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• 11.1 Gregor Mendel
• 11.2 Mendel’s Laws
• 11.3 Mendelian Patterns of
Inheritance and Human Disease
• 11.4 Beyond Mendelian Inheritance
1
Phenylketonuria: A Human
Genetic Disorder
• Phenylalanine is an amino acid found in
many foods.
• Phenylketonurics are people who lack the
enzyme that breaks down phenylalanine.
 Excess phenylalanine accumulates in their
bodies, causing nervous system disorders.
 Phenylketonuria is a recessively inherited
trait, which means people have to inherit two
copies of the gene to have the disorder.
• Food labels inform phenylketonurics which foods
they should avoid.
2
11.1 Gregor Mendel
• The Blending Concept of Inheritance:
 Parents of contrasting appearance produce
offspring of intermediate appearance.
• Over time, variation would decrease as individuals
became more alike in their traits.
 Blending was a popular concept during Mendel’s
time.
• Mendel’s findings were in contrast with this.
 He formulated the particulate theory of inheritance.
 Mendel proposed the laws of segregation and
independent assortment.
• Inheritance involves reshuffling of genes from generation
3
to generation.
Gregor Mendel
• Austrian monk
 Studied science and mathematics at the University of
Vienna
 Conducted breeding experiments with the garden pea
Pisum sativum
 Carefully gathered and documented mathematical
data from his experiments
• Formulated fundamental laws of heredity in the
early 1860s
 Had no knowledge of cells or chromosomes
 Did not have a microscope
 Experiments on the inheritance of simple traits in the
garden pea disproved the blending hypothesis
4
Gregor Mendel
5
Mendel Worked with the
Garden Pea
• The garden pea:
 Organism used in Mendel’s experiments
 A good choice for several reasons:
• Easy to cultivate
• Short generation
• Normally self-pollinating, but can be crosspollinated by hand
– Pollen was transferred from the male (anther) of one plant
to the female (stigma) parts of another plant.
• True-breeding varieties available
• Simple, objective traits
6
Garden Pea Anatomy
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Flower Structure
stamen
anther
filament
stigma
style
ovules in
ovary
carpel
a.
7
Garden Pea Anatomy
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Cutting away
anthers
Brushing
on pollen
from another
plant
All peas are yellow when
one parent produces yellow
seeds and the other parent
produces green seeds.
8
11.2 Mendel’s Laws
• Mendel performed cross-breeding
experiments.
 Used “true-breeding” (homozygous) plants
 Chose varieties that differed in only one trait
(monohybrid cross)
 Performed reciprocal crosses
• Parental generation = P
• First filial generation offspring = F1
• Second filial generation offspring = F2
 Formulated the law of segregation
9
Monohybrid Cross Done by Mendel
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P generation
TT
tt
t
T
P gametes
F1 generation
Tt
eggs
F1 gametes
T
t
F2 generation
sperm
T
TT
Tt
Tt
tt
t
Offspring
Allele Key
T = tall plant
t = short plant
Phenotypic Ratio
3
1
tall
short
10
Mendel’s Laws
• Law of Segregation:
 Each individual has a pair of factors (alleles) for each
trait.
 The factors (alleles) segregate (separate) during
gamete (sperm & egg) formation.
 Each gamete contains only one factor (allele) from each
pair of factors.
 Fertilization gives the offspring two factors for each trait.
 Results of the monohybrid cross: All F1 plants were tall,
disproved blending hypothesis.
11
Mendel’s Laws
• Classical Genetics and Mendel’s Cross:
 Each trait in a pea plant is controlled by two alleles
(alternate forms of a gene).
 Dominant allele (capital letter) masks the expression
of the recessive allele (lowercase).
 Alleles occur on a homologous pair of chromosomes
at a particular gene locus.
• Homozygous = identical alleles
• Heterozygous = different alleles
12
Homologous Chromosomes
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sister chromatids
alleles at a
gene locus
a. Homologous
chromosomes
have alleles for
same genes at
specific loci.
G
g
R
r
S
s
t
T
G
Replication
b. Sister chromatids
of duplicated
chromosomes
have same alleles
for each gene.
R
G
g
g
R
r
r
S
S
s
s
t
t
T
T
13
Relationship Between Observed
Phenotype and F2 Offspring
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Trait
F2Results
Characteristics
Dominant
Recessive
Dominant
Recessive
Ratio
Tall
Short
787
277
2.84:1
Pod shape
Inflated
Constricted
882
299
2.95:1
Seed shape
Round
Wrinkled
5,474
1,850
2.96:1
Seed color
Yellow
Green
6,022
2,001
3.01:1
Axial
Terminal
651
207
3.14:1
Flower color
Purple
White
705
224
3.15:1
Pod color
Green
Yellow
428
152
2.82:1
14,949
5,010
2.98:1
Stem length
Flower position
Totals:
Mendel’s Laws
• Genotype
 It refers to the two alleles an individual has for a
specific trait.
 If identical, genotype is homozygous.
 If different, genotype is heterozygous.
• Phenotype
 It refers to the physical appearance of the individual.
15
Mendel’s Cross Viewed by
Modern Genetics
• The dominant and recessive alleles represent DNA
sequences that code for proteins.
• The dominant allele codes for the protein associated with
the normal gene function within the cell.
• The recessive allele represents a “loss of function.”
• During meiosis I the homologous chromosomes
separate.
 The two alleles separate from each other.
• The process of meiosis explains Mendel’s law of
segregation and why only one allele for each trait is in a
gamete.
16
Mendel’s Laws
• A dihybrid cross uses true-breeding plants differing in two traits.
• Mendel tracked each trait through two generations.




It started with true-breeding plants differing in two traits.
The F1 plants showed both dominant characteristics.
F1 plants self-pollinated.
He observed phenotypes among F2 plants.
• Mendel formulated the law of independent assortment.
 The pair of factors for one trait segregate independently of the factors
for other traits.
 All possible combinations of factors can occur in the gametes.
• P generation is the parental generation in a breeding experiment.
• F1 generation is the first-generation offspring in a breeding
experiment.
• F2 generation is the second-generation offspring in a breeding
experiment.
17
Dihybrid Cross Done by Mendel
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×
P generation
TTGG
P gametes
ttgg
tg
TG
F1 generation
TtGg
eggs
TG
F1 gametes
Tg
tG
tg
TG
TTGg
TtGG
TtGg
TTGg
TTgg
TtGg
Ttgg
TtGG
TtGg
ttGG
ttGg
TtGg
Ttgg
ttGg
ttgg
Tg
sperm
F2 generation
TTGG
tG
tg
Offspring
Allele Key
T
t
G
g
=
=
=
=
tall plant
short plant
green pod
Yellow pod
9
3
3
1
Phenotypic Ratio
tall plant, green pod
tall plant, yellow pod
short plant, green pod
short plant, yellow pod
Independent Assortment and
Segregation during Meiosis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
A
B
A
A
B
B
AB
A
B
A
Aa
a
B
Bb
b
a
a
a
b
b
b
ab
a
b
A
a
B
b
A
A
A
b
b
b
Ab
A
Parent cell has two
pairs of homologous
chromosomes.
A
Aa
a
b
bB
B
a
a
B
B
a
b
B
aB
a
B
All orientations of homologous chromosomes
are possible at
metaphase I in keeping
with the law of
Independent assortment.
At metaphase II, each
daughter cell has only
one member of each
homologous pair in
keeping with the law of
segregation
All possible combi tions of chromosomes
and alleles occur in
the gametes as
suggested by Mendel's
two laws.
19
Mendel’s Laws
• Punnett Square
 Table listing all possible genotypes resulting
from a cross
• All possible sperm genotypes are lined up on one
side.
• All possible egg genotypes are lined up on the
other side.
• All possible zygote genotypes are placed within the
20
squares.
Mendel and the Laws of
Probability
• Punnett Square
 It allows us to easily calculate probability of
genotypes and phenotypes among the offspring.
 Punnett square in next slide shows a 50% (or ½)
chance.
• The chance of E = ½
• The chance of e = ½
 An offspring will inherit:
•
•
•
•
The chance of EE = ½  ½ = ¼
The chance of Ee = ½  ½ = ¼
The chance of eE = ½  ½ = ¼
The chance of ee = ½  ½ = ¼
 The sum rule allows us to add the genotypes that
produce the identical phenotype to find out the
chance of a particular phenotype.
21
Punnett Square
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Parents
Ee
Ee
eggs
e
spem
E
EE
Ee
Ee
ee
e
Punnett square
E
Offspring
Allele key
E = unattached earlobes
e = attached earlobes
Phenotypic Ratio
3
1
unattached earlobes
attached earlobes
22
Mendel’s Laws
• Testcrosses
 Individuals with recessive phenotype always have the
homozygous recessive genotype.
 However, individuals with dominant phenotype have
indeterminate genotype.
• May be homozygous dominant, or
• Heterozygous
 A testcross determines the genotype of an individual
having the dominant phenotype.
23
One-Trait Testcrosses
24
Mendel’s Laws
• Two-trait testcross:
 An individual with both dominant phenotypes is
crossed with an individual with both recessive
phenotypes.
 If the individual with the dominant phenotypes
is heterozygous for both traits, the expected
phenotypic ration is 1:1:1:1.
25
11.3 Mendelian Patterns of
Inheritance and Human Disease
• Genetic disorders are medical conditions caused by
alleles inherited from parents.
• Autosome is any chromosome other than a sex
chromosome (X or Y).
• Genetic disorders caused by genes on autosomes are
called autosomal disorders.
 Some genetic disorders are autosomal dominant.
• An individual with AA has the disorder.
• An individual with Aa has the disorder.
• An individual with aa does NOT have the disorder.
 Other genetic disorders are autosomal recessive.
• An individual with AA does NOT have the disorder.
• An individual with Aa does NOT have the disorder, but is a carrier.
• An individual with aa DOES have the disorder.
26
Autosomal Recessive Pedigree
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Generations
I
aa
II
III
IV
A?
Aa
A?
Aa
A?
*
Aa
Aa
aa
aa
A?
A?
A?
Key
aa = affected
Aa = carrier (unaffected)
AA = unaffected
A? = unaffected
(one allele unknown)
Autosomal recessive disorders
• Most affected children have unaffected
parents.
• Heterozygotes (Aa) have an unaffected phenotype.
• Two affected parents will always have affected children.
• Close relatives who reproduce are more likely to have
affected children.
• Both males and females are affected with equal frequency.
27
Autosomal Dominant Pedigree
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Generations
Aa
Aa
I
*
II
III
Aa
aa
Aa
Aa
aa
A?
aa
aa
aa
aa
aa
aa
Key
AA = affected
Aa = affected
Autosomal dominant disorders
A? = affected
(one allele unknown)
• Affected children will usually have an
aa = unaffected
affected parent.
• Heterozygotes (Aa) are affected.
• Two affected parents can produce an unaffected child.
• Two unaffected parents will not have affected children.
• Both males and females are affected with equal frequency.
28
Mendelian Patterns of Inheritance
and Human Disease
• Autosomal Recessive Patterns of Inheritance
and Disorders:
 If both parents carry one copy of a recessive gene
they are unaffected but are capable of having a
child with two copies of the gene who is affected.
 Methemoglobinemia
• It is a relatively harmless disorder.
• Accumulation of methemoglobin in the blood causes
skin to appear bluish-purple.
 Cystic Fibrosis
• Mucus in bronchial tubes and pancreatic ducts is
particularly thick and viscous.
29
Methemoglobinemia
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
© Division of Medical Toxicology, University of Virginia
30
Cystic Fibrosis
31
Mendelian Patterns of
Inheritance and Human Disease
• Autosomal Dominant Patterns of Inheritance
and Disorders
• Two parents with a dominantly inherited disorder will
be affected by one copy of the gene.
• It is possible for them to have unaffected children.
 Osteogenesis Imperfecta
• Characterized by weakened, brittle bones.
• Most cases are caused by mutation in genes required for the
synthesis of type I collagen.
 Hereditary Spherocytosis
• It is caused by a mutation in the ankyrin-1 gene.
• Red blood cells become spherical, are fragile, and burst easily.
32
11.4 Beyond Mendelian
Inheritance
• Some traits are controlled by multiple alleles (multiple
allelic traits).
• The gene exists in several allelic forms, but each
individual only has two alleles.
• ABO blood types
 The alleles:
• IA = A antigen on red blood cells, anti-B antibody in plasma
• IB = B antigen on red blood cells, anti-A antibody in plasma
• i = Neither A nor B antigens on red blood cells, both anti-A and antiB antibodies in plasma
• The ABO blood type is also an example of codominance.
 More than one allele is fully expressed.
 Both IA and IB are expressed in the presence of the other.
33
ABO Blood Type
Phenotype
A
B
AB
O
Genotype
IAIA, IAi
B
B
B
I I ,I i
IAIB
ii
34
Figure 14.11
(a) The three alleles for the ABO blood groups and their
carbohydrates
IA
Allele
Carbohydrate
IB
i
none
B
A
(b) Blood group genotypes and phenotypes
Genotype
IAIA or IAi
IBIB or IBi
IAIB
ii
A
B
AB
O
Red blood cell
appearance
Phenotype
(blood group)
Beyond Mendelian
Inheritance
• Incomplete Dominance
 Heterozygote has a phenotype intermediate between
that of either homozygote.
• Homozygous red has red phenotype.
• Homozygous white has white phenotype.
• Heterozygote has pink (intermediate) phenotype.
 Phenotype reveals genotype without a testcross.
36
Incomplete Dominance
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R1R2
R1R2
eggs
R1
R2
sperm
R1
R1R1
R1R2
R2
R1R2
Offspring
R2R2
Key
1 R1R1
2 R1R2
1 R2R2
red
pink
white
37
Beyond Mendelian Inheritance
• Human examples of incomplete dominance:
 Familial Hypercholesterolemia (FH)
• Homozygotes for the mutant allele develop fatty
deposits in the skin and tendons and may have
heart attacks during childhood.
• Heterozygotes may suffer heart attacks during early
adulthood.
• Homozygotes for the normal allele do not have the
disorder.
38
Beyond Mendelian Inheritance
• Human examples of incomplete dominance:
 Incomplete penetrance
• The dominant allele may not always lead to the
dominant phenotype in a heterozygote.
• Many dominant alleles exhibit varying degrees of
penetrance.
• Example: polydactyly
– There are extra digits on hands, feet, or both.
– Not all individuals who inherit the dominant polydactyly
allele will exhibit the trait.
39
Beyond Mendelian Inheritance
• Pleiotropy occurs when a single mutant
gene affects two or more distinct and
seemingly unrelated traits.
• Marfan syndrome has been linked to a
mutated gene FBN1 on chromosome 15
which codes for the fibrillin protein.
• Marfan syndrome is pleiotropic and results
in the following phenotypes:
 Disproportionately long arms, legs, hands,
and feet
 A weakened aorta
 Poor eyesight
40
Marfan Syndrome
41
Beyond Mendelian
Inheritance
• Polygenic Inheritance:
 Occurs when a trait is governed by two or more sets
of alleles.
 Each dominant allele has a quantitative effect on the
phenotype.
 These effects are additive.
 It results in continuous variation of phenotypes within
a population.
 The traits may also be affected by the environment.
 Examples
• Human skin color
• Height
• Eye color
42
Polygenic Inheritance
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
P generation
F1 generation
F2 generation
Proportion of Population
20
—
64
15
—
64
6
—
64
1
—
64
43
Genotype Examples
Beyond Mendelian
Inheritance
• X-Linked Inheritance
 In mammals
• The X and Y chromosomes determine
gender.
• Females are XX.
• Males are XY.
44
Extending the Range of
Mendelian Genetics
• X-Linked Inheritance
 The term X-linked is used for genes that have
nothing to do with gender.
• X-linked genes are carried on the X chromosome.
• The Y chromosome does not carry these genes.
• It was discovered in the early 1900s by a group at
Columbia University, headed by Thomas Hunt
Morgan.
– Performed experiments with fruit flies
» They can be easily and inexpensively raised in
simple laboratory glassware.
» Fruit flies have the same sex chromosome pattern as
humans.
» Morgan’s experiments with X-linked genes apply
directly to humans.
45
46
X-Linked Inheritance
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
P generation
XrY
Xr
P gametes
XRXR
XR
Y
F1 generation
XRY
XRXr
eggs
F1 gametes
XR
Xr
F2 generation
sperm
XR
XRXR
XRXr
XRY
XrY
Y
Offspring
Allele Key
R
X = red eyes
Xr = white eyes
Phenotypic Ratio
females:
all red-eyed
males: 1
red-eyed
white-eyed
1
47
X-Linked Inheritance
Beyond Mendelian
Inheritance
•
Several X-linked recessive disorders occur in humans:
 Color blindness
• The allele for the blue-sensitive protein is autosomal.
• The alleles for the red- and green-sensitive pigments are on the X chromosome.
 Menkes syndrome
• It is caused by a defective allele on the X chromosome.
• It disrupts movement of the metal copper in and out of cells.
• Phenotypes include kinky hair, poor muscle tone, seizures, and low body temperature.
 Muscular dystrophy
• Causes wasting away of the muscle
• It is caused by the absence of the muscle protein dystrophin.
 Adrenoleukodystrophy
• It is an X-linked recessive disorder.
• It is a failure of a carrier protein to move either an enzyme or very long chain fatty acid
into peroxisomes.
 Hemophilia
• It is an absence or minimal presence of clotting factor VIII or clotting factor IX.
• An affected person’s blood either does not clot or clots very slowly.
49
Hemophilia and the Royal
Families of Europe
•
Hemophilia is called the bleeder’s disease because the affected person’s
blood either doesn’t clot correctly or doesn’t clot at all.
•
People with hemophilia bleed internally and externally after injury.
•
Blood transfusions or clotting factor injections help with the disorder.
•
The pedigree shows why hemophilia is referred to as “the royal disease.”
 Queen Victoria was the first of the royals to carry the gene.
 Eventually it was spread throughout the royal families of Europe through
arranged marriages between the English, Spanish, Prussian, and Russian royal
families.
50
51
X-Linked Recessive Pedigree
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
XbY
XBXB
XBY
XBXb
daughter
grandfather
XBY
XbXb
XbY
XBY
XBXB
XBXb
XbY
grandson
XBXB
XBXb
XbXb
XbY
XbY
Key
= Unaffected female
= Carrier female
= Color-blind female
= Unaffected male
= Color-blind male
X-Linked Recessive
Disorders
• More males than females are affected.
• An affected son can have parents who have the
normal phenotype.
• For a female to have the characteristic, her father must
also have it. Her mother must have it or be a carrier.
• The characteristic often skips a generation from the
grandfather to the grandson.
• If a woman has the characteristic, all of her sons will
have it.
52
Epistasis
 In epistasis, a gene at one locus alters the phenotypic
expression of a gene at a second locus
 For example, in Labrador retrievers and many other mammals,
coat color depends on two genes
 One gene determines the pigment color (with alleles B for
black and b for brown)
 The other gene (with alleles C for color and c for no color)
determines whether the pigment will be deposited in the hair
© 2011 Pearson Education, Inc.
Figure 14.12
BbEe
Eggs
1/
4 BE
1/
4 bE
1/
4 Be
1/
4
be
Sperm
1/ BE
4
1/
BbEe
4 bE
1/
4 Be
1/
4 be
BBEE
BbEE
BBEe
BbEe
BbEE
bbEE
BbEe
bbEe
BBEe
BbEe
BBee
Bbee
BbEe
bbEe
Bbee
bbee
9
: 3
: 4
Linked Genes
Mapping the Distance Between Genes Using
Recombination Data: Scientific Inquiry
• Alfred Sturtevant, one of Morgan’s students,
constructed a genetic map, an ordered list of
the genetic loci along a particular chromosome
• Sturtevant predicted that the farther apart two
genes are, the higher the probability that a
crossover will occur between them and
therefore the higher the recombination
frequency
© 2011 Pearson Education, Inc.
• A linkage map is a genetic map of a
chromosome based on recombination
frequencies
• Distances between genes can be expressed
as map units; one map unit represents a 1%
recombination frequency
• Map units indicate relative distance and order,
not precise locations of genes
© 2011 Pearson Education, Inc.
Figure 15.11
RESULTS
Recombination
frequencies
9%
Chromosome
9.5%
17%
b
cn
vg
• Sturtevant used recombination frequencies to
make linkage maps of fruit fly genes
• Using methods like chromosomal banding,
geneticists can develop cytogenetic maps of
chromosomes
• Cytogenetic maps indicate the positions of
genes with respect to chromosomal features
© 2011 Pearson Education, Inc.
Figure 15.12
Short
aristae
0
Mutant phenotypes
Black Cinnabar
Vestigial Brown
body eyes
wings
eyes
48.5 57.5
67.0
Long aristaeGray Red Normal
(appendagesbody eyes wings
on head) Wild-type phenotypes
104.5
Red
eyes
X Inactivation in Female Mammals
• In mammalian females, one of the two X
chromosomes in each cell is randomly
inactivated during embryonic development
• The inactive X condenses into a Barr body
• If a female is heterozygous for a particular gene
located on the X chromosome, she will be a
mosaic for that character
© 2011 Pearson Education, Inc.
Figure 15.8
Early embryo:
Two cell
populations
in adult cat:
Active X
X chromosomes
Allele for
orange fur
Allele for
black fur
Cell division and
X chromosome
inactivation
Inactive X
Black fur
Active X
Orange fur