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