Classical Genetics
Mendelian inheritance describes inheritance patterns that obey two laws Law of segregation Law of independent assortment
Simple Mendelian inheritance involves A single gene with two different alleles Alleles display a simple dominant/recessive
relationship
Prevalent alleles in a population are termed wild-type alleles
These typically encode proteins that Function normally Are made in the right amounts
Alleles that have been altered by mutation are termed mutant alleles
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.
Rare gene variants (<1%) are termed polymorphisms rather than allelic variants
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Wild-type (dominant) allele Mutant (recessive) allelePurple 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
Consider, for example, the traits that Mendel studied
Another example is from Drosophila
Wild-type (dominant) allele Mutant (recessive) alleleRed eyes White eyes
Normal wings Miniature wings
Human genetic diseases caused by recessive mutant alleles The mutant alleles do not produce fully
functional proteins
Extended Mendelian Inheritance Patterns
Incomplete dominance Heterozygosity at a locus produces a third 3 phenotype
intermediate to the two homozygous phenotypes Co-dominance
Heterozygosity at a locus produces a single unique phenotype different from either homozygous condition
Overdominance Heterozygosity at a locus creates a phenotype that is more
beneficial or more deterimental than homozygosity of either locus with any allele
Lethality Homozygosity of an allele kills the cell or organism
Penetrance 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
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Extended Mendelian Inheritance Patterns
Sex-linked inheritance of genes on that are unique to a sex
chromosomes pseudoautosomal genes – genes on both sex chromosomes
appear to be on autosomes Sex-influenced
An allele is expressed differently in each sex. Behaving dominantly in one sex and recessively in the other
Sex-limited An allele is only expressed in one or the other sex
recessive allele does not affect the phenotype of the heterozygote
two possible explanations 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
The heterozygote may actually produce more than 50% of the functional protein
Complete Dominance/Recessiveness
Simple Mendelian Inheritance
Figure 4.1
Lethal Alleles Essential genes are those that are absolutely
required for survival The absence of their protein product leads to a lethal
phenotype 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 These alleles are typically the result of mutations in
essential genes usually recessive, but can be dominant
Many lethal alleles prevent cell division
Some lethal allele exert their effect later in life Huntington disease
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 Temperature-sensitive (ts) lethals
A developing Drosophila larva may be killed at 30 C But it will survive if grown at 22 C
Lethal Alleles
Semilethal alleles 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 Creepers have shortened legs and must creep along Such birds also have shortened wings
Creeper chicken are heterozygous
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Phenotypic Ratios Associated with Lethal Alleles
Creeper X Normal
1 creeper : 1 normal
Creeper is a dominant allele
Creeper X Creeper
1 normal : 2 creeper
Creeper is lethal in the homozygous state
Incomplete Dominance
heterozygote exhibits a phenotype intermediate to the homozygotes
Also called intermediate dominance or dosage effect
Example: Flower color in the four o’clock plant governed
by 2 alleles CR = wild-type allele for red flower color CW = allele for white flower color
Incomplete Dominance
Figure 4.2
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
complete or incomplete dominance can depend on level of examination
Incomplete Dominance
Alleles of white – 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
Gene Dosage – A form of intermediate dominance
eosin ♀ and eosin ♂ phenotypes
Morgan & Bridges hypothesized that difference in intensity was due to the difference in number of X chromosomes Female has two copies of the “eosin color
producer” allele Eyes will contain more color
Males have only one copy of the allele Eyes will be paler
This is an example of gene dosage effect
Gene Dosage
The term multiple alleles is used to describe situations when three or more different alleles of a gene exist
Examples: ABO blood Coat color in many species Eye color in Drosophila
Multiple Alleles
ABO blood phenotype is determined by multiple alleles
ABO type result of antigen on surface of RBCs Antigen A, which is controlled by allele IA Antigen B, which is controlled by allele IB
Antigen O, which is controlled by allele i
Multiple Alleles
N-acetyl-galactosamine
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
Co-dominance
coat color in rabbits C (full coat color) cch (chinchilla pattern of coat color)
Partial defect in pigmentation ch (himalayan pattern of coat color)
Pigmentation in only certain parts of the body c (albino)
Lack of pigmentation INSERT Figure 4.4
Multiple Alleles
Multiple Alleles
Dominance hierarchy will exist for multiple alleles called an allelic series allelic series for ABO type
IA = IB > i allelic series for rabbit coat color alleles :
C > cch > ch > c allelic series for alleles of white gene
W+/_ > we/we > we/w > w/w = w/Y
The ch allele is a temperature-sensitive conditional mutant The enzyme is only functional at low
temperatures Therefore, dark fur will only occur in cooler areas
of the body
Conditional Mutations
Overdominance is the phenomenon in which a heterozygote is more vigorous than both of the corresponding homozygotes
Example: Sickle-cell heterozygotes are resistant to malaria increased disease resistance in plant hybrids
Overdominance
In some instances, a dominant allele is not expressed in a heterozygote individual
Example = Polydactyly 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
Incomplete Penetrance
Inherited the polydactyly allele from his mother and passed it
on to a daughter and son
Figure 4.11
Does not exhibit the trait himself even though he is a heterozygote
The term indicates that a dominant allele does not always “penetrate” into the phenotype of the individual
The measure of penetrance is described at the population level If 60% of heterozygotes carrying a dominant allele
exhibit the trait allele, the trait is 60% penetrant Note:
In any particular individual, the trait is either penetrant or not
Incomplete Penetrance
Expressivity is the degree to which a trait is expressed
In the case of polydactyly, the number of extra digits can vary A person with several extra digits has high expressivity
of this trait A person with a single extra digit has low expressivity
Expressivity
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 Environment
and/or Other genes (genetic background)
Penetrance & Expressivity