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MUTATIONS
HE.5.B.5
HE.5.B.6
What makes them different?
Mutations
• Now and then cells make mistakes in copying their
own DNA. These mistakes are called mutations.
• Change in a DNA sequence that affects genetic
information. (pg. 307)
There are 2 kinds of mutation
• Gene mutation
• Chromosomal mutation
Gene Mutations
Chromosomal mutations:
Gene mutation
• Mutations that produce changes in a single gene.
Ex. Gene Mutation: Huntington’s Disease
• Affects a person's ability to think, talk, and move.
• Destroys cells in the basal ganglia, the part of the brain
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that controls movement, emotion, and cognitive ability.
Caused by a mutation in a gene on chromosome 4.
Autosomal Dominant Inheritance.
Normally, the coding region of this gene contains the
DNA sequence "CAG" repeated again and again. The
number of times this triplet is repeated varies from person
to person, ranging from 10 to 26 times. People with HD
have an abnormally high number of these CAG triplets,
approximately 40 or more.
This likely disrupts the function of the gene's protein
product.
Somehow the brain cells of HD patients accumulate
clumps of protein that become toxic, resulting in cell
death. Some patients lose more than 25% of their brain
cells before they die.
Chromosomal mutations
• Produce changes in a whole chromosome.
Gene mutations
• Point mutations
• Substitution
• Insertion
• Deletion
Single Gene Mutations
Out of the 3 gene mutations which 2 are the most dramatic? Why?
Point mutations
• Gene mutation involving changes in one or a few
nucleotides.
Frameshift mutations
• Insertion and deletion cause a shift in the “reading
frame” of the genetic message.
• This kind of mutation may change every amino acid
that follows the point mutation.
Gene Mutations Activity
Chromosomal mutations
• Involve changes in the number or structure of
chromosomes.
4 types of chromosomal mutations
• Deletion
• Duplication
• Inversion
• Translocation
Chromosomal Mutations
Chromosomal mutation: Deletion
• Loss of all or part of a chromosome
Ex of Deletion: Williams Syndrome
• Rare genetic disorder that affects a child's
growth, physical appearance, and cognitive
development.
• Missing genetic material from chromosome 7,
including the gene elastin.
• This gene's protein product gives blood vessels
the stretchiness and strength required to
withstand a lifetime of use. The elastin protein is
made only during embryonic development and
childhood, when blood vessels are formed.
Because they lack the elastin protein, people
with Williams Syndrome have disorders of the
circulatory system and heart.
Williams Syndrome
• A deletion is caused by a
break in the DNA molecule
that makes up a
chromosome. In most cases,
the chromosome break
occurs while the sperm or
egg cell (the male or female
gamete) is developing.
When this gamete is
fertilized, the child will
develop Williams syndrome.
• It is possible for a child to
inherit a broken
chromosome from a parent
who has the disorder. But this
is rare because most people
with Williams syndrome do
not have children.
Chromosomal mutation: Duplication
• Produces extra copies or parts of a chromosome.
Chromosomal mutation: Inversion
• Reverse the direction of parts of the chromosome.
Inversion cont.
• In most species small inversions go undetected.
• Inversions usually do not cause any abnormalities in
carriers as long as the rearrangement is balanced with no
extra or missing DNA.
• Individuals which are heterozygous for an inversion, there
is an increased production of abnormal chromatids (this
occurs when crossing-over occurs within the span of the
inversion). This leads to lowered fertility due to production
of unbalanced gametes.
• The most common inversion seen in humans is
on chromosome 9. This inversion is generally considered to
have no harmful effects, but there is some suspicion it
could lead to an increased risk for miscarriage or infertility
for some affected individual.
Chromosomal mutation: Translocation
• Part of a chromosome breaks off and attaches to
another.
Ex. Of Translocation
• Cancer: Several forms of cancer are caused by acquired
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translocations (as opposed to those present from
conception); this has been described mainly
in leukemia (acute myelogenous leukemia and chronic
myelogenous leukemia).
Infertility: One of the would-be parents carries a balanced
translocation, where the parent is asymptomatic but
conceived fetuses are not viable.
Down syndrome is caused in a minority (5% or less) of cases
by a translocation of the chromosome 21 long arm onto
the long arm of chromosome 14.[5]
Chromosomal translocations between the sex
chromosomes can also result in a number of genetic
conditions, such as
XX male syndrome: caused by a translocation of
the SRY gene from the Y to the X chromosome
XX male syndrome (Translocation)
• Caused by unequal crossing over between X and Y
chromosomes during meiosis in the father, which results in the X
chromosome containing the normally-male SRY gene. When this X
combines with a normal X from the mother during fertilization, the
result is an XX male.
• This syndrome occurs in approximately four or five in 100,000
individual.
• Symptoms usually include small testes and subjects are
invariably sterile. Individuals with this condition sometimes have
feminine characteristic.
Non-disjunction
• Happens in chromosomes, when cells are going
through meiosis.
Human Karyotype
Trisomy
Monosomy
Mutations can be:
• Neutral
• Harmful
• Beneficial
Neutral (not good or bad Ø)
• Most common.
• Have little or no effect on the expression of genes or the
function of the proteins for which they code.
Harmful (bad -)
• Often caused by dramatic changes in protein structure or
gene activity.
• Produce defective proteins that disrupt normal biological
activities.
• Often the cause of many genetic disorders.
• Many cancers are due to harmful mutations.
Beneficial (good +)
• Source of genetic variability in a species.
• Beneficial mutations may produce proteins with new or altered
activities that can be useful to organisms in different or changing
environment.
Questions - Identify the mutations
below as neutral (N), harmful (H) or
beneficial (B)
• A specific 32 base pair deletion in human CCR5
(CCR5-Δ32) confers HIV resistance to homozygotes
and delays AIDS onset in heterozygotes.
• Individuals with two alleles of the sickle-cell disease
have sickle-cell disease.
• Individuals with only one of the two alleles of the
sickle-cell disease are more resistant to malaria
• A mutation on the last nucleotide on GGU.
• Color-blindness is caused by the mutation of a single
gene.