Beruflich Dokumente
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Transversion
Pu to Pu - transion
uu u u
Generation of a 'nonsense'
mutation
• The wild-type DNA sequence
5'- CTA CAG ATT - 3'
3'- GAT GTC TAA - 5'
• Produces the mRNA 5'- CUA CAG AUU - 3'
which codes for the polypeptide
leu gln iso [etc]
• A 1st position mutation (C T) in the second
triplet gives a 'mutant' DNA sequence
sense strand 5'- CTA TAG ATT
- 3'
3'- GAT ATC TAA
- 5'
Produces the mRNA which 5'- CUA UAG
AUU - 3'
codes for the polypeptide leu- *
Generation of an 'amber suppressor'
mutation in a tRNA gene
• DNA sense strand 5'- TAC -3'
3'- ATG -5'
which produces the tRNA 3'- AUG -5'
anticodon loop
which reads the mRNA 5'- UAC -3'
as - tyr –
Abnormal splicing
EXON 1 EXON 2 EXON 3
β + thalassemia IVSI-
Frequency of Mutations
• Mutations are rare events.
• Humans inherit 3 x 109 bp from each parent. i.e.
each cell has 6 billion different bp that can be the
target of a substitution.
• Substitution occurs when DNA is being copied
(during S phase).
• No process is 100% accurate. So it is with DNA
replication.
• Errors occur at a rate of about 1 in every 50
million nucleotides added to the chain. (Not bad, I
wish I could type so accurately.)
• But with 6 X 109 bp in a human cell, it means
that each new cell contains some 120 new
mutations.
• Should we be worried? Probably not.
• Most our DNA does not encode anything. This
includes:
– Repetitive DNA(Alu-junk) –introns –synonymous codons
Somatic vs Germline
Mutations
• Mutations that occur in a somatic cell,
bone marrow or liver, may
•Damage the cell
•Make the cell cancerous
•Kill the cell
Whatever the effect, the ultimate fate of
that mutation is to disappear when the cell
in which it occurred , or its owner , dies
• Germline mutations, in contrast, will be
found in every descendant from zygote to
which that mutant gamete contributed. It
will be passed from one generation to the
Males contribute more
mutations than Females
• Most mutations occur during S phase of
cell division. Consequently males
should be more at risk because:
– Only two dozens or so mitotic
divisions occur from the fertilized egg
that starts embryonic developments
– The sperm of a 30 year old man in
contrast is the descendant of at least
400 mitotic divisions since the
fertilized egg that formed him
• The children of aged father suffer more
genetic disorders than those of young
Altered DNA-Altered
Protein
• A protein encoded by a gene that
contains a mutation is likely to be
abnormal.
• Sometimes the protein will be able to
function, but imperfectly.
• In other cases, it will be totally
disabled.
• The outcome depends not only on
how it alters a protein’s function but
Hereditary Mutations
• Gene mutations can be either
inherited or acquired
• Hereditary mutations are carried
in the DNA of the reproductive
cells
• When productive cells containing
mutations combine to produce
offspring, the mutation will be in
all of the offspring’s body cells
Acquired Mutations
• Acquired mutations are changes in
DNA that develop throughout a
person’s lifetime
• Although mistakes occur in DNA all
the time, a cell has the remarkable
ability to fix them
• But if the DNA repair mechanism
fails, mutations can be passed
along to future copies of the
altered cell
Alleles
• Genes come in pairs, with one copy
inherited from each parent.
• Many genes come in a number of variant
forms, known as alleles.
• A dominant allele prevails over a normal
allele.
• A recessive gene becomes apparent if its
counterpart allele on the other
chromosome becomes inactivated or lost.
• During formation of gametes, the
members of each pair separate, so as each
gamete carries one allele of each pair.
Allele pairs are restored at fertilization.
• Alleles of different genes reassort
Altered Dominant Genes