1. Simple Mendelian inheritance involves
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

2. 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

3. Consider, for example, the traits that Mendel studied
Wild-type (dominant) allele
Mutant (recessive) allele
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. Human genetic diseases caused by recessive mutant alleles
The mutant alleles do not produce fully functional proteins

5. 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

6. 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
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7. Complete Dominance/Recessiveness
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

8. Simple Mendelian Inheritance
Figure 4.1

9. 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

10. Lethal Alleles 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

11. An example is the “creeper” allele in chicken
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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12. Phenotypic Ratios Associated with Lethal Alleles
Creeper X Normal
Creeper X Creeper
1 creeper : 1 normal
1 normal : 2 creeper
Creeper is lethal in the
homozygous state
Creeper is a dominant allele

13. 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

14. Incomplete Dominance

15. 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

16. Incomplete Dominance
complete or incomplete dominance can depend on level of examination

17. Gene Dosage – A form of intermediate 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

18. eosin ♀ and eosin ♂ phenotypes

19. This is an example of gene dosage effect
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

20. Multiple Alleles
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

21. 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
N-acetyl-
galactosamine

22. Co-dominance 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

23. Multiple Alleles 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

25. 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

26. Conditional Mutations
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

27. Overdominance
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

28. Incomplete Penetrance
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

29. 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

30. Incomplete Penetrance
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

31. Expressivity 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

32. Penetrance & 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)