Classical Genetics
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Mendelian inheritance describes
inheritance patterns that obey two laws
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Law of segregation
Law of independent assortment
Simple Mendelian inheritance involves
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A single gene with two different alleles
Alleles display a simple dominant/recessive
relationship
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Prevalent alleles in a population are termed wild-type alleles
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These typically encode proteins that
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Alleles that have been altered by mutation are termed
mutant alleles
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Function normally
Are made in the right amounts
These tend to be less common in natural populations
They are likely to cause a reduction in the amount or function of the
encoded protein
Such mutant alleles are often inherited in a recessive fashion
A particular gene variant is not usually considered an allele
of a given gene unless it is present in at least 1% of the
population.
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Rare gene variants (<1%) are termed polymorphisms rather than
allelic variants
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Consider, for example, the traits that Mendel studied
Wild-type (dominant) allele Mutant (recessive) allele
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Purple flowers
White flowers
Axial flowers
Terminal flowers
Yellow seeds
Green seeds
Round seeds
Wrinkled seeds
Smooth pods
Constricted pods
Green pods
Yellow pods
Tall plants
plants
Another example is from Drosophila
Wild-type (dominant) allele Mutant (recessive) allele
Red eyes
White eyes
Normal wings
Miniature wings
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4-7
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Human genetic diseases caused by recessive
mutant alleles
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The mutant alleles do not produce fully functional
proteins
Extended Mendelian Inheritance Patterns
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Incomplete dominance
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Co-dominance
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Heterozygosity at a locus creates a phenotype that is more
beneficial or more deterimental than homozygosity of either locus
with any allele
Lethality
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Heterozygosity at a locus produces a single unique phenotype
different from either homozygous condition
Overdominance
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Heterozygosity at a locus produces a third 3 phenotype intermediate
to the two homozygous phenotypes
Homozygosity of an allele kills the cell or organism
Penetrance
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A measure of how variation in expression of a given allele occurs
incomplete penetrance describes the lack of effect a deleterious
allele might have in an individual carrying it
Extended Mendelian Inheritance Patterns
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Sex-linked
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Sex-influenced
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inheritance of genes on that are unique to a sex chromosomes
pseudoautosomal genes – genes on both sex chromosomes appear
to be on autosomes
An allele is expressed differently in each sex. Behaving dominantly in
one sex and recessively in the other
Sex-limited
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An allele is only expressed in one or the other sex
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4-5
Complete Dominance/Recessiveness
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recessive allele does not affect the phenotype
of the heterozygote
two possible explanations
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50% of the normal protein is enough to
accomplish the protein’s cellular function
The normal gene is “up-regulated” to compensate
for the lack of function of the defective allele
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The heterozygote may actually produce more than 50%
of the functional protein
Simple Mendelian Inheritance
Figure 4.1
Lethal Alleles
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Essential genes are those that are absolutely
required for survival
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The absence of their protein product leads to a lethal
phenotype
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It is estimated that about 1/3 of all genes are essential for
survival
Nonessential genes are those not absolutely
required for survival
A lethal allele is one that has the potential to
cause the death of an organism
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These alleles are typically the result of mutations in
essential genes
usually recessive, but can be dominant
Lethal Alleles
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Many lethal alleles prevent cell division
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Some lethal allele exert their effect later in life
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Huntington disease
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Characterized by progressive degeneration of the nervous
system, dementia and early death
The age of onset of the disease is usually between 30 to 50
Conditional lethal alleles may kill an organism only
when certain environmental conditions prevail
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Temperature-sensitive (ts) lethals
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A developing Drosophila larva may be killed at 30 C
But it will survive if grown at 22 C
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Semilethal alleles
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Kill some individuals in a population, not all of them
Environmental factors and other genes may help
prevent the detrimental effects of semilethal genes
A lethal allele may produce ratios that seemingly
deviate from Mendelian ratios
An example is the “creeper” allele in chicken
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Creepers have shortened legs and must creep along
Such birds also have shortened wings
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Creeper chicken are heterozygous
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4-13
Phenotypic Ratios Associated with Lethal Alleles
Creeper X Normal
Creeper X Creeper
1 creeper : 1 normal
1 normal : 2 creeper
Creeper is a dominant allele
Creeper is lethal in the
homozygous state
Incomplete Dominance
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heterozygote exhibits a phenotype
intermediate to the homozygotes
Also called intermediate dominance or
dosage effect
Example:
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Flower color in the four o’clock plant governed
by 2 alleles
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CR = wild-type allele for red flower color
CW = allele for white flower color
Incomplete Dominance
1:2:1 phenotypic
ratio NOT the 3:1
ratio observed in
simple Mendelian
inheritance
In this case, 50% of
the CR protein is not
sufficient to produce
the red phenotype
Figure 4.2
Incomplete Dominance
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complete or incomplete dominance can
depend on level of examination
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Gene Dosage – A form of intermediate
dominance
Alleles of white –
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X-linked eye color gene in Drosophila
W – red (wildtype gene)
w - white
we - eosin
we allele was expressed with different
intensity in the two sexes
 Homozygous females  eosin
 Males  light-eosin
eosin ♀ and eosin ♂ phenotypes
Gene Dosage
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Morgan & Bridges hypothesized that
difference in intensity was due to the
difference in number of X chromosomes
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Female has two copies of the “eosin color
producer” allele
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Males have only one copy of the allele
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Eyes will contain more color
Eyes will be paler
This is an example of gene dosage effect
Multiple Alleles
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The term multiple alleles is used to describe
situations when three or more different alleles
of a gene exist
Examples:
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ABO blood
Coat color in many species
Eye color in Drosophila
Multiple Alleles
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ABO blood phenotype is determined by multiple
alleles
ABO type result of antigen on surface of RBCs
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Antigen A, which is controlled by allele IA
Antigen B, which is controlled by allele IB
Antigen O, which is controlled by allele i
N-acetylgalactosamine
Co-dominance
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Alleles IA and IB are codominant
They both encode functional enzymes and
are simultaneously expressed in a
heterozygous individual
Allele i is recessive to both IA and IB
Multiple Alleles
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coat color in rabbits
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C (full coat color)
cch (chinchilla pattern of coat color)
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ch (himalayan pattern of coat color)
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Pigmentation in only certain parts of the body
c (albino)
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Partial defect in pigmentation
Lack of pigmentation
INSERT Figure 4.4
Multiple Alleles
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Dominance hierarchy will exist for multiple
alleles called an allelic series
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allelic series for ABO type
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allelic series for rabbit coat color alleles :
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I A = IB > i
C > cch > ch > c
allelic series for alleles of white gene
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W+/_ > we/we > we/w > w/w = w/Y
Conditional Mutations
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The ch allele is a temperature-sensitive
conditional mutant
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The enzyme is only functional at low
temperatures
Therefore, dark fur will only occur in cooler areas
of the body
Overdominance
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Overdominance is the phenomenon in which a
heterozygote is more vigorous than both of the
corresponding homozygotes
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Example:
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Sickle-cell heterozygotes are resistant to malaria
increased disease resistance in plant hybrids
Incomplete Penetrance
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In some instances, a dominant allele is not
expressed in a heterozygote individual
Example = Polydactyly
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Autosomal dominant trait
Affected individuals have additional fingers
and/or toes
A single copy of the polydactyly allele is usually
sufficient to cause this condition
In some cases, however, individuals carry the
dominant allele but do not exhibit the trait
Figure 4.11
Inherited the polydactyly allele from
his mother and passed it on to a
daughter and son
Does not exhibit the trait himself
even though he is a heterozygote
Incomplete Penetrance
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The term indicates that a dominant allele does not
always “penetrate” into the phenotype of the
individual
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The measure of penetrance is described at the
population level
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If 60% of heterozygotes carrying a dominant allele
exhibit the trait allele, the trait is 60% penetrant
Note:
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In any particular individual, the trait is either penetrant or
not
Expressivity
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Expressivity is the degree to which a trait is
expressed
In the case of polydactyly, the number of extra
digits can vary
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A person with several extra digits has high expressivity
of this trait
A person with a single extra digit has low expressivity
Penetrance & Expressivity
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The molecular explanation of expressivity and
incomplete penetrance may not always be
understood
In most cases, the range of phenotypes is thought
to be due to influences of the
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Environment
and/or
Other genes (genetic background)