ch 18 Flashcards
Amyotrophic lateral sclerosis (ALS)
- a disease that in some people is caused
by an expanding nucleotide repeat mutation
Most cases are sporadic – no family history (10% appear as an autosomal dominant trait)
Typically, 2- 23 repeats of the nucleotide sequence GGGGGCC in this gene, 700-1600 repeats in those with ALS!
s translate additional proteins
that can be toxic to nerve cells
Mutation
an inherited change in genetic information – the
descendants that inherit the change may be cells or organisms
Mutations are both …
the sustainer of life (help to produce new genetic information to survive) and the cause of great
suffering! (can cause disease)
- Mutation is the source of all genetic variation – the raw
material of evolution!
* Also, the source of many diseases and disorders
Genetic Dissection
Mutations are useful for examining fundamental biological
processes.
Creating mutations to study their effects
take out one piece and see the affect that has
Somatic mutations
arise in somatic tissues (tissue arent producing gametes)
– The mutation is passed to the daughter cells, leading to genetically
identical mutant cells. earlier=more daughter cells
– Often no obvious effect on the phenotype because the function of
the mutant cell is taken over by a normal cell (or mutant cell dies).
– However, cells that stimulate cell division can give rise to cells with
selective advantage, as seen with cancer!
Germ-line mutations
– arise in cells that produce gametes
-affect single gene
-usually most mutations
– Can be passed to future generations, producing offspring that carry
the mutation in all their somatic and germ-line cells.
earlier we start=all cells have this mutation
gene mutation
– Mutations that affect a single gene
chromosome mutations.
– Mutations that affect the number or structure of chromosome
Base substitutions (point mutation)
alteration of a single
nucleotide in the DNA
Transitions - purine is replaced by a different purine (or
pyrimidine with a different pyrimidine)
Transversions - purine is replaced by a pyrimidine or vice
versa
Insertions and
deletions
(indels)
- The addition or
removal of one
(or more)
nucleotides - Most common
type of
mutation
Frameshift mutations
- Occur within sequences that encode proteins,
changing the reading frame of the gene. - Usually alter all amino acids encoded by the
nucleotides following the mutation – causing a drastic
effect on phenotype. - Some introduce premature stop codons – terminating
protein synthesis early, truncated protein
In-frame insertions and In-frame deletions
- Indels that do not affect the reading frame
- Insertions and deletions that consist of any multiple
of three nucleotides leave the reading frame intact
Expanding Nucleotide Repeats
- Increase in the number of copies of a set of nucleotides
- Most diseases caused by expansion of a set of three nucleotides (called a trinucleotide), most often CNG (”N” refers to any
nucleotide) - # of copies of the repeat often
correlates with the severity
* # of copies also correlates with its instability
- More repeats present,
probability of expansion to
even more repeats
increases! - Disease symptoms can be
produced in various ways –
some create toxic proteins,
others turn off transcription
Forward mutation
– mutation that alters the wild-type phenotype
Reverse mutation
– changes a mutant phenotype back to wild-type
Other terms are used to describe the effects of mutations on protein
structure.
Missense mutation
-base substitution changed the sequence now codes for different RNA brings in different amino acid sequence
Nonsense mutation
- still have mutation changed mRNA but now introduced a stop codon and told to stop because there’s no amino acid
Silent mutation
-do have a change on DNA but redundancy gives a buffer
Silent mutations many not be truly “silent”!
rate of protein slowed down due to tRNA
For example, when isoaccepting tRNAs bind to different
synonymous codons.
Some isoaccepting tRNAs are more abundant than others –
which synonymous codon is used may affect the rate of protein
synthesis.
Silent mutations may also alter nucleotides that serve as binding
sites for regulatory proteins, or alter exon/intron junctions that could
affect splicing.
Neutral mutation:
missense mutation that alters the amino acid sequence of a protein but does not change function
Neutral mutations occur when one amino acid is
replaced by another that is chemically similar, or when the affected amino acid has little influence on the protein function
ex: hemoglobin can still transport oxygen but amino acid altered
Loss-of-function mutations
– cause complete or partial
absence of normal protein function.
Alters structure of protein so no longer works
correctly.
Or, occurs in regulatory regions that affect
transcription, translation or splicing of protein.
Frequently recessive – diploid organisms must be
homozygous for mutation before the effects of the loss of functional protein can be exhibited.
Gain-of-function mutations
– causes cell to
produce protein/gene product whose function is
not normally present
Possibly entirely new gene product or one
produced in an inappropriate tissue or at
inappropriate time of development.
Frequently dominant in their expression – a single
copy leads to the presence of a new gene product.
Conditional mutation
– expressed only under
certain conditions (i.e. affect the phenotype only at
elevated temperatures)
Siamese cats have temp sensitive pigment that affects fur color (patterns on faces that appear based on temperature of area when born, see different levels of melanin synthesis)
