Transcript Human Genetics PowerPoint

Activating Prior Knowledge
Human Genetics Notes
Proteins
Elements: Carbon, Hydrogen, Oxygen, Nitrogen
 Monomer: AMINO ACID (20 different kinds)
 Each amino acid has a central carbon atom
bonded to 4 other atoms or functional groups
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Nucleic Acids
Large, complex organic compounds that store
information in cells, using a system of four
compounds to store hereditary information, arranged
in a certain order as a code for genetic instructions of
the cell.
 Elements: Carbon, Hydrogen,
Oxygen, Nitrogen, Phosphorus
 Monomer: Nucleotide
1. Phosphate group
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(Phosphoric Acid)
5-carbon (pentose) sugar
(Deoxyribose or Ribose)
3. Nitrogenous Base
2.
There are 4
Nitrogenous Bases
There are FOUR Nitrogen bases
Nitrogen bases pair according to certain rules:
a) Purines pair with
pyrimidines
b) Guanine pairs with Cytosine
and Thymine pairs with
Adenine
The nitrogen bases are held
together by hydrogen bonds.
DNA Replication
Because each of the two strands of the
DNA double helix has all of the
information to reconstruct the other half,
the strands are said to be
complementary.
 Each strand of the double helix serves as a
template to make the other strand.
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S Phase: DNA Replication
 In
the S (or
synthesis) phase,
new DNA is
synthesized when
the chromosomes
are replicated.
3 differences between DNA and
RNA:
1. RNA is single stranded, DNA
is double stranded
2. RNA contains uracil in place of
thymine
3. 5-carbon sugar is ribose in RNA,
deoxyribose in DNA
Amoeba Sisters: DNA vs. RNA (4:43)
RNA Synthesis: Transcription
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All 3 types of RNA are synthesized from DNA
in the nucleus and then used to synthesize
proteins in the ribosome.
Protein synthesis is a two step process:
1) Transcription: DNA  mRNA (nucleus)
2) Translation: mRNA  amino acids 
proteins (ribosome)
DNA Transcription and Protein Assembly (3:01)
Protein Synthesis:
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Translation involves mRNA, rRNA, and tRNA.
Transfer RNA (tRNA) carries the amino acids to the ribosome
(different tRNA for each amino acid)
Ribosomal RNA (rRNA) makes up the major part of the
ribosome.
Three sequential nucleotides on a tRNA molecule are called an
anticodon.
The anticodon on the tRNA is complementary to the codon of
mRNA.
Protein Synthesis:
There are 64 different
codons.
 Each codon specifies a
particular amino acid
that is to be placed in
the polypeptide chain.
 AUG is the “initiator”
codon.
 There are 3 “stop”
codons.
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Diploid Cells
A cell that contains both
sets of homologous
chromosomes is diploid,
meaning “two sets.”
 The diploid number of
chromosomes is
represented by 2N.
 For humans, the diploid
number is 46 (2N = 46)
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Haploid Cells
Some cells contain only a single set of
chromosomes = a single set of genes.
 Such cells are haploid, meaning “one set.”
 The gametes (egg and sperm) of sexually
reproducing organisms are haploid.
 For humans, the haploid number is 23 (N = 23).
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Formation of Gametes –
Egg and Sperm
Spermatogenesis
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Forms 4 haploid sperm
Oogenesis
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Forms 1 ovum (egg) and 3
polar bodies
Oogenesis (3:53)
Cell Division
The chromosomes separate
and begin to move to
opposite sides of the cell
13) The chromosomes become
visible. The centrioles take up
positions on opposite sides
of the nucleus.
14) A nuclear envelope reforms
around each cluster of
chromosomes. The nucleolus
becomes visible in each
daughter nucleus.
15) The chromosomes line up
across the center of the cell.
12)
12)
Anaphase
13)
Prophase
14)
Telophase
15)
Metaphase
Mitosis or Meiosis
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17)
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19)
20)
21)
22)
23)
Four new cells are formed from each
original
This process makes sperm cells
Two new cells are produced from each
original
New skin cells are made this way
This type of reproduction helps you
grow
This type of cell reproduction makes egg
cells
Makes cells with half the original
chromosome number
Makes cells with the same chromosome
number as the original.
16)
Meiosis
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Meiosis
18)
Mitosis
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Mitosis
20)
Mitosis
21)
Meiosis
22)
Meiosis
23)
Mitosis
Segregation – Anaphase I & II
During anaphase I, spindle fibers pull each
homologous chromosome pair toward opposite
ends of the cell.
 During anaphase II, the paired chromatids
separate.
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Prophase I
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The cells begin to divide, and the
chromosomes pair up, forming a structure
called a tetrad, which contains 4 chromatids.
As homologous chromosomes pair up and
form tetrads, they undergo a process called
crossing-over.
Genotype vs. Phenotype:
Genotype: Genetic make-up of an organism
(Ex: Aa, BB, cc)
 Phenotype: Physical characteristics of an
organism (Ex: flower color, eye color)
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Homozygous (Purebred) vs.
Heterozygous (Hybrid):
Organism that has two identical alleles for a
particular trait. (Ex: AA, bb, CC, dd)
 Organism that has two different alleles for the
same gene. (Ex: Aa, Bb, Cc, Dd)
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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
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
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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
Animated Intro to Cancer
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.
Substitution
Silent
Mutation
Missense
Mutation
Nonsense
Mutation
Substitution
Sickle Cell
Anemia
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.
Muscular Dystrophy
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Both Duchenne muscular dystrophy and Becker muscular dystrophy result
from mutations of a gene on the X chromosome that codes for the
dystrophin protein in muscle cells; this protein helps to stabilize the plasma
membrane during the mechanical stresses of muscle contraction.
◦ About 2/3 of cases are due to deletion mutations.
If the number of nucleotides deleted in the mRNA is not a multiple of three,
this type of FRAMESHIFT mutation results in a severely defective or absent
version of the protein, resulting in more rapid breakdown of muscle cells and
the more severe DUCHENNE muscular dystrophy.
 If the number of nucleotides deleted in the mRNA is a multiple of three, the
mutation does not cause a frameshift and this typically results in a less
defective version of the protein, less rapid breakdown of muscle cells, and the
milder BECKER muscular dystrophy.
 Up to one-fifth of cases of Duchenne muscular dystrophy are caused by a
nonsense mutation (a point mutation that results in a stop codon).
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Muscular Dystrophy
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Because the dystrophin gene is on the X
chromosome and because the alleles for
defective dystrophin are recessive, both of
these types of muscular dystrophy are much
more common in boys than in girls. Duchenne
muscular dystrophy affects one in every 3500
male babies.
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
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.
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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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Summary of Mendel’s Principles
Law of Dominance: Some alleles are
dominant and others are recessive.
 Law of Segregation: Each adult has two
alleles for each gene but they can only pass
on one.
 Law of Independent Assortment:
Each gene is inherited independently of
each other.
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Independent Assortment
How do alleles segregate if more that one gene is involved?
◦ Does the seed shape gene influence the seed color gene?
◦ Blue eyes, blonde hair? Brown hair, brown eyes?
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Principle of Independent assortment – genes for
different traits can segregate independently during the
formation of the gametes
◦ Seed shape & color gene do not influence each other
NORMAL
Gene Linkage
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Thomas Hunt Morgan discovered that
many genes in fruit flies were
inherited together.
◦ Ex: Flies with reddish-orange eyes almost
always had miniature wings
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Vestigial wing
This seemed to violate the principle of
independent assortment.
Gene Map – shows
the location of a
variety of genes on
chromosome 2 of
the fruit fly.
Orange eyes – defect
in white gene
Linked Genes
Morgan’s findings lead to 2 conclusions:
1. Each chromosome is a group of linked
genes
2. Chromosomes assort independently, not
the individual genes.
When two genes are close together on the
same chromosome, they do not assort
independently and are said to be linked.
Gene Mapping
Gene Maps: show the relative location of each
gene on a chromosome.
 Looking at the parents chromosomes, explain why
short legs and purple eyes are more likely to be
inherited together than short legs and vestigial
wings.
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Gene Mapping
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Scientist realized that the further
apart the two genes were on a
chromosome, the more likely that
crossing over would occur
between them.
They could used the frequency of
crossing over between genes to
determine their distance from each
other.
◦ If genes were close then a
crossover between them would
be rare.
◦ If genes were far apart then a
crossover between them would
be more likely.
Chromosomal 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 (“cry of the cat”)
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named for the distinctive cry affected infants make due in part to
malformations of the larynx
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
Jacobsen’s
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caused by a loss of genetic material from chromosome 11 - deletion
occurs at the end of the long arm of chromosome 11
The signs and symptoms vary:
◦ delayed development, including the development of motor skills (such as sitting,
standing, and walking) and speech.
◦ cognitive impairment and learning difficulties.
◦ behavioral problems and attention deficit-hyperactivity disorder (ADHD).
◦ small and low-set ears, widely set eyes) with droopy eyelids, skin folds covering the
inner corner of the eyes
◦ a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small
lower jaw, large head size and a skull abnormality, which gives the forehead a pointed
appearance.
◦ bleeding disorder called Paris-Trousseau syndrome - causes a lifelong risk of
abnormal bleeding and easy bruising.
◦ heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus
infections, and skeletal abnormalities, can also affect the digestive system, kidneys,
and genitalia.
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The life expectancy of people with Jacobsen syndrome is unknown,
although affected individuals have lived into adulthood.
Williams Syndrome
Williams syndrome is caused by the
deletion of genetic material from a portion
of the long (q) arm of chromosome 7.
 The deleted region includes 26 to 28 genes,
and researchers believe that the
characteristic features of Williams
syndrome are probably related to the loss
of several of these genes.
 https://williams-syndrome.org/what-iswilliams-syndrome
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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 5-40
"repeats" at this end of their Xchromosome, those with Fragile X
have over 200 repeats due to
duplications
Fragile X
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FMR1 gene where a DNA segment, known as the CGG triplet repeat, is
expanded
◦ The abnormally expanded CGG segment inactivates (silences) the FMR1 gene,
which prevents the gene from producing a protein called fragile X mental
retardation protein.
◦ Loss of this protein leads to the signs and symptoms of fragile X syndrome.
◦ Both boys and girls can be affected, but because boys have only one X
chromosome, a single fragile X is likely to affect them more severely.
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Boys will have moderate mental retardation, a large head size, a long face,
prominent forehead and chin and protruding ears, loose joints.
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Affected boys may have behavioral problems such as hyperactivity, hand flapping, hand biting, temper tantrums and
autism. Other behaviors in boys after they have reached puberty include poor eye contact, perseverative speech,
problems in impulse control and distractibility. Physical problems that have been seen include eye, orthopedic, heart
and skin problems.
Girls will have mild mental retardation.
Family members who have fewer repeats in the FMR1 gene may not have
mental retardation, but may have other problems.
Women with less severe changes may have premature menopause or
difficulty becoming pregnant.
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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
Inversions
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 individuals.
An inversion does not
involve a loss of genetic
information, but simply
rearranges the linear gene
sequence.
Chromosomal Mutations
Translocation occurs when part of a
chromosome breaks off and attaches to
another. Segments from two different
chromosomes have been exchanged.
 Example: acute meyloid leukemia
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Translocation
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Acute Meyloid Leukemia (AML)
◦ Between chromosome 8 and 21; 15 and 17
◦ is a cancer of the myeloid line of blood cells
◦ characterized by the rapid growth of abnormal
WBC that accumulate in the bone marrow and
interfere with the production of normal WBC
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Dermatofibrosarcoma – rare skin cancer
◦ Between chromosome 17 and 22
◦ Somatic mutation – acquired during a person’s
lifetime
Chromosomal Translocation
Chromosomal Mutation
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Insertion occurs when a portion of one
chromosome has been deleted from its
normal place and inserted into another
chromosome
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.
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
Effects of Nondisjunction
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If one chromosome is involved, the condition of
one extra chromosome is called trisomy or
one less chromosome is monosomy
Down Syndrome (Trisomy 21)
National Down Syndrome Society
• One in every 691 babies in
the US is born with Down
syndrome
• Down syndrome the most
common genetic
condition.
• ~400,000 Americans have
Down syndrome and
~6,000 babies with Down
syndrome are born in the
US each year.
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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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
Klinefelter Syndrome (XXY)
In males, nondisjunction may
cause Klinefelter’s syndrome,
resulting from the
inheritance of an extra X
chromosome (XXY), which
interferes with meiosis and
usually prevents these
individuals from
reproducing.
 Affects male sex organs
(small testes, sterile).
 feminine body
characteristics.
 Normal intelligence.
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Monosomy X (aka Turner Syndrome)
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Nondisjunction of the X
chromosomes can lead to a disorder
known as Turner’s syndrome
(Monosomy X).
the only viable monosomy in
humans
only 45 chromosomes
A female with Turner’s syndrome
usually inherits only one X
chromosome.
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
Jacob’s Syndrome (XYY)
XYY syndrome is a
rare chromosomal
disorder that affects
males. It is caused by
the presence of an
extra Y chromosome.
 Individuals are
somewhat taller than
average and often have
below normal
intelligence.
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Chromosomal Disorders
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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.
Nondisjunction
 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)
Harmful and Helpful Mutations
The effects of mutations on genes vary widely. Some have
little or no effect, some produce beneficial variations, and
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.
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Beneficial Effects
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Plant and animal breeders often make use of “good”
mutations.
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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, limes,
strawberries —have been
produced this way.
 Many species are thought
to be polyploids at some
point, but it is most
common in plants, with
the highest occurrence in
ferns and flowering plants.
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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.
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Mutations have helped many insects resist chemical
pesticides.
Some mutations have enabled microorganisms to adapt
to new chemicals in the environment.
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.
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
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.
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http://www.colourblindawareness.org/
http://www.neitzvision.com/content/home.html
Can you see the numbers contained
within this circle?
Colorblind Vision Tests
One or more sets of retinal cones that perceive color in
light and transmit that information to the optic nerve are
faulty.
 In a side-by-side comparison of a red Braeburn apple and
green Granny Smith apple, a normal color vision person
would see the apples as they appear on the top row.
 An individual who is red green color-blind would see
those same apples as they appear on the bottom row
and be unable to distinguish, by color, the Braeburn apple
from the Granny Smith
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Colorblindness
Normal Vision
Tritanopia
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?

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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Autosomes:
chromosome pairs 1-22
Sex Chromosomes:
chromosome pair 23
Down Syndrome
Turner Syndrome
Klinefelter’s Syndrome
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.

Down Syndrome (Trisomy 21)
National Down Syndrome Society
• One in every 691 babies in
the US is born with Down
syndrome
• Down syndrome the most
common genetic
condition.
• ~400,000 Americans have
Down syndrome and
~6,000 babies with Down
syndrome are born in the
US each year.
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.

Trisomy 21
Chromosomal Disorders
Nondisjunction of the X chromosomes can lead
to a disorder known as Turner’s syndrome
(Monosomy X).
 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.

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

Monosomy X (aka Turner Syndrome)







Nondisjunction of the X
chromosomes can lead to a disorder
known as Turner’s syndrome
(Monosomy X).
the only viable monosomy in
humans
only 45 chromosomes
A female with Turner’s syndrome
usually inherits only one X
chromosome.
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
Klinefelter Syndrome (XXY)
Affects male sex
organs (small testes,
sterile).
 feminine body
characteristics.
 Normal intelligence.

Chromosomal Disorders
In males, nondisjunction may cause Klinefelter’s
syndrome, resulting from the inheritance of an
extra X chromosome (XXY), 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.

Klinefelter Syndrome (XXY)
In males, nondisjunction may
cause Klinefelter’s syndrome,
resulting from the
inheritance of an extra X
chromosome (XXY), which
interferes with meiosis and
usually prevents these
individuals from
reproducing.
 Affects male sex organs
(small testes, sterile).
 feminine body
characteristics.
 Normal intelligence.

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)

females. 1:1000
live births healthy and
fertile - usually
cannot be
distinguished
from normal
female except
by karyotype
Jacob’s Syndrome (XYY)
XYY syndrome is a
rare chromosomal
disorder that affects
males. It is caused by
the presence of an
extra Y chromosome.
 Individuals are
somewhat taller than
average and often have
below normal
intelligence.

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.

Human Pedigrees


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.
Interpreting Pedigrees
What do these symbols mean?
Female unaffected
Female affected
Male unaffected
Male affected
Mating
Pedigree Interpretation
Pedigree #1
Dominant or Recessive?
Must be recessive because the parents do NOT have the trait but individual II, 1;
and II, 3 has the trait.
What is the genotype for each parent (I, 1 and 2)?
Autosomal or Sex-linked?
Autosomal
Heterozygous
Pedigree #2
Dominant or Recessive?
Dominant, because BOTH parents have the trait, but they were able to have
children (individuals II, 1 and II, 3) without the trait.
Autosomal or Sex-linked?
Autosomal because there are even number of males and females who have the trait.
Which individuals must be heterozygous?
Parents on the left
Pedigree #3
XT Xt
XT Xt
Xt Y
XT Xt
Xt Y
Xt Xt
XT Xt
Xt
Y
XT Y
XT Xt Xt Y
XT XT
XT Xt XT Xt X t Y
Dominant or Recessive? Autosomal vs. Sex-linked?
Recessive, sex linked.
Pedigree #4 (Problem #6 in HW)
1.
2.
3.
4.
How many generations are represented on this pedigree? 3
Is this a recessive or dominant trait? How can you tell? Recessive
Is this sex-linked or autosomal? How can you tell? Sex linked, but could be autosomal
Genotypes - Can individual II, 4 be homozygous? Why or why not?
No, she must be heterozygous (receives recessive allele from dad).
5. Why do mothers of affected males often feel guilty?
Moms can be carriers and pass on trait to boys.
6. Which individual has a genotype/phenotype that is not possible for sex-linked traits?
Patterns of Inheritance
Autosomal Recessive
2. Autosomal Dominant
3. Sex-Linked (X-Linked)
1.
Autosomal Recessive Pedigree
Examples:
Sickle Cell Anemia,
Cystic Fibrosis,
Albinism,
Autosomal Recessive Pedigree
I
II
III
Sickle Cell
Anemia
Sickle Cell Anemia

A missense mutation is the cause of the disease,
sickle cell anemia.
◦ a change in one base pair alters one amino acid

effects hemoglobin protein, causing red blood
cells to take on a strange shape
◦ 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 (1 min)
Sickle Cell Tutorial (5 min)
Sickle Cell Disease


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.
Genetic Advantages


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


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
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.

Cystic Fibrosis


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


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.

Cystic Fibrosis (6:16)
Genetic Advantages




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.
Autosomal Dominant
Examples: Huntington’s Disease, Achondroplasia, Polydactyly
Autosomal Dominant Pedigree
I
II
III
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.


The symptoms of Huntington’s disease




Despite intensive study, the reason why these long strings of glutamine cause
disease is still not clear.
progressive breakdown (degeneration) of nerve cells in the brain
broad impact on a person's functional abilities and usually results in
movement, thinking (cognitive) and psychiatric disorders namely mental
deterioration and uncontrollable movements
usually does not appear until middle age.
The greater the number of codon repeats, the earlier the disease
appears, and the more severe are its symptoms.
Huntington's Disease - CA Stem Cell Agency (3:50)
Achondroplasia
a skeletal disorder, which is
characterized by the failure of
normal conversion of cartilage into
bone that begins during fetal life
and causes dwarfism.
 About 80 percent of people with
achondroplasia have average-size
parents; these cases result from
new mutations in the FGFR3 gene.
Achondroplasia (2:39)

Polydactyly

a condition in which a person has more
than five fingers per hand or five toes per
foot
Sex-Linked Pedigree
Examples: Colorblindness, Hemophilia, Muscular Dystrophy
Sex-Linked Pedigree
I
II
III
Sex-Linked Pedigree