Human Genetics
Section 13.3: Mutations
Section 14.1: Human Chromosomes
Section 14.2: Human Genetic Disorders
Mutations
Section 13.3
Vocabulary
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Mutation
Germ Mutation
Somatic Mutation
Gene Mutation
Chromosomal
Mutation
Point Mutation
Frameshift Mutation
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Deletion
Duplication
Inversion
Translocation
Nondisjunction
Monosmy
Trisomy
Polyploidy
Types of Mutations
Mutations are heritable changes in genetic
information.
 A mutation results from a mistake in
duplicating genetic information
(DNA replication).
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Types of Cells Affected
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Germ Mutation - affects a reproductive cell
(gamete or sperm/egg)
◦ Does not affect the organism
◦ Passed to offspring

Somatic Mutation – affects body cells
(all cells except gametes)
◦ Not passed to offspring
Types of Mutations
 All mutations fall into two basic categories:
◦ Those that produce changes in a single gene are
known as gene mutations.
◦ Those that produce changes in a part of a
chromosome, whole chromosomes, or sets of
chromosomes are known as chromosomal
mutations.
Ameoba Sisters – Mutations (7 min)
Mutagens
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Mutations can be caused by chemical or physical agents
(mutagens)
◦ Chemical – pesticides, tobacco smoke, environmental pollutants
◦ Physical – X-rays and ultraviolet light
Gene Mutations
Mutations that involve changes in one or a few
nucleotides are known as point mutations
because they occur at a single point in the DNA
sequence. They generally occur during
replication.
 If a gene in one cell is altered, the alteration can
be passed on to every cell that develops from
the original one.
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Gene Mutations
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Point mutations include substitutions, insertions,
and deletions.
Substitutions
In a substitution, one base is changed to a
different base.
 Substitutions usually affect no more than a
single amino acid, and sometimes they have no
effect at all.
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Substitution - Silent Mutation
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a change in one base pair has no effect on the protein
produced by the gene.
◦ This is allowed for by the redundancy in the genetic code.
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Example (as shown in picture):
◦ Both GGC and GGU code for the amino acid glycine.
◦ Thus, the mutation is “silent,” i.e. causes no change in the
final protein product.
Substitution - Missense Mutation
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a change in one base pair causes a single amino
acid to be changed in the resulting protein.
◦ The result is called “missense” since the code is now
different.
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In the following example, GGC has been changed
to AGC, resulting in a different amino acid.
Substitutions - Missense
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In this example, the base cytosine is replaced by the
base thymine, resulting in a change in the mRNA codon
from CGU (arginine) to CAU (histidine).
Sickle Cell Anemia
The effect of a missense mutation on
the protein is unpredictable.
 A missense mutation is the cause of the
disease, sickle cell anemia.
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◦ a change in one base pair alters one amino
acid
◦ effects hemoglobin protein, causing red blood
cells to take on a strange shape
Sickle Cell
Anemia
Substitution - Nonsense Mutation
a change in a single base pair creates a
stop codon.
 Because this kind of mutation creates a
stop signal in the middle of a normally
functional gene, the resulting protein is
almost always nonfunctional
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◦ hence the term “nonsense” mutation.
Substitution
Silent
Mutation
Missense
Mutation
Nonsense
Mutation
Insertions and Deletions
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Insertions and deletions are point mutations in which
one base is inserted or removed from the DNA
sequence.
If a nucleotide is added or deleted, the bases are still
read in groups of three, but now those groupings shift in
every codon that follows the mutation.
Frameshift Mutation
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Insertions and deletions are also called frameshift
mutations because they shift the “reading frame” of
the genetic message.
Frameshift mutations can change every amino acid that
follows the point of the mutation and can alter a
protein so much that it is unable to perform its normal
functions.
Frameshift Mutation:
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Example:
◦ Deletion:
 THE FAT CAT ATE THE RAT
 THE FAT ATA TET HER AT
◦ Insertion:
 THE FAT CAT ATE THE RAT
 THE FAT CAR TAT ETH ERA T
Insertions
Deletions
Gene Mutations:
Chromosomal Mutations
Chromosomal mutations involve changes in the
number or structure of chromosomes.
 These mutations can change the location of
genes on chromosomes and can even change
the number of copies of some genes.
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Chromosomal Mutations
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Deletion involves the loss of all or part of
a chromosome.
Chromosomal Deletion
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Example: Cri-du-chat (5p minus) – a piece of
chromosome 5
Cri du chat
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intellectual disability/delayed development
small head size (microcephaly),
low birth weight
weak muscle tone (hypotonia) in infancy
widely set eyes (hypertelorism)
low-set ears
a small jaw
a rounded face
heart defect
Chromosomal Mutations
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Duplication produces an extra copy of all
or part of a chromosome.
Chromosomal Duplication
Fragile X - Most people have 29
"repeats" at this end of their Xchromosome, those with Fragile X
have over 700 repeats due to
duplications
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Fruit flies
experience
a change in
eye size of
when
duplication
occurs.
Chromosomal Mutations
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Inversion reverses the direction of parts of a
chromosome.
Chromosomal Inversion
Chromosomal Mutations
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Translocation occurs when part of one
chromosome breaks off and attaches to
another. Example: acute meyloid leukemia
Chromosomal Translocation
Inversions
Nondisjunction
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Chromosomal mutations that involve whole
chromosomes or complete sets of
chromosomes results from a process known as
nondisjunction
◦ This is the failure of homologous chromosomes to
separate normally during meiosis.
Nondisjunction
Nondisjunction
Nondisjunction
Effects of Nondisjunction
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If one chromosome is involved, the condition of
one extra is called trisomy or one less is
monosomy
Trisomy 21
Patau Syndrome (trisomy 13) serious eye, brain, circulatory defects as
well as cleft palate. 1:5000 live births.
Children rarely live more than a few
months
Edward’s Syndrome (trisomy 18) almost every organ system affected
1:10,000 live births. Children generally
do not live more than a few months
Trisomy X (XXX)
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females. 1:1000
live births healthy and
fertile - usually
cannot be
distinguished
from normal
female except
by karyotype
Monosomy X aka Turner Syndrome
the only viable
monosomy in humans
 only 45 chromosomes
 genetically female,
however, they do not
mature sexually during
puberty and are sterile.
 Short stature and
normal intelligence
 98% of these fetuses
die before birth
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Klinefelter Syndrome (XXY)
Affects male sex
organs (small testes,
sterile).
 feminine body
characteristics.
 Normal intelligence.
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Nondisjunction
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If nondisjunction involves a set of
chromosomes:
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The condition in which an organism has extra sets of
chromosomes is called polyploidy.
◦ Triploid (3n)
◦ Tetraploid (4n)
◦ Polyploid (many sets)
Beneficial Effects
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Plant and animal breeders often make use of “good”
mutations.
For example, when a complete set of chromosomes fails
to separate during meiosis, the gametes that result may
produce triploid (3N) or tetraploid (4N) organisms.
Beneficial Effects
Polyploid plants are often larger and stronger
than diploid plants.
 Important crop plants—including bananas and
limes—have been produced this way.
 Polyploidy also occurs naturally in citrus plants,
often through spontaneous mutations.
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Harmful and Helpful Mutations
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The effects of mutations on genes vary widely. Some
have little or no effect; and some produce beneficial
variations. Some negatively disrupt gene function.
Whether a mutation is negative or beneficial depends
on how its DNA changes relative to the organism’s
situation.
Mutations are often thought of as negative because they
disrupt the normal function of genes.
However, without mutations, organisms cannot evolve,
because mutations are the source of genetic variability
in a species.
Harmful Effects
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Sickle cell disease is a disorder associated with changes
in the shape of red blood cells. Normal red blood cells
are round. Sickle cells appear long and pointed.
Sickle cell disease is caused by a point mutation in one
of the polypeptides found in hemoglobin, the blood’s
principal oxygen-carrying protein.
Among the symptoms of the disease are anemia, severe
pain, frequent infections, and stunted growth.
Substitution
Beneficial Effects
Some of the variation produced by mutations can be
highly advantageous to an organism or species.
 Mutations often produce proteins with new or altered
functions that can be useful to organisms in different or
changing environments.
 For example, mutations have helped many insects resist
chemical pesticides.
 Some mutations have enabled microorganisms to adapt
to new chemicals in the environment.
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Human Chromosomes
Section 14.1
Vocabulary
Karyotype
 Sex Chromosomes
 Autosomes
 Linked Genes
 Sex-Linked Inheritance
 Pedigree
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Karyotypes
A karyotype shows the complete diploid set
of chromosomes grouped together in pairs,
arranged in order of decreasing size.
 To see human chromosomes clearly, cell
biologists photograph cells in mitosis, when the
chromosomes are fully condensed and easy to
view.
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Karyotypes
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A karyotype from a typical human cell, which
contains 46 chromosomes, is arranged in 23
pairs.
Sex Chromosomes
Two of the 46 chromosomes in the human
genome are known as sex chromosomes,
because they determine an individual’s sex.
 Females have two copies of the X chromosome.
 Males have one X chromosome and one Y
chromosome.
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Sex Chromosomes
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This Punnett square illustrates
why males and females are
born in a roughly 50 : 50 ratio.
All human egg cells carry a
single X chromosome (23,X).
However, half of all sperm cells
carry an X chromosome
(23,X) and half carry a
Y chromosome (23,Y).
This ensures that just about half the zygotes will be
males and half will be females.
Sex Chromosomes
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More than 1200 genes are
found on the X chromosome,
some of which are shown.
The human Y chromosome is
much smaller than the
X chromosome and contains
only about 140 genes, most
of which are associated with
male sex determination and
sperm development.
Autosomal Chromosomes
The remaining 44 human chromosomes are known as
autosomal chromosomes, or autosomes.
 The complete human genome consists of 46
chromosomes, including 44 autosomes and 2 sex
chromosomes.
 To quickly summarize
the total number of
chromosomes present
in a human cell, biologists
write 46,XX for females
and 46,XY for males.
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Linked Genes
Genes on chromosomes are linked together &
inherited together
 Chromosomes assort independently, not
individual genes
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Gene Mapping
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In 1911, Columbia University student Alfred Sturtevant
wondered if the frequency of crossing-over between
genes during meiosis might be a clue to the genes’
locations.
Sturtevant reasoned that the farther apart two genes
were on a chromosome, the more likely it would be
that a crossover event would occur between them.
If two genes are close together, then crossovers
between them should be rare. If two genes are far apart,
then crossovers between them should be more
common.
Gene Mapping
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By this reasoning, he could use
the frequency of crossing-over
between genes to determine
their distances from each
other.
Sturtevant gathered lab data and presented a gene
map showing the relative locations of each known
gene on one of the Drosophila chromosomes.
Sturtevant’s method has been used to construct
gene maps ever since this discovery.
Sex-Linked Inheritance
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The genes located on the X and Y chromosomes
show a pattern of inheritance called sex-linked.
A sex-linked gene is a gene located on a sex
chromosome.
Genes on the Y chromosome are found only in
males and are passed directly from father to son.
Genes located on the X chromosome are found in
both sexes, but the fact that men have just one X
chromosome leads to some interesting
consequences.
Sex-Linked Inheritance
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For example, humans have three genes responsible for
color vision, all located on the X chromosome.
In males, a defective allele for any of these genes results
in colorblindness, an inability to distinguish certain
colors. The most common form, red-green
colorblindness, occurs in about 1 in 12 males.
Among females, however, colorblindness affects only
about 1 in 200. In order for a recessive allele, like
colorblindness, to be expressed in females, it must be
present in two copies—one on each of the X
chromosomes.
The recessive phenotype of a sex-linked genetic
disorder tends to be much more common among males
than among females.
X-Chromosome
Inactivation
If just one X chromosome is enough for cells in
males, how does the cell “adjust” to the extra X
chromosome in female cells?
 In female cells, most of the genes in one of the
X chromosomes are randomly switched off,
forming a dense region in the nucleus known as
a Barr body.
 Barr bodies are generally not found in males
because their single X chromosome is still
active.
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Human Pedigrees
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To analyze the pattern of inheritance followed by a
particular trait, you can use a chart, called a pedigree,
which shows the relationships within a family.
A pedigree shows the presence or absence of a trait
according to the relationships between parents, siblings,
and offspring.
Human Genetic
Disorders
Section 14.2
THINK ABOUT IT
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Have you ever heard the expression “It runs in
the family”?
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Relatives or friends might have said that about
your smile or the shape of your ears, but what
could it mean when they talk of diseases and
disorders?
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What is a genetic disorder?
Chromosomal Disorders
Single Gene Disorders
Down Syndrome
 Turner Syndrome
 Klinefelter’s Syndrome
 Jacobson’s
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Sickle Cell Disease
 Cystic Fibrosis
 Huntington’s
Genetic Disorders
Chromosomal Disorders
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The most common error in
meiosis occurs when
homologous chromosomes
fail to separate. This mistake
is known as nondisjunction,
which means “not coming
apart.”
Nondisjunction may result in
gametes with an abnormal
number of chromosomes, which can lead to a disorder
of chromosome numbers.
Karyotype:
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Down Syndrome
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Turner Syndrome
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Klinefelter’s Syndrome
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Jacobson’s
Chromosomal Disorders
If two copies of an autosomal chromosome fail to
separate during meiosis, an individual may be born with
three copies of that chromosome.
 This condition is known as a trisomy, meaning “three
bodies.”
 The most common form of trisomy, involving three
copies of chromosome 21, is Down syndrome, which is
often characterized by mild to severe mental
retardation and a high frequency of certain birth
defects.
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Chromosomal Disorders
Nondisjunction of the X chromosomes can lead
to a disorder known as Turner’s syndrome.
 A female with Turner’s syndrome usually
inherits only one X chromosome.
 Women with Turner’s syndrome are sterile,
which means that they are unable to reproduce.
Their sex organs do not develop properly at
puberty.
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Chromosomal Disorders
In males, nondisjunction may cause Klinefelter’s
syndrome, resulting from the inheritance of an
extra X chromosome, which interferes with
meiosis and usually prevents these individuals
from reproducing.
 There have been no reported instances of
babies being born without an X chromosome,
indicating that this chromosome contains genes
that are vital for the survival and development
of the embryo.
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From Molecule to Phenotype
There is a direct connection between molecule
and trait, and between genotype and phenotype.
In other words, there is a molecular basis for
genetic disorders.
 Changes in a gene’s DNA sequence can change
proteins by altering their amino acid sequences,
which may directly affect one’s phenotype.
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Patterns of Inheritance:
1. Autosomal Dominant
 2. Autosomal Recessive
 3. Sex-Linked (X-Linked)
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Autosomal Dominant
• Huntington’s, Achondroplasia. Polydactyly, Myopia
Huntington’s Disease
Huntington’s disease is caused by a dominant allele for a
protein found in brain cells.
 The allele for this disease contains a long string of bases
in which the codon CAG—coding for the amino acid
glutamine—repeats over and over again, more than 40
times.
 Despite intensive study, the reason why these long
strings of glutamine cause disease is still not clear.
 The symptoms of Huntington’s disease, namely mental
deterioration and uncontrollable movements, usually do
not appear until middle age.
 The greater the number of codon repeats, the earlier
the disease appears, and the more severe are its
symptoms.
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Autosomal Recessive Pedigree:
Albinism,
Cystic Fibrosis,
Phenylketonuria,
Sickle Cell Anemia,
Tay Sachs
Sickle Cell Disease
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This disorder is caused by a defective allele for betaglobin, one of two polypeptides in hemoglobin, the
oxygen-carrying protein in red blood cells.
The defective polypeptide makes hemoglobin less
soluble, causing hemoglobin molecules to stick together
when the blood’s oxygen level decreases.
The molecules clump into long fibers, forcing cells into a
distinctive sickle shape, which gives the disorder its
name.
Sickle Cell Disease
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Sickle-shaped cells are more rigid than normal red
blood cells, and they tend to get stuck in the capillaries.
If the blood stops moving through the capillaries,
damage to cells, tissues, and even organs can result.
Cystic Fibrosis
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Cystic fibrosis (CF) is most common among people of
European ancestry.
Most cases result from the deletion of just three bases
in the gene for a protein called cystic fibrosis
transmembrane conductance regulator (CFTR). As a
result, the amino acid phenylalanine is missing from the
protein.
Cystic Fibrosis
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CFTR normally allows chloride ions (Cl−) to pass across
cell membranes.
The loss of these bases removes a single amino acid—
phenylalanine—from CFTR, causing the protein to fold
improperly.
Cystic Fibrosis
People with one normal copy of the CF allele
are unaffected by CF, because they can produce
enough CFTR to allow their cells to work
properly.
 Two copies of the defective allele are needed to
produce the disorder, which means the CF allele
is recessive.
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Sex-Linked Pedigree:
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Colorblindness, Hemophilia, Muscular Dystrophy
Genetic Advantages
Disorders such as sickle cell disease and CF are
still common in human populations.
 In the United States, the sickle cell allele is
carried by approximately 1 person in 12 of
African ancestry, and the CF allele is carried by
roughly 1 person in 25 of European ancestry.
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Genetic Advantages
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Most African Americans today
are descended from
populations that originally
lived in west central Africa,
where malaria is common.
Malaria is a mosquito-borne
infection caused by a parasite
that lives inside red blood
cells.
Genetic Advantages
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Individuals with just one copy
of the sickle cell allele are
generally healthy, and are also
highly resistant to the
parasite, giving them a great
advantage against malaria.
The upper map shows the
parts of the world where
malaria is common. The
lower map shows regions where people have the sickle
cell allele.
Genetic Advantages
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More than 1000 years ago, the cities of medieval
Europe were ravaged by epidemics of typhoid fever.
Typhoid is caused by a bacterium that enters the
body through cells in the digestive system.
The protein produced by the CF allele helps block
the entry of this bacterium.
Individuals heterozygous for CF would have had an
advantage when living in cities with poor sanitation
and polluted water, and—because they also carried
a normal allele—these individuals would not have
suffered from cystic fibrosis.