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Chapter 4.
Modification of Mendelian
Ratios
Inheritance Patterns are Often More
Complex than Predicted by Simple
Mendelian Genetics
• The relationship between genotype and phenotype is
rarely as simple as in the pea plant characters Mendel
studied.
• Many heritable characters are not determined by only
one gene with two alleles.
• However, the basic principles of segregation and
independent assortment apply even to more complex
patterns of inheritance.
Outline of Extensions to
Mendel’s Analysis
• Single-gene inheritance
– In which pairs of alleles show deviations from
complete dominance and recessiveness
– In which different forms of the gene are not limited
to two alleles
– Where one gene may determine more than one
trait
• Multifactorial inheritance in which the phenotype
arises from the interaction of one or more genes with
the environment, chance, and each other
Extending Mendelian Genetics for a Single
Gene
• Inheritance of characters by a single gene may deviate
from simple Mendelian patterns in the following
situations:
– When alleles are not completely dominant or
recessive.
– When a gene has more than two alleles.
– When a gene produces multiple phenotypes.
The Relation Between Dominance and
Phenotype
• A dominant allele does not subdue a recessive allele; alleles
don’t interact.
• Alleles are simply variations in a gene’s nucleotide
sequence.
• For any character, dominance/recessiveness relationships of
alleles depend on the level at which we examine the
phenotype.
Degrees of Dominance
• Complete dominance occurs when phenotypes of the
heterozygote and dominant homozygote are identical.
• In incomplete dominance, the phenotype of F1 hybrids
is somewhere between the phenotypes of the two
parental varieties.
• In codominance, two dominant alleles affect the
phenotype in separate, distinguishable ways.
Dominance is Not Always Complete
• Crosses between true-breeding strains can produce hybrids
with phenotypes different from both parents.
– Incomplete dominance
• F1 hybrids that differ from both parents express an
intermediate phenotype.
• Neither allele is dominant or recessive to the other.
• Phenotypic ratios are same as genotypic ratios.
– Codominance
• F1 hybrids express phenotype of both parents
equally.
• Phenotypic ratios are same as genotypic ratios.
Incomplete Dominance in Snapdragons
Copyright © 2010 Pearson Education, Inc.
P generation
Red
White
RR
rr
r
R
Gametes
F1 generation
Pink
Rr
Gametes
1
–
2
R
1
–
2
r
Sperm
1
–
2
F2 generation
R
1
–
2
r
1
–
2
R
RR
rR
1
–
2
r
Rr
rr
Eggs
Codominant Blood Group Alleles
The MN Blood Type
Genotype
Phenotype
LMLM
M
LMLN
MN
LNLN
N
Summary of Dominance Relationships
A Gene Can Have More Than Two Alleles
• Genes may have multiple alleles that segregate in
populations.
• Alleles may be unique to every pair of alleles in an
individual.
Multiple Alleles
• Most genes exist in populations in more than two allelic
forms.
• For example, the four phenotypes of the ABO blood
group in humans are determined by three alleles for the
enzyme (I) that attaches A or B carbohydrates to red
blood cells: IA, IB, and i.
• The enzyme encoded by the IA allele adds the A
carbohydrate, whereas the enzyme encoded by the IB
allele adds the B carbohydrate; the enzyme encoded by
the i allele adds neither.
ABO Types are Determined by Three
Alleles
Allele
IA
Carbohydrate
A
IB
B
i
none
(a) The three alleles for the ABO blood groups
and their associated carbohydrates
Genotype
Red blood cell
appearance
Phenotype
(blood group)
IAIA or IA i
A
IBIB or IB i
B
IAIB
AB
ii
O
(b) Blood group genotypes and phenotypes
Multiple Alleles for the ABO Blood Groups
Bombay Phenotype
• Child from both O type parents can have A or B type.
• Bombay phenotype actually arises from homozygosity for
a mutant recessive allele (hh) of a second gene that
masks the effects of any ABO alleles that might be
present.
Frequency of Dominant Alleles
• Dominant alleles are not necessarily more common in
populations than recessive alleles.
• For example, one baby out of 400 in the United States is
born with extra fingers or toes.
• The allele for this unusual trait is dominant to the allele
for the more common trait of five digits per appendage.
• In this example, the recessive allele is far more prevalent
than the population’s dominant allele.
Dual Role of Allele
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Genes and Traits
Pleiotropy
• The phenomenon of a single gene determining a
number of distinct and seemingly unrelated
characteristics
• Most genes have multiple phenotypic effects, a
property called pleiotropy: one gene influencing many
characteristics.
• If proteins encoded by important genes play pivotal
roles in diverse biological processes, mutations in
those genes may lead to pleiotropic effects.
• For example, pleiotropic alleles are responsible for the
multiple symptoms of certain hereditary diseases, such
as cystic fibrosis and sickle-cell disease.
• The gene
–
–
–
–
–
for sickle cell disease
Affects the type of hemoglobin produced
Affects the shape of red blood cells
Causes anemia
Causes organ damage
Is related to susceptibility to malaria
• This sickling creates a cascade of symptoms,
demonstrating the pleiotropic effects of this allele.
• Doctors can use
regular blood
transfusions to
prevent brain
damage and new
drugs to prevent
or treat other
problems.
Degree of dominance
Example
Description
Complete dominance
of one allele
Heterozygous phenotype
same as that of homozygous dominant
Incomplete dominance
of either allele
Heterozygous phenotype
intermediate between
the two homozygous
phenotypes
PP
Pp
C RC R
Codominance
Multiple alleles
Pleiotropy
Heterozygotes: Both
phenotypes expressed
In the whole population,
some genes have more
than two alleles
One gene is able to
affect multiple
phenotypic characters
C RC W C W C W
IAIB
ABO blood group alleles
IA , IB , i
Sickle-cell disease
Different Dominance Relations
Do Variations on Dominance Relations
Negate Mendel’s Law of Segregation?
• Dominance relations affect phenotype and have no
bearing on the segregation of alleles.
• Alleles still segregate randomly.
• Gene products control expression of phenotypes
differently.
• Mendel’s law of segregation still applies.
• Interpretation of phenotype/genotype relation is more
complex.
Modified Ratio of the Dihybrid Inheritance
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Two Genes can Interact to Determine
One Trait
• A gene interaction in which the effects of an alleles at
another gene is known as epistasis.
• In epistasis, a gene at one locus alters the phenotypic
expression of a gene at a second locus.
• The allele that is doing the masking is epistatic to the
gene that is being masked.
• Recessive vs. Dominant epistasis
Recessive Epistasis
• For example, in mice 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.
BbCc
´
BbCc
Sperm
1/
4 BC
1/
4 bC
1/
4 Bc
1/
4 bc
Eggs
1/
1/
1/
1/
4 BC
BBCC
BbCC
BBCc
BbCc
BbCC
bbCC
BbCc
bbCc
BBCc
BbCc
BBcc
Bbcc
BbCc
bbCc
Bbcc
bbcc
4 bC
4 Bc
4 bc
9
: 3
: 4
Copyright © 2010 Pearson Education, Inc.
Dominant Epistasis
Summer squash exhibiting the fruit-shape phenotypes disc
(white), long (orange gooseneck), and sphere (bottom left).
An Example: Fruit Color in Summer Squash
P:
F1:
F2:
AABB (white)
X aabb (green)
AaBb (white) X AaBb (white)
9/16
3/16
3/16
1/16
A-B- : white
A-bb : white
aaB- : yellow
aabb : green
Finally, the phenotypic ratio is 12:3:1.
• Epistasis in which the dominant allele of one gene hides
the effects of another gene.
• When two white F1 dihybrids (AaBb) are crossed the F2
phenotypic ratio is 12 white: 3 yellow: 1 green.
•
12 white includes two genotypic classes (9 A-B- and 3
aaB-).
• The dominant allele A results in white fruit color
regardless of the genotype at a second locus B.
Complementary Gene Action
• 9:7 ratio of purple to white F2 plants indicates that at
least one dominant allele for each gene is necessary for
the development of purple color.
• Enzymes specified by the dominant alleles of the two
genes may both be necessary for completion of a
biochemical pathway for pigment production.
• Recessive alleles of both genes specify inactive enzymes.
The basis of modified dihybrid F2 phenotypic ratios,
resulting from crosses between doubly heterozygous F1
individuals.
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Do Variations on Allelic Interation Negate
Mendel’s Law of Independent Assortment?
• The added complexity of inheritance does not detract
from the validity of Mendel’s conclusions.
• The F2 phenotypic ratio in each example has been
expressed in sixteenth.
Question
• p85: Insights and Solutions
Copyright © 2010 Pearson Education, Inc.
• Consider the problem of comb-shape inheritance in
chickens, where walnut, pea, rose, and single are the
observed distinct phenotypes. How is comb shape
inherited, what are the genotypes of the P1 generation
of each cross? Use the following data:
Cross
Cross
Cross
Cross
1
2
3
4
:
:
:
:
single X single à all single
walnut X walnut à all walnut
rose X pea à all walnut
F1 X F1 of cross 3
walnut X walnut à 93 walnut
28 rose
32 pea
10 single
Question
• p87: Problem #7
• In some plants, a red pigment, cyanidin, is synthesized from a
colorless precursor. The addition of a hydroxyl group (-OH) to the
cyanidin molecule causes it to become purple. In a cross between
two randomly selected purple plants, the following results are
obtained:
94 purple: 31 red: 43 colorless
1) How many genes are involved in determining these flower colors?
2) Which genotypic combinations produce which phenotypes?
Question
• p86: Insights and Solutions
• In radishes, flower color may be red, purple, or white.
The edible portion of the radish may be long or oval.
When only flower color is studied, no dominance is
evident, and red X white crosses yield all purple. If these
F1 purples are interbred, the F2 generation consists of ¼
red: ½ purple: ¼ white. Regarding radish shape, long is
dominant to oval in a normal Mendelian fashion.
1) Determine the F1 and F2 phenotypes from a cross
between a true-breeding red, long radish and one that
is white and oval. Be sure to define all gene symbols
initially.
2) A red oval plant was crossed with a plant of unknown
genotype and phenotype, yielding the following
offspring: Determine the genotype and phenotype of
the unknown plant.
103 red long: 101 red oval: 98 purple long: 100 purple oval
Continuous Traits
Polygenic Inheritance
• Quantitative characters are those that vary in the
population along a continuum.
• Quantitative variation usually indicates polygenic
inheritance, an additive effect of two or more genes on
a single phenotype (many genes influence one trait).
• Skin color in humans is an example of polygenic
inheritance.
´
AaBbCc
Sperm
• A cross between two
AaBbCc individuals
(intermediate skin
shade) would produce
offspring covering a
wide range of shades.
1/
1/
8
1/
8
1/
8
1/
8
1/
1/
8
1/
1/
8
8
1/
8
1/
64
15/
8
1/
1/
8
8
8
1/
8
1/
8
1/
8
AaBbCc
8
Phenotypes:
Number of
dark-skin alleles:
1/
64
0
6/
64
1
15/
64
2
20/
3
64
4
6/
64
5
1/
64
6
• Individuals with
intermediate skin shades
would be the most likely
offspring, but very light
and very dark individuals
are possible as well.
• The range of phenotypes
forms a normal
distribution.
Mendelian Explanation
Relationship among
genes
Epistasis
Example
Description
One gene affects
the expression of
another
BbCc
BbCc
BC bC Bc bc
BC
bC
Bc
bc
9
Polygenic
inheritance
A single phenotypic
character is
affected by
two or more genes
AaBbCc
:3
:4
AaBbCc
Complementation Test
• To discover whether a particular phenotype arises
from mutations in the same or separate genes
• The occurrence of complementation reveals genetic
heterogeneity.
• Complementation test cannot be used if either of the
mutations is dominant to the wildtype.
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Examples
Some Genes on the Same Chromosome
Assort Together More Often Than Not
• In dihybrid crosses, departures from a 1:1:1:1 ratio
of F1 gametes indicate that the two genes are on
the same chromosome.
– In a sex linked cross
Inheritance of Sex-Linked Genes
• The sex chromosomes have genes for many characters
unrelated to sex.
• A gene located on either sex chromosome is called a
sex-linked gene.
• In humans, sex-linked usually refers to a gene on the
larger X chromosome.
Linkage at a Sex-Linked Gene
- The F1 and F2 results of
T. H. Morgan's reciprocal
crosses involving the Xlinked white mutation in
Drosophila melanogaster.
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EXPERIMENT
P
Generation
F1
Generation
RESULTS
F2
Generation
´
All offspring
had red eyes
CONCLUSION
w+
P
X
Generation X
´
w+
X
Y
w
Eggs
F1
Generation
Sperm
w+
w+
w+
w
w+
Eggs
F2
Generation
w
w+
Sperm
w+
w+
w
w
w
w+
Copyright © 2010 Pearson Education, Inc.
Inheritance of Sex-Linked Genes
XNXN ´
Sperm Xn
X nY
(a)
Sperm XN
Y
Eggs XN XNXn XNY
XN
XNXn
´
XNY
Xn
(b)
Sperm Xn
Y
Eggs XN XNXN XNY
XNXn XNY
XNXn
´
X nY
Y
Eggs XN XNXn XNY
X nX N X nY
Xn
(c)
X nX n X nY
• Sex-linked genes follow specific patterns of inheritance.
• For a recessive sex-linked trait to be expressed.
– A female needs two copies of the allele.
– A male needs only one copy of the allele.
• Sex-linked recessive disorders are much more common
in males than in females.
• Some disorders caused by recessive alleles on the X
chromosome in humans:
– Color blindness
– Duchenne muscular dystrophy
– Hemophilia
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Question
• p86: Insights and Solutions
• Consider the two very limited unrelated pedigrees shown here. Of
the four combinations of X-linked recessive, X-linked dominant,
autosomal recessive, and autosomal dominant, which modes of
inheritance can be absolutely ruled out in each case?
Copyright © 2010 Pearson Education, Inc.
Question
• p86: Insights and Solutions
• In humans, red-green color blindness is inherited as an
X-linked recessive trait. A woman with normal vision
whose father is color blind marries a male who has
normal vision. Predict the color vision of their male and
female offspring.
Copyright © 2010 Pearson Education, Inc.
Question
• p88: Problem #12
• In goats, development of the beard is due to a recessive gene. The
following cross involving true-breeding goats was made and carried
to the F2 generation:
P: beard female x beardless male
F1: all bearded males and beardless females
F1 x F1:
1/8 beardless males
3/8 bearded males
3/8 beardless females
1/8 bearded females
1) Offer an explanation for the inheritance and expression of this
traits.
2) Propose one or more crosses to test your hypothesis.
Sex-Limited vs. Sex-Influenced Inheritance
Only in male with the hh
genotype results in cock
feathering.
When females inherit
the BB genotype, the
phenotype is less
pronounced.
Penetrance and Expressivity
• Sometimes, a genotype is not expressed at all.
• The trait caused by a genotype is expressed to varying
degrees.
• Penetrance: how mant members of a population with a
particular genotype show the expected phenotype
(complete vs. incomplete)
• Expressivity: the degree or intensity with which a
particular genotype is expressed in a phenotype
Variable Expressivity in eyeless Mutation
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Environmental Factors in Phenotypes
§ Phenotypic variations are influenced by the
environment.
• Skin color is affected by exposure to sunlight.
• Susceptibility to diseases, such as cancer, has
hereditary and environmental components.
Environmental Effects
Permissive vs. Restrictive
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.
X chromosomes
Early embryo:
Two cell
populations
in adult cat:
Active X
Allele for
orange fur
Allele for
black fur
Cell division and
X chromosome
inactivation
Inactive X
Black fur
Orange fur
Active X
Genomic Imprinting
• For a few mammalian traits, the phenotype depends on
which parent passed along the alleles for those traits.
• Such variation in phenotype is called genomic
imprinting.
• Genomic imprinting involves the silencing of certain
genes that are “stamped” with an imprint during gamete
production.
Normal Igf2 allele
is expressed
Paternal
chromosome
Maternal
chromosome
Normal Igf2 allele
is not expressed
(a) Homozygote
Wild-type mouse
(normal size)
Mutant Igf2 allele
inherited from mother
Mutant Igf2 allele
inherited from father
Normal size mouse
(wild type)
Dwarf mouse
(mutant)
Normal Igf2 allele
is expressed
Mutant Igf2 allele
is expressed
Mutant Igf2 allele
is not expressed
Normal Igf2 allele
is not expressed
(b) Heterozygotes
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• It appears that imprinting is the result of the methylation
(addition of –CH3) of DNA.
• Genomic imprinting is thought to affect only a small
fraction of mammalian genes.
• Most imprinted genes are critical for embryonic
development.
Phenocopy
• A change in phenotype arising from environmental
factors that mimic the effects of a mutation in a gene
• Phenocopies are not heritable because they do not
arise from a change in a gene.
Extracellular Inheritance
• Organelle heredity: the phenotype of an individual
organism is affected by the expression of genes
contained in the DNA of mitochondria or chloroplast.
• Maternal effect: the phenotype of an individual
organism is determined by genetic information
expressed in the gamete of the mother.
Copyright © 2010 Pearson Education, Inc.
Copyright © 2010 Pearson Education, Inc.
Copyright © 2010 Pearson Education, Inc.