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Powerpoint Lecture Outline
Human Genetics
Concepts and Applications
Eighth Edition
Ricki Lewis
Prepared by
Dubear Kroening
University of
Wisconsin-Fox Valley
5-1
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Chapter 5
Extensions and Exceptions to
Mendel’s Laws
5-2
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Exceptions to Mendel’s Law
• Mendel’s traits showed two distinct forms
• Most genes do not exhibit simple inheritance
• Genotypic ratios persist but phenotypic ratios
may vary because of interactions between
–
–
–
–
–
Alleles
Other genes
Non-nuclear genes
Segregation of genes on same chromosome
Environment
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Lethal Alleles
Some allele combinations are lethal
Figure 5.1b
5-4
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Multiple Alleles
• An individual carries two alleles for each gene
• A population can have many alleles among the
individual members
• Examples
– PKU gene has over 300 alleles resulting in four basic
phenotypes
– CF gene has over 1000 alleles
• Genes can mutate in many ways in their DNA
sequence
5-5
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Incomplete Dominance
• The heterozygous phenotype is distinct from either
homozygous phenotype
• It may be an intermediate phenotype
Figure 5.2
5-6
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Codominant Alleles
Both alleles are expressed in the heterozygotes
Example:
The ABO gene encodes a cell surface protein
• A allele produces A antigen
• B alleles produce B antigen
• O allele does not produce antigens
• A and B antigens may be present on the same cell
• Alleles A and B are codominant
5-7
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Table 5.1
5-8
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Codominant
Alleles
Figure 5.3
5-9
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Offspring from Parents
with Blood Type A and Blood Type B
Figure 5.4
5-10
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Epistasis
One gene affects the expression of a second gene
Example: H gene is epistatic to the ABO gene.
• H protein attaches a molecule to the cell surface
to which the A or B antigens are attached
• hh genotype = no H protein
• Without H protein the A or B antigens can not be
attached to the cell
• All hh genotypes have the phenotype of type O,
although the ABO blood group can be
anything (A, B, AB, or O)
5-11
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Incomplete Penetrance
• The phenotype is not always observed among
individuals carrying the genotype – express or
not
– DD or Dd - only 80% show polydactyly
Variable Expressivity
• A phenotype that varies in intensity
 Polydactyly two extra digits on each hand and foot
vs. one extra digit on one foot
 Individuals with the same genotype for familial
hypercholesterolemia have varying levels of
symptoms
5-12
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5-13
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Pleiotropy
One gene has many symptoms
or controls several functions
Example: porphyria variegata
Figure 5.5a
Figure 5.5b
Photo © North Wind Picture Archives
5-14
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Genetic Heterogeneity
• Different genes can produce identical phenotypes
 Hearing loss
 Osteogenesis imperfecta
• Genes may encode for different enzymes in a
biochemical pathway
 Clotting disorders
5-15
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Phenocopy
• Appears inherited but is caused by the environment
• May have symptoms that resemble an inherited trait
or occur within families
Examples:
• Exposure to teratogens
– Thalidomide causes limb defects similar to
inherited phocomelia
– Hydroquinone exposure looks like alkaptonuria
• Infection
– AIDS virus can be passed from mother to child,
looking like it is inherited
5-16
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Importance of Human Genome
Sequence
• Complications to Mendelian inheritance
more common than originally thought
• Overlapping of definitions – Marfan
syndrome has both epistasis and
genetic heterogeneity
5-17
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Table 5.3
5-18
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Mitochondrion
•
•
•
•
•
•
•
Organelle providing cellular energy
Contains small circular DNA
No crossing over or DNA repair
High exposure to free radicals
Mutation rate is greater than nuclear DNA
37 genes without noncoding sequences
Mitochondrial genes are transmitted from mother
to all of her offspring
5-19
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Mitochondrial
Inheritance
Figure 5.8
Figure 5.7
5-20
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Table 5.4
5-21
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Mitochondrial Disorders
• Mitochondrial myopathies – weak
muscles
• Leber optic atrophy – impairs vision
• Ooplasmic transfer technique can
enable woman to avoid transmitting a
mitochondrial disorder
5-22
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Heteroplasmy
• Many copies of the mitochondrial genome
per cell
• May have more than one allele for the same
gene in the same cell
• Heteroplasmy is the condition where
mitochondrial DNA sequence is not the
same in all copies
5-23
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Linkage
• Linkage is the transmission of two genes
on the same chromosome
• Two genes on the same chromosome
will not assort randomly in meiosis
5-24
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Expected Results in a Dihybrid Cross
Figure 5.10
5-25
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Parents
P
p
L
l
Genotype PpLl
Genes not linked
Self-cross
P
L
p
l
Genotype PpLl
Genes linked
Self-cross
Figure 5.10
5-26
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Parents
P
p
L
l
Genotype PpLl
Genes not linked
Self-cross
P
L
p
l
Genotype PpLl
Genes linked
Self-cross
F1
5-27
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Parents
P
p
L
P
L
l
Genotype PpLl
Genes not linked
Self-cross
F1
Male
gametes
Genotype PpLl
Genes linked
Self-cross
Female gametes
PL
pl
Female gametes
PL
Pl
pL
pl
PL
Pl
p
l
Male
gametes
PL
pl
pL
pl
5-28
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Parents
P
p
L
l
Genotype PpLl
Genes not linked
Self-cross
F1
Female gametes
PL
Pl
pL
pl
PL
Pl
PPLL PPLl PpLL PpLl
PPLl PPll PpLl Ppll
Male
gametes
PpLL PpLl ppLL ppLl
pL
pl
P
L
p
l
Genotype PpLl
Genes linked
Self-cross
Female gametes
PL
pl
Male PL PPLL PpLl
gametes
pl PpLl ppll
PpLl Ppll ppLl ppll
5-29
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Parents
P
p
L
l
Genotype PpLl
Genes not linked
Self-cross
F1
Female gametes
PL
Pl
pL
pl
PL
Pl
PPLL PPLl PpLL PpLl
PPLl PPll
PpLl Ppll
Male
gametes
PpLL PpLl ppLL ppLl
pL
pl
P
L
p
l
Genotype PpLl
Genes linked
Self-cross
Female gametes
PL
pl
Male PL PPLL PpLl
gametes
pl PpLl ppll
Phenotypic ratio 3:
PpLl Ppll ppLl ppll
Phenotypic ratio 9:3
5-30
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Parents
P
p
L
l
Genotype PpLl
Genes not linked
Self-cross
PL
Pl
PPLL PPLl PpLL PpLl
PPLl PPll
PpLl Ppll
Male
gametes
PpLL PpLl ppLL ppLl
pL
pl
p
l
Genotype PpLl
Genes linked
Self-cross
Female gametes
PL
Pl
pL
pl
F1
P
L
Female gametes
PL
pl
Male PL PPLL PpLl
gametes
pl PpLl ppll
Phenotypic ratio 3:
PpLl Ppll ppLl ppll
Phenotypic ratio 9:
5-31
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Parents
P
p
L
l
Genotype PpLl
Genes not linked
Self-cross
F1
Female gametes
PL
Pl
pL
pl
PL
Pl
PPLL PPLl PpLL PpLl
PPLl PPll
PpLl Ppll
Male
gametes
PpLL PpLl ppLL ppLl
pL
pl
P
L
p
l
Genotype PpLl
Genes linked
Self-cross
Female gametes
PL
pl
Male PL PPLL PpLl
gametes
pl PpLl ppll
Phenotypic ratio 3:
PpLl Ppll ppLl ppll
Phenotypic ratio 9:3:3
5-32
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Parents
P
p
L
l
Genotype PpLl
Genes not linked
Self-cross
F1
Female gametes
PL
Pl
pL
pl
PL PPLL PPLl PpLL PpLl
Pl
PPLl PPll
PpLl Ppll
Male
gametes
pL PpLL PpLl ppLL ppLl
pl
P
L
p
l
Genotype PpLl
Genes linked
Self-cross
Female gametes
PL
pl
Male PL PPLL PpLl
gametes
pl PpLl ppll
Phenotypic ratio 3:1
PpLl Ppll ppLl ppll
Phenotypic ratio 9:3:3:1
5-33
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Recombination
• During crossing over in prophase I chromosomes
recombine
• New combinations of alleles are created
• Parental chromosomes have the original
configuration
• Recombinant chromosomes have new
combinations of alleles
Figure 5.12
5-34
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Crossing over Disrupts Linkage
Figure 5.11
5-35
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Recombination
• Frequency of recombination is based on
percentage of meiotic divisions that result in
breakage of linkage between parental alleles
• The frequency of recombination between two
genes is proportional to the distance between
the genes
Figure 5.13
5-36
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Linkage versus Non-linkage
Figure 5.14
5-37
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Linkage Map
• A linkage map is a diagram indicating the relative distance
between genes.
• 1% recombination = 1 map unit = 1 centiMorgan (cM)
• Map distances are additive
Figure 5.16
5-38
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Inheritance of Linked Genes
The genes for Rh factor (R) and anemia (E) are linked,
but some recombination occurs between the two genes
Figure 5.15
Parent 2 (mother) produces 4% recombinant gametes,
therefore the Rh factor gene and the anemia gene are
4 map units or 4 cM apart
5-39
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Linkage Disequilibrium (LD)
Is the non-random association between alleles
at two locations on a chromosome
Example:
• Two genes, A and B, exist in a population
• Genes are in equilibrium if the frequency of
chromosomes with AB=Ab=aB=ab
• The genes are in linkage disequilibrium if the
frequency of one allele of gene A is seen more
frequently with a particular allele of gene B
5-40
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LOD Score
• Is the logarithm of the odds ratio calculated by
how often genes and markers are inherited
together
• Is the likelihood that particular crossover
frequency data indicates linkage
• LOD scores of 3 or greater are considered
significant and indicate the data would be
observed by chance 1/1000 times
• Was used when disease genes were not
identified
5-41
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Haplotype
• Is the set of alleles inherited on one
chromosome
• Make it possible to track which parent
transmits which genes
5-42
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Mapping with
Haplotypes
Gene A
Gene B
Gene C
Gene D
Gene E
11
11
11
11
11
Segregation of a dominant
trait is observed in this family
(filled symbols).
22
22
22
22
22
12
12
12
12
12
33
33
33
33
33
44
44
44
44
44
34
34
34
34
34
The trait segregates with
the yellow haplotype.
14
14
14
14
14
23
23
23
23
23
14
14
14
13
13
13
13
13
13
13
14
14
14
14
14
23
23
24
24
24
23
23
23
23
23
5-43
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Mapping with
Haplotypes
Gene A
Gene B
Gene C
Gene D
Gene E
III-3 and III-6 inherit
recombinant chromosomes.
The location of the recombination
events indicate that the gene
for this trait is located
between genes B and D.
14
14
14
14
14
11
11
11
11
11
22
22
22
22
22
12
12
12
12
12
23
23
23
23
23
14
14
14
13
13
33
33
33
33
33
44
44
44
44
44
34
34
34
34
34
13
13
13
13
13
14
14
14
14
14
23
23
24
24
24
23
23
23
23
23
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Recombinant chromosomes