Biology – Premed
Windsor University School of
Medicine and Health Sciences
DR. UCHE AMAEFUNA
THERE
ARE MORE
TO LECTURES THAN
SLIDES………
Pre Med – Biology Genetic Review
Autosomal Dominant, Autosomal Recessive
& Sex-linked Disorders and Pedigrees
There is more to lectures than the
power point slides!
Engage your mind
What is the difference between an
Autosome and a Sex-chromosome?

Autosomes are the first 22
homologous pairs of human
chromosomes that do not
influence the sex of an
individual.

Sex Chromosomes are the
23rd pair of chromosomes that
determine the sex of an
individual.
Autosomal Traits
 Genes
located on Autosomes control
Autosomal traits and disorders.
2 Types of Traits:
 Autosomal Dominant
 Autosomal Recessive
Autosomal Dominant Traits

If dominant allele is present on the autosome, then the
individual will express the trait.

A = dominant a = recessive

What would be the genotype of an individual with an
autosomal dominant trait?


AA and Aa (Heterozygotes are affected)
What would be the genotype of an individual without the
autosomal dominant trait?

aa
Autosomal Recessive Traits

If dominant allele is present on the autosome, then the
individual will not express the trait. In order to express
the trait, two recessive alleles must be present.

A = dominant a = recessive

What would be the genotype of an individual with an
autosomal recessive trait?


aa
What would be the genotype of an individual without the
autosomal recessive trait?


AA or Aa
Aa – called a Carrier because they carry the recessive allele and
can pass it on to offspring, but they do not express the trait.
Sex-Linked Traits


Sex-linked traits are produced by genes only on the X
chromosome.
They can be Dominant or Recessive.

A = dominant a = recessive

What would be the genotypes of a male and female that have a Sexlinked Dominant trait and do not express the trait?
Expresses Trait:
Male - XA Y
Female - XA XA or XA Xa
No Expression:
Male - Xa Y
Female - Xa Xa






What would be the genotypes of a male and female that have a Sexlinked Recessive trait and do not express the trait?
Expresses Trait:
Male - Xa Y
Female - Xa Xa
No Expression:
Male - XA Y
Female - XA XA or XA Xa
(Carrier)
Most Sex-linked traits are Recessive!
Genetic Counselor Activity

Imagine that you are a Genetic
Counselor assigned to family
to discuss with them the
possibility of their child
inheriting a genetic disorder.

You are given the family history and
whether or not the disorder is
Autosomal Dominant or Autosomal
Recessive.

Draw Punnett Squares to determine
odds of children inheriting the
disease and answer the questions
on the worksheet.
Punnett Square
If male & female are
heterozygous for eye
color
X
male
female
brown:
blue:
3/4 offspring
1/4 offspring
How to Construct a Pedigree?
A
Pedigree is a visual showing the pattern
of inheritance for a trait. (Family tree)
 Symbols
and Rules:
 Male =
Female =
 Affected =
Unaffected =
Carrier =
 Link parents together with a line and then
make a vertical line to connect to offspring.
Autosomal Dominant Pedigree
 Draw
a Pedigree showing a cross between
Heterozygous parents that have 2 boys
and 2 girls. (Show all possibilities)
Genotypes of Affected and Unaffected:
 AA and Aa = Affected
aa = Unaffected
Aa
aa
Aa
Aa
Aa
AA
Autosomal Recessive Pedigree
 Draw
a Pedigree showing a cross between
Heterozygous parents that have 2 boys
and 2 girls. (Show all possibilities)
Genotypes of Affected and Unaffected:
 AA=Unaffected Aa=Carrier, Unaffected
aa=Affected
Aa
aa
Aa
Aa
Aa
AA
Sex-Linked Recessive Pedigree

Draw a Pedigree showing a cross between a
Red eyed Male fruit fly and a Carrier Female fruit
fly which have 2 males and 2 females. (Show all
possibilities) Red is dominant to white.

Genotypes of Parents:
 Male = XR Y Female = XR Xr
XRY
XRY
XRXr
XrY
XRXR
XRXr
Characteristics of Autosomal Dominant,
Autosomal Recessive, and Sex-linked
Recessive Traits
 In
groups, analyze your notes on each
type of disorder and examine the
pedigrees.
 Come
up with rules/characteristics for
each type of Trait.
Autosomal Dominant Traits






Heterozygotes are affected
Affected children usually have affected parents.
Two affected parents can produce an unaffected
child. (Aa x Aa)
Two unaffected parents will not produce affected
children. (aa x aa)
Both males and females are affected with equal
frequency.
Pedigrees show no Carriers.
Autosomal Recessive Traits

Heterozygotes are Carriers with a normal phenotype.
 Most affected children have normal parents. (Aa x Aa)
 Two affected parents will always produce an affected
child. (aa x aa)
 Two unaffected parents will not produce affected
children unless both are Carriers. (AA x AA, AA x Aa)
 Affected individuals with homozygous unaffected mates
will have unaffected children. (aa x AA)
 Close relatives who reproduce are more likely to have
affected children.
 Both males and females are affected with equal
frequency.
 Pedigrees show both male and female carriers.
Sex-Linked Recessive Traits






More males than females are affected.
An affected son can have parents who have the
normal phenotype. (XAY x XAXa)
For a daughter to have the trait, her father must
also have it. Her mother must have it or be a
carrier.
(XaY, XaXa, XAXa)
The trait often skips a generation from the
grandfather to the grandson.
If a woman has the trait (XaXa), all of her sons
will be affected.
Pedigrees show only female carriers but no
male carriers.
Examples of Autosomal Dominant Disorders




Dwarfism
Polydactyly and Syndactyly
Hypertension
Hereditary Edema

Chronic Simple Glaucoma – Drainage system for fluid in the eye does not work and
pressure builds up, leading to damage of the optic nerve which can result in
blindness.
Huntington’s Disease – Nervous system degeneration resulting in certain and early
death. Onset in middle age.
Neurofibromatosis – Benign tumors in skin or deeper
Familial Hypercholesterolemia – High blood cholesterol and propensity for heart
disease
Progeria – Drastic premature aging, rare, die by age 13. Symptoms include limited
growth, alopecia, small face and jaw, wrinkled skin, atherosclerosis, and
cardiovascular problems but mental development not affected.




Examples of Autosomal Recessive Disorders






Congenital Deafness
Diabetes Mellitus
Sickle Cell anemia
Albinism
Phenylketoneuria (PKU) – Inability to break
down the amino acid phenylalanine.
Requires elimination of this amino acid from
the diet or results in serious mental
retardation.
Galactosemia – enlarged liver, kidney failure,
brain and eye damage because can’t digest
milk sugar
Cystic Fibrosis – affects mucus and sweat
glands, thick mucus in lungs and digestive
tract that interferes with gas exchange, lethal.
 Tay Sachs Disease – Nervous system
destruction due to lack of enzyme needed to
break down lipids necessary for normal brain
function. Early onset and common in
Ashkenazi Jews; results in blindness,
seizures, paralysis, and early death.

Examples of Sex-Linked Recessive Disorders







Red/Green Colorblindness – Difficulty perceiving
differences between colors (red or green, blue or yellow).
Hemophilia – Absence of one or more proteins necessary
for normal blood clotting.
Deafness
Cataracts – opacity in the lens that can lead to blindness
Night blindness – (Nyctalopia) rods do not work so that
can not see in the dark
Glaucoma – pressure in the eye that can lead to optic nerve
damage and blindness
Duchenne Muscular Dystrophy – progressive weakness
and degeneration of skeletal muscles that control movement
due to absence of dystrophin (protein that maintains muscle
integrity). Mainly in boys, onset 3-5 yrs, by 12 years can’t
walk, and later needs respirator.
Genetic Mutations:
Chromosomal
What are Chromosomal Mutations?
Damage to chromosomes due to
physical or chemical disturbances or
errors during meiosis.
Two Types of Chromosome Mutations:


1.
2.
Chromosome Structure
Chromosome Number
Problems with Chromosome Structure:
1.
2.
3.
4.
Deletion – during cell division, especially meiosis, a
piece of the chromosome breaks off, may be an end
piece or a middle piece (when two breaks in a
chromosome occur).
Inversion – a segment of the chromosome is turned
180°, same gene but opposite position
Translocation – movement of a chromosome segment
from one chromosome to a non-homologous
chromosome
Duplication – a doubling of a chromosome segment
because of attaching a broken piec form a homologous
chromosome, or by unequal crossing over.
Problems with Chromosome Number
5.
6.
7.
Monosomy – only one of a particular type
of chromosome (2n -1)
Trisomy – having three of a particular
type of chromosome (2n + 1)
Polyploidy – having more than two sets
of chromosomes; triploids (3n = 3 of
each type of chromosome), tetraploids
(4n = 4 of each type of chromosome).
How do you think Chromosomal
Mutations with differing number of
chromosomes develops?



Monosomy and Trisomy due to Nondisjunction –
members of homologous chromosomes do not
move apart in Meiosis I or sister chromatids do not
separate during Meiosis II leaves one cell with too
few chromosomes and one cell with too many.
Triploids develop from the fertilization of an
abnormal diploid egg, produced from the
nondisjunction of all chromosomes. Tetraploids
develop from the failure of a 2n zygote to divide
after replicating its chromosomes, subsequent
mitosis would produce 4n embryo.
Polyploidy is common in the plant kingdom,
spontaneous origin of polyploid individuals plays
important role in evolution of plants. In the animal
kingdom, natural occurrence of polyploids is
extremely rare. In general, polyploids are more
nearly normal in appearance than having
monosomy or trisomy, which is more disruptive to
have one extra chromosome in a pair.
Genotypes
Phenotypes
 At
each locus (except for sex chromosomes)
there are 2 genes. These constitute the
individual’s genotype at the locus.
 The
expression of a genotype is termed a
phenotype. For example, hair color, weight,
or the presence or absence of a disease.
27
Genotypes
Phenotypes (example)
genotypes
phenotypes
 Eb -
dominant allele.
 Ew- recessive allele.
28
Dominant vs. Recessive
A dominant allele is
expressed even if it is
paired with a recessive
allele.
A recessive allele is only
visible when paired with
another recessive allele.
29
Mendel’s 1st Law
Two members of a gene pair segregate from each other into
the gametes, so half the gametes carry one member of the
pair and the other half carry the other member of the pair.
Mendel’s 2nd Law

Different gene pairs assort independently
in gamete formation.
This “law” is true only in some cases.
Gene pairs on SEPARATE CHROMOSOMES
assort independently at meiosis.
30
X-linked Inheritance
Different results obtained
from reciprocal crosses
between red-eyed and whiteeyed Drosophila.
Explanation: The gene
responsible for eye-color
is X-linked. Females have
2 X-chromosomes, while
males have 1 X-chromosome
and 1 Y-chromosome.
31
Medical Genetics
When studying rare disorders, 6 general
patterns of inheritance are observed:

Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant
Codominant

Mitochondrial




32
Medical Genetics (cont.)
Autosomal recessive
 The disease appears
in male and female
children of
unaffected parents.
 e.g., cystic fibrosis
33
Medical Genetics (cont.)
Autosomal dominant
 Affected males and
females appear in each
generation of the
pedigree.
 Affected mothers and
fathers transmit the
phenotype to both sons
and daughters.
 e.g., Huntington disease.
34
Medical Genetics (cont.)
X-linked recessive
 Many more males than
females show the
disorder.
 All the daughters of an
affected male are
“carriers”.
 None of the sons of an
affected male show the
disorder or are carriers.
 e.g., hemophilia
35
Medical Genetics (cont.)
X-linked dominant
 Affected males pass the
disorder to all daughters
but to none of their sons.
 Affected heterozygous
females married to
unaffected males pass the
condition to half their
sons and daughters
 e.g. fragile X syndrome
36
Medical Genetics (cont.)
Co-dominant inheritance
Two different versions
(alleles) of a gene can be
expressed, and each
version makes a slightly
different protein
 Both alleles influence the
genetic trait or determine
the characteristics of the
genetic condition.
 E.g. ABO locus

37
Medical Genetics (cont.)
Mitochondrial inheritance
 This type of inheritance
applies to genes in
mitochondrial DNA
 Mitochondrial disorders can
appear in every generation
of a family and can affect
both males and females, but
fathers do not pass
mitochondrial traits to their
children.
 E.g. Leber's hereditary
optic neuropathy (LHON)
38
Question #1
1
2
Write the genotypes in every possible place.
If individuals 1 and 2 marry, what is the probability that
their first child will be sick?
39
Question #2

PKU is a human hereditary disease resulting from
inability of the body to process the Amino Acid
phenylalanine (contained in protein that we eat).

It is caused by a recessive allele with simple
Mendelian inheritance.

Some couple wants to have children. The man has
a sister with PKU and the woman has a brother
with PKU. There are no other known cases in their
families.

What is the probability that their first child
40
will have PKU ?
Question #2-Solution Highlights
P/p
P/p
P/p
P/p
p/p
P/-
P/-
p/p
P – the normal allele
p – the mutant allele
41
Question #3
The disease is rare.
1
2
3
4
5
6
7
8
9
10
a. What is the most likely mode of inheritance ?
b. What would be the outcomes of the cousin marriages
1 x 9, 1 x 4, 2 x 3, and 2 x 8 ?
42
Question #3-Solution Highlights
Observations:
a.


After the disease is introduced into the family in generation
#2, it appears in every generation  dominant!
Fathers do not transmit the phenotype to their sons 
X-linked!
The outcomes:
b.




1 x 9: 1 must be A/a
9 must be A/Y
1 x 4: 1 must be A/a
4 must be a/Y
2 x 3: 2 must be a/Y
3 must be A/a
2 x 8: 2 must be a/Y
8 must be a/a
Same
All normal
43
Notes
Cystic fibrosis – disease affecting the mucus
lining of the lungs, leading to breathing problems
and other difficulties
 Huntington disease - or Huntington's chorea is
an inherited disorder characterized by abnormal
body movements called chorea, and loss of
memory. There also is evidence that doctors as
far back as the Middle Ages knew of this
devastating disease. The incidence is 5 to 8 per
100,000. It takes its name from the New York
physician George Huntington who first described
it precisely in 1872.

44
Notes
Hemophilia-illness that impair the body's ability
to control bleeding.
 Fragile X syndrome - is a genetic condition that
causes a range of developmental problems
including learning disabilities and mental
retardation. Usually males are more severely
affected by this disorder than females. In
addition to learning difficulties, affected males
tend to be restless, fidgety, and inattentive.
Affected males also have characteristic physical
features that become more apparent with age.

45
Notes -cont
DNA - a pair of molecules joined by hydrogen
bonds: it is organized as two complementary
strands, head-to-toe, with the hydrogen bonds
between them. Each strand of DNA is a chain of
chemical "building blocks", called nucleotides, of
which there are four types:adenide (abbreviated
A), cytozyne (C), guanine (G) and thymine (T).
 Mitochondria, which are structures in each cell
that convert molecules into energy, each contain a
small amount of DNA.
 A chromatid forms one part of a chromosome after
it has coalesced for the process of mitosis or
meiosis. During either process, the word
"chromosome" indicates a pair of two exactly
identical ("sister") chromatids joined at the central
point of each chromatid, called the centromere.

46
Notes -cont
 Mitosis
is the process by which a cell
separates its duplicated genome into two
identical halves
 Meiosis is the process that transforms one
diploid into four haploid cells.
 Reciprocal cross a cross, with the
phenotype of each sex reversed as
compared with the original cross, to test
the role of parental sex on inheritance
pattern. A pair of crosses of the type
genotype A(female) X genotype B(male)
and genotype B(female) X genotype
A(male).
47
Genetic Disorders
What Are Mutations?
 Changes
in the
nucleotide sequence of
DNA
 May occur in somatic
cells (aren’t passed to
offspring)
 May occur in gametes
(eggs & sperm) and be
passed to offspring
Are Mutations Helpful or
Harmful?
 Mutations
happen
regularly
 Almost all mutations are
neutral
 Chemicals & UV
radiation cause
mutations
 Many mutations are
repaired by enzymes
Are Mutations Helpful or
Harmful?
 Some
type of skin
cancers and leukemia
result from somatic
mutations
 Some mutations may
improve an organism’s
survival (beneficial)
Types of Mutations
Chromosome Mutations
 May


Involve:
Changing the
structure of a
chromosome
The loss or
gain of part of a
chromosome
 Five
Chromosome
Mutations
types exist:
 Deletion
 Inversion
 Translocation
 Nondisjunction
 Duplication
Deletion
 Due
to breakage
 A piece of a
chromosome is lost
Inversion
 Chromosome
segment
breaks off
 Segment flips around
backwards
 Segment reattaches
Duplication
 Occurs
when a
gene sequence is
repeated
Translocation
 Involves
two
chromosomes that
aren’t homologous
 Part of one
chromosome is
transferred to
another chromosomes
Translocation
Nondisjunction
 Failure
of chromosomes to
separate during meiosis
 Causes gamete to have too many
or too few chromosomes
 Disorders:



Down Syndrome – three 21st
chromosomes
Turner Syndrome – single X chromosome
Klinefelter’s Syndrome – XXY
chromosomes
Chromosome Mutation
Animation
Gene Mutations
 Change
in the
nucleotide sequence
of a gene
 May only involve a
single nucleotide
 May be due to
copying errors,
chemicals, viruses,
etc.
Types of Gene Mutations
 Include:
Point Mutations
 Substitutions
 Insertions
 Deletions
 Frameshift

Point Mutation
 Change
of a single
nucleotide
 Includes the deletion,
insertion, or
substitution of ONE
nucleotide in a gene
Point Mutation
 Sickle
Cell
disease is the
result of one
nucleotide
substitution
 Occurs in the
hemoglobin gene
Frameshift Mutation
 Inserting
or deleting
one or more
nucleotides
 Changes the “reading
frame” like changing a
sentence
 Proteins built
incorrectly
Frameshift Mutation
 Original:
The fat cat ate the wee
rat.
 Frame Shift (“a” added):
 The fat caa tet hew eer
at.

Amino Acid Sequence
Changed
Mutations

Gene mutations can be either inherited
from a parent or acquired. A hereditary
mutation is a mistake that is present in the
DNA of virtually all body cells. Hereditary
mutations are also called germ line
mutations because the gene change exists
in the reproductive cells and can be passed
from generation to generation, from parent
to newborn. Moreover, the mutation is
copied every time body cells divide
 Mutations
occur all the time in every cell in
the body. Each cell, however, has the
remarkable ability to recognize mistakes
and fix them before it passes them along
to its descendants. But a cell's DNA repair
mechanisms can fail, or be overwhelmed,
or become less efficient with age. Over
time, mistakes can accumulate.
Nondisjunction
n+1
n+1
n-1
chromosome
alignments at
metaphase I
n-1
nondisjunction alignments at
at anaphase I metaphase II
anaphase II
Down’s Syndrome

Caused by nondisjunction of the
21st chromosome.
 This means that the
individual has a
trisomy (3 – 2lst
chromosomes).
Down’s Syndrome or Trisomy 21
Symptoms of Down Syndrome

Upward slant to eyes.
 Small ears that fold over at the top.
 Small, flattened nose.
 Small mouth, making tongue appear large.
 Short neck.
 Small hands with short fingers.
Symptoms of Down Syndrome






Low muscle tone.
Single deep crease across center of palm.
Looseness of joints.
Small skin folds at the inner corners of the eyes.
Excessive space between first and second toe.
In addition, down syndrome always involves
some degree of mental retardation, from mild to
severe. In most cases, the mental retardation is
mild to moderate.
Kleinfelter’s syndrome
(or Klinefleter’s)
 Disorder
occurring due to nondisjunction
of the X chromosome.
 The Sperm containing both X and Y
combines with an egg containing the X,
results in a male child.
 The egg may contribute the extra X
chromosome.
XXY

Males with some development of breast
tissue normally seen in females.
 Little body hair is present, and such person
are typically tall, have small testes.
 Infertility results from absent sperm.

Evidence of mental retardation may or may
not be present.
 Klinefleter’s
Turner’s




Turner syndrome is associated
with underdeveloped ovaries,
short stature, webbed, and is
only in women.
Bull neck, and broad chest.
Individuals are sterile, and lack
expected secondary sexual
characteristics.
Mental retardation typically
not evident.
Chromosomal or monogenic?
Turner’s Syndrome
Sickle Cell Anemia

An inherited, chronic
disease in which the red
blood cells, normally
disc-shaped, become
crescent shaped. As a
result, they function
abnormally and cause
small blood clots. These
clots give rise to
recurrent painful
episodes called "sickle
cell pain crises".
Sickle Cell
 Sickle
cell disease is most commonly
found in African American populations.
 This disease was discovered over 80
years ago, but has not been given the
attention it deserves.
Cystic Fibrosis (CF)
 Monogenic
 Cause:
deletion of only 3 bases on
chromosome 7
 Fluid in lungs, potential respiratory failure
 Common among Caucasians…1 in 20 are
carriers

Therefore is it dominant or recessive?
Tay-Sachs disease
 Monogenic,
autosomal recessive
 Central nervous system degrades,
ultimately causing death.
 Most common among people of Jewish,
eastern Europe descent.
Muscular Dystrophy

What Is Muscular Dystrophy?
Muscular dystrophy is a disease in which the
muscles of the body get weaker and weaker and
slowly stop working because of a lack of a
certain protein (see the relationship to
genetics?)
 Can be passed on by one or both parents,
depending on the form of MD (therefore is
autosomal dominant and recessive)
Hemophilia, the royal disease




Hemophilia is the oldest
known hereditary
bleeding disorder.
Caused by a recessive
gene on the X
chromosome.
There are about 20,000
hemophilia patients in the
United States.
One can bleed to death
with small cuts.

The severity of
hemophilia is related to
the amount of the clotting
factor in the blood. About
70% of hemophilia
patients have less than
one percent of the normal
amount and, thus, have
severe hemophilia.
X-linked Inheritance pedigree
chart
Huntington’s Disease

Huntington's disease (HD)
is an inherited,
degenerative brain
disorder which results in
an eventual loss of both
mental and physical
control. The disease is
also known as
Huntington's chorea.
Chorea means "dance-like
movements" and refers to
the uncontrolled motions
often associated with the
disease.
Huntington’s

Looking back at the
pedigree chart is
Huntington’s dominant or
recessive?

Scientists have discovered
that the abnormal protein
produced by the
Huntington's disease gene,
which contains an elongated
stretch of amino acids
called glutamines, binds
more tightly to HAP-1 than
the normal protein does.
Phenylketonuria or
PKU
People with PKU cannot consume any product that
contains aspartame.
PKU is a metabolic disorder that results when the
PKU gene is inherited from both parents
(recessive or dominant?)
Caused by a deficiency of an enzyme which is
necessary for proper metabolism of an amino
acid called phenylalanine.
PKU
 Phenylalanine
is an essential amino
acid and is found in nearly all foods
which contain protein, dairy products,
nuts, beans, tofu… etc.
 A low protein diet must be followed.
 Brain damage can result if the diet is not
followed causing mental
retardation…and mousy body odor
(phenylacetic acid is in sweat).
PKU
Phenylalanine.
Free diet

ALS
(Amyotrophic Lateral Sclerosis,
or Lou Gehrig’s disease)

the disease strikes people between the
ages of 40 and 70, and as many as
30,000 Americans have the disease at
any given time
 This monogenic mutation is believed to
make a defective protein that is toxic to
motor nerve cells.
 A common first symptom is a painless
weakness in a hand, foot, arm or leg,
other early symptoms include speech
swallowing or walking difficulty
Adenoleukodystrophy (ALD)

ALD is a rare, inherited metabolic
disorder that afflicts the young boy
Lorenzo Odone, whose story is
told in the 1993 film 'Lorenzo's oil'.
In this disease the fatty covering
(myelin sheath) on nerve fibers in
the brain is lost, and the adrenal
gland degenerates, leading to
progressive neurological disability
and death.
Diabetes
 Disease
in which the body does
not produce or properly use insulin.

Insulin is a hormone that is needed to convert
sugar, starches, and other food into energy
needed for daily life.
 Genetic
mutation can lead to Type 1
diabetes, but no one sure if relative to a
specific gene
Diabetes

Type 1 reveals itself in childhood, Type 2 can be
made worse from excessive lifestyle

Warning signs






Extreme thirst
Blurry vision from time to time
Frequent urination
Unusual fatigue or drowsiness
Unexplained weight loss
Diabetes is the leading cause of kidney
failure, blindness, and amputation in
adults, and can also lead to heart disease.
Color Blindness

Cause: x-linked
recessive
 1/10 males have,
1/100 females have.
Why the difference?
 Individuals are
unable to distinguish
shades of redgreen.
 Are you color blind?
Albinism
 Patients
are unable to produce skin or eye
pigments, and thus are light-sensitive
 Autosomal recessive
Genetic Screening
 Large-scale
screening programs detect
affected persons
 Newborns
in United States routinely
tested for PKU

Early detection allows dietary intervention
and prevents brain impairment
Prenatal Diagnosis

Amniocentesis

Chorionic villus sampling

Fetoscopy

All methods have some risks
Prenatal Diagnosis
Amniocentesis
Chorionic villus sampling
The Genetic Code
The Genetic Code: How many code words (codons)?
[43 = 64 codons of 3 bases each (all are used)]
Arg = CG(N)
(Start) AUG
Genetic Code
 Consists
of a triplet
code

That is, a sequence of
three bases codes for
a particular amino acid.
are 43, or 64
possible combinations
 A group of 3 bases
coding for an amino
acid in mRNA is called
a codon
 There
Genetic Code
 Degenerate: an amino acid
can be coded for by more
than one codon
 Unambiguous: each condon
indicates a single, specific
amino acid
 Non-overlapping: when
translated, the "reading
frame" is advanced 3 bases
at a time
 61 codons are for amino
acids, and the remaining
three are "stop codons" that
terminate the polypeptide
ATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAACATGTTATTCA
ACAAAAAGATTTGGACTGTAACTTAAAAATGATCAAATTATGTTTCCCATGCATCAGGTGC
GGGAAGCTCTTCTGGAGAGTGAGAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGT
GAAAGATGAGGAAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATG
GAATGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTGTACAG
CTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAATTAAGTGTGGCAGGAATG
TGTAGACACAGTAATTTGCTTGTATGGAATTTTGCCTGAGAGACCTCATTGCAGTTTCTG
TTTTGATGTCTTCATCCATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCAC
AACCCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCACAGTTATCC
TTTTATGAATGGAGTTheGeneticBasisofHumanVariationGATGAAAACCTTAGGAATAATG
GATTTGCGCAGGCTCACCTGGATATTAAGACTGAGTCAAATGTTGGGTCTGGTCTGACT
ATGTTTGCTTTGTTCATGAGCACCACATATTGCCTCTCCTATGCAGTTAAGCAGGTAGGT
AGAAAAGCCCATGTTTGTCTCTACTCACACACTTCCGACTGAATGTATGTATGGAGTTTC
ACCAGATTCTTCAGTGCTCTGGATATTAACTGGGTATCCCATGACTTTATTCTGACACTAC
GGACCTTGTCAAATAGTTTGGACCTTGTCAAATAGTTTGGAGTCCTTGTCAAATAGTTTG
GTTAGCACAGACCCCACAAGTTAGGGGCTCAGTCCCACGAGGCCATCCTCACTTCAGAT
AATGGCAAGTCCTAAGTTGTCACCATACTTTTGACCAACCTGTTACCAATCGGGGGTTC
GTAACTGTCTTCTTGGGTTTAATAATTTGCTAGAACAGTTTACGGAACTCAGAAAAACAGT
TTTTCTTTTTTTCTGAGAGAGAGGGTCTTATTTTGTTGCCCAGGCTGGTGTGCAATGGTG
GTCATAGCTCATTGCAGCCTTGATTGTCTGGGTTCCAGTGGTTCTCCCACCTCAGCCTCC
GTAGCTGAGACTACATGCCTGCACCACCACATCTGGCTAGTTTCTTTTATTTTTTGTATAG
GGGTCTTGTTGTGTTGGCCAGGCTGGCCACAAATTCCTGGTCTCAAGTGATCCTCCCA
CAGCCTCTGAAAGTGCTGGGATTACAGATGTGAGCCACCACATCTGGCCAGTTCATTTC
TTACTGGTTCATTGTGAAGGATACATCTCAGAAACAGTCAATGAAAGAGACGTGCATGCT
ATGCAGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCAAGGTGGGAGGATCGCT
Whose genome was sequenced?
International Human Genome
Sequencing Consortium
The human genome reference sequence
does not represent an exact match for
any one person's genome.
The draft genome is composed of the
DNA of an estimated 10 to 20
anonymous individuals across different
racial and ethnic groups.
The Genetic Basis for Human Variation
Class of variation
Rules for assigning allele to class
Example
Frequency
Single Nucleotide
Polymorphism (SNP)
Single base substitution involving A,T,C, or A/T
G
5,692,700
(~93%)
Deletion/Insertion
Polymorphisms (DIPs)
Designated using the full sequence of the
insertion as one allele, and either a fully
defined string for the variant allele or a “-”
character to specify the
deleted allele.
T/-CCTA/G
431,319
(~7%)
Microsatellite or short
tandem repeat (STR)
Alleles are designated by providing the
repeat motif and the copy number for each
allele.
(CAC)8/9/10/11
2,440
(0.04%)
Named variant
Applies to insertion/deletion
polymorphisms of longer sequence
features, such as retroposon dimorphism
.for Alu or line elements
(alu) / -
1,859
(0.03%)
Any 2 human genomes are roughly 99.9% identic
Chr - chromosome
n - Number of samples examined
bp - Number of basepairs sequences
S - Number of polymorphic sites
p - Nucleotide divergence
On average ~ 0.1%
Przeworski, M., et al. (2000) Trends Genet 16, 296-302.
Molecular
Biology of
Inheritance
DNA Is the Genetic Material
10-118
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
DNA is a transforming substance
 During
the late 1920s, the bacteriologist
Frederick Griffith was attempting to
develop a vaccine against Streptococcus
pneumoniae (pneumococcus)
Griffith’s transformation experiment
10-119
DNA, not protein, is the genetic material

Hershey and Chase Experiment

In their experiment, Hershey and Chase relied on a chemical
difference between DNA and protein to solve whether DNA or
protein was the genetic material
Structure of the virus (T2
bacteriophage) used by
Hershey and Chase
10-120
Hershey and Chase experiment I
10-121
Hershey and Chase experiment II
10-122
DNA and RNA are polymers of nucleotides
 Nucleic
acids contain only nucleotides,
molecules that are composed of a
nitrogen-containing base, a phosphate,
and a pentose
(5-carbon sugar)
 DNA (deoxyribonucleic acid) contains
the
5-carbon sugar deoxyribose
 DNA contains four nucleotides with
different bases

10-123
Adenine, Guanine, Thymine, and Cytosine
DNA is a polynucleotide—contains many nucleotides
10-124
The four bases in DNA nucleotides
10-125
RNA


RNA (ribonucleic acid) another polymer of nucleotides
RNA differs from DNA


Has ribose as a sugar, not deoxyribose
Has uracil in place of thymine
The uracil
nucleotide in RNA
replaces thymine
in DNA
10-126
DNA meets the criteria for the genetic
material
 The



genetic material must be:
Variable between species and able to store
information that causes species to vary from
one another
Constant within a species and able to be
replicated with high fidelity during cell division
Able to undergo rare changes, called
mutations, that provide the genetic variability
that allows evolution to occur
10-127
Complementary base pairing
10-128
DNA is a Double Helix

The double helix suggests that the stability and variability
of the molecule is in the sequence of bases
X-ray diffraction of DNA
10-129
The Watson and Crick model of DNA
10-130
DNA replication is semi-conservative
 DNA
replication - the process of copying a
DNA molecule
 Replication requires the following steps:



Unwinding: Old strands are unwound and
“unzipped”
Complementary base pairing: New
complementary nucleotides are positioned by the
process of base pairing
Joining: Complementary nucleotides join to form
new strands
• Each daughter DNA molecule contains a template
strand, or old strand, and a new strand
 Steps
2 and 3 are carried out by DNA
polymerase
10-131
Semi-conservative
replication (simplified)
10-132
Many different proteins help DNA replicate
DNA replication (in depth)
10-133
Genes are linked to proteins
Chemical basis of sickle-cell
disease in humans
10-134
The making of a protein requires
transcription and translation
 Gene
- segment of DNA that specifies the
amino acid sequence of a protein
 During transcription DNA serves as a
template for RNA formation

DNA is transcribed, monomer by monomer,
into RNA
 During
translation an RNA transcript
directs the sequence of amino acids in a
polypeptide
10-135
Genetic code

1966
 The Genetic code
was discovered;
scientists are now
able to predict
characteristics by
studying DNA. This
leads to genetic
engineering, genetic
counseling.
Overview of gene expression
10-137
The genetic code for amino acids is a triplet
code
 Genetic
code - sequence of nucleotides
in DNA specifies the order of amino acids
in a polypeptide

Codon - three base sequence corresponding
to a specific amino acid
 Important



properties of the genetic code:
The genetic code is degenerate
The genetic code is unambiguous
The code has start and stop signals
10-138
RNA Codons
10-139
During transcription, a gene passes its coded
information to an mRNA
 messenger
RNA (mRNA) - takes instructions
from DNA in the nucleus to the ribosomes in the
cytoplasm
 RNA polymerase joins the nucleotides
together

Promoter defines the start of a gene, the direction
of transcription, and the strand to be transcribed
 Stop
sequence causes RNA polymerase to stop
transcribing the DNA and to release the mRNA
molecule, called an mRNA transcript
10-140
Transcription:
synthesis of RNA
10-141
In eukaryotes, an mRNA is processed before
leaving the nucleus
 Primary
mRNA is composed of exons and
introns

The exons of mRNA will be expressed, but the
introns will not
 Function


of Introns
Might allow exons to be put together in different
sequences so that various mRNAs and proteins
can result from a single gene
Some introns might regulate gene expression by
feeding back to determine which coding genes
are to be expressed and how they should be
spliced
10-142
During translation, each transfer RNA carries a
particular amino acid
 transfer
RNA (tRNA) molecules transfer
amino acids to the ribosomes

Anticodon - a group of three bases that is
complementary to a specific codon of mRNA
at a ribosome
 Wobble
hypothesis - the first two
positions in a tRNA anticodon pair obey
the A–U/G–C configuration, but the third
position can be variable

Helps ensure that, despite changes in DNA
base sequences, the correct sequence of
amino acids will result in a protein
10-143
Cloverleaf
model
of tRNA
10-144
Space-filling model of tRNA molecule
10-145
Translation occurs at ribosomes in
cytoplasm
 ribosomal
RNA (rRNA) is produced from
a DNA template in the nucleolus of a
nucleus
 Polyribosome - several ribosomes are
often attached to and translating the same
mRNA
10-146
Ribosome structure and function
10-147
10.15 Initiation begins the process
of polypeptide production

Initiation - the step that brings all the translation
components together
Figure 10.15 Initiation
10-148
Elongation builds a polypeptide
one amino acid at a time

Elongation - a polypeptide increases in length one
amino acid at a time
Elongation cycle
10-149
Let’s review gene expression
10-150
10-151
Mutations affect genetic information and
expression
 Genetic
mutation - a permanent change
in the sequence of bases in DNA


Point mutations - a change in a single DNA
nucleotide and, therefore, a change in a
specific codon
Frameshift mutations occur when one or
more nucleotides are either inserted or
deleted from DNA
10-152
Types of point mutations
10-153
Many agents can cause mutations
 Some
mutations are spontaneous while
others are due to environmental mutagens
 Environmental Mutagens


Mutagen - an environmental agent that
increases the chances of a mutation
Carcinogens - cancer-causing agents
• Tobacco smoke contains a number of organic
chemicals that are known carcinogens
10-154
Transposons are “jumping genes”
 Transposons




have the following effects:
Are involved in transcriptional control because
they block transcription
Can carry a copy of host genes when they
jump and can be a source of chromosomal
mutations such as translocations, deletions,
and inversions
Can leave copies of themselves and certain
host genes before jumping and be a source of
duplication
10-155
Can contain one or more genes that make a
Connecting the Concepts

Using all previously collected data concerning DNA structure,
Watson and Crick were able to arrive at the legendary design of
DNA—a double helix

Complementary base pairing explains the replication of DNA,
how RNA molecules are made

Geneticists have confirmed that proteins are the link between
the genotype and the phenotype
DNA base sequence → amino acid sequence → enzyme → organism
structure
10-156