determines the dominance of one allele over another?
the protein product of the alleles
What are phenotypes the result of?
the activities of the protein products of the alleles of a gene
Are mutations of haplosufficient genes dominant or recessive?
recessive
What does a wild-type allele (R) produce in haplosufficient genes?
an active enzyme (50 units)
How many units does an active enzyme produced by a wild-type allele (R) in haplosufficient genes have?
50
What does a mutant allele (r) in haplosufficient genes produce?
no active enzyme (0 units)
How many units does an inactive enzyme produced by a mutant allele (r) in haplosufficient genes have?
0
How many units of enzyme activity are required to produce a wild-type phenotype in haplosufficient genes?
40+
How many functional copies of a gene is enough for normal function in heterozygotes with haplosufficient genes?
one
remember that Rr will display the dominant phenotype - only required one functional copy (R)
Are mutations of haploINsufficient genes dominant or recessive?
dominant
What does allele T1 in haploinsufficient genes produce?
an active enzyme (10 units)
How many units does an active enzyme from T1 allele in haploinsufficient genes produce?
10 units
What does the mutant allele T12 in haploinsufficient genes produce?
a less active enzyme (5 units)
How many units does the less active enzyme produced by mutant allele T2 in haploinsufficient genes have?
5 units
How many units of enzyme activity is required to produce the wild-type phenotype in haploinsufficient genes?
18+ (only T1T1 individuals are WT)
Using the T1 and T2 key, what genotype would individuals with haploinsufficient genes have to have to express the WT phenotype?
T1T1 (homozygous) because the mutation (T2) is dominant in haploinsufficient genes
Using the T1 and T2 key, what genotype would individuals with haploinsufficient genes have to have to express the mutant phenotype?
either T1T2 or T2T2 because neither produces enough enzyme to make the WT phenotype
In haploinsufficient genes, how many functional copies of a gene are required for normal functioning (the production of the WT phenotype)?
More than 1
