Chapter 4: Extensions of Mendelian Inheritance

What are two Mendelian Inheritance laws that Mendelian Inheritance describes inheritance patterns?

1. Law of Segregation

2. Law of Independent Assortment

What does Simple Mendelian Inheritance involve?

1. A single gene with two different alleles

2. Alleles display a simple dominant/recessive relationship

Inheritance definition of Simple Mendelian Inheritance?

This term is commonly applied to the inheritance of alleles that obey Mendel’s laws and follow a strict dominant/recessive relationship. The chapter shows that some genes occur as three of more alleles, making the relationship more complex

Molecular definition of Simple Mendelian Inheritance?

50% of the protein, produced by a single copy of the dominant (functional) allele in the heterozygote, is sufficient to produce the dominant trait

Inheritance definition of Incomplete Penetrance?

In the case of dominant traits, this pattern occurs when a dominant phenotype is not expressed even though an individual carries a dominant allele. An example is an individual who carries the polydactyly allele but has a normal number of fingers and toes. In the case of recessive traits, this pattern occurs when a homozygote carrying both recessive alleles does not exhibit the trait

Molecular definition of Incomplete Penetrance?

Even though a dominant allele is present or two recessive alleles are present, the protein coded by the gene may not exert its effects. This can be due to environmental influences or due to other genes that may code proteins that counteract the effects of the protein coded by the dominant allele

Inheritance definition of Incomplete Dominance?

This pattern occurs when the heterozygote has a phenotype that is intermediate between either corresponding homozygote. For example, a cross between homozygous red-flowered and homozygous white-flowered parents produces heterozygous offspring with pink flowers

Molecular definition of Incomplete Dominance?

50% of the protein, produced by a single copy of the functional allele in the heterozygote, is not sufficient to produce the same trait as in a homozygote making 100% of that protein

Inheritance definition of Heterozygote Advantage?

This pattern occurs when the heterozygote has a trait that confers a greater level of reproductive success than either homozygous has

Molecular definition of Heterozygote Advantage?

Three common ways that heterozygotes may gain benefits

1. Their cells may have increased resistance to infection by microorganisms

2. They may produce more forms of protein dimers with enhanced function

3. They make produce proteins that function under a wider range of conditions

Inheritance definition of Codominance?

This pattern occurs when the heterozygote expresses both alleles simultaneously without forming an intermediate phenotype. For example, with regard to human blood types, an individual carrying the A and B alleles will have an AB blood type

Molecular definition of Codominance?

The codominant alleles code proteins that function slightly differently from each other, and the function of each protein in the heterozygote affects the phenotype uniquely

Inheritance definition of X-linked inheritance?

This pattern involves the inheritance of genes that are located on the X chromosome. In mammals and fruit flies, males have one copy of X-linked genes, whereas females have two copies

Molecular definition of X-linked inheritance?

If a pair of X-linked alleles shows a simple dominant/recessive relationship, 50% of the protein, produced by a single copy of the dominant allele in a heterozygous female, is sufficient to produce the dominant trait. Males have only one copy of X-linked genes and therefore express the copy they carry

Inheritance definition of Sex-influenced inheritance?

This pattern refers to the effect of sex on the phenotype of the individual. Some alleles are recessive in males and dominant in females; others are dominant in males and recessive in females

Molecular definition of Sex-influenced inheritance?

Sex hormones may regulate the molecular expression of genes. This regulation can influence the phenotypic effects of alleles

Inheritance definition of Sex-limited Inheritance?

In this pattern, a trait occurs in only one sex. It may occur in males or females, but not both. An example is sperm production in male animals.

Molecular definition of Sex-limited Inheritance?

Sex hormones may regulate the molecular expression of genes. This regulation can influence the phenotypic effects of alleles. In this pattern of inheritance, sex hormones that are primarily produced in only one sex are essential for an individual to display a particular phenotype

Inheritance definition of Lethal Alleles?

A lethal allele is one that has the potential of causing the death of an organism

Molecular definition of Lethal Alleles?

Lethal alleles are most commonly loss-of-function alleles that code proteins that are necessary for survival. In some cases, such as an allele may be due to a mutation in a nonessential gene that changes a protein so that it functions with abnormal and detrimental consequences

What are the two goals of the patterns in Table 4.1?

1. Predict the outcome of crosses

2. Understand the relationship between the molecular expression of a gene and the trait itself

What are wild-type alleles?

Prevalent alleles in a population

What do wild-type alleles do?

Typically encode proteins

What is the function of encoding proteins for wild-type alleles ?

1. Encode proteins that function normally

2. Encode proteins that are made in the proper amounts

What is Genetic Polymorphism Phenomenon?

More than one wild-type allele may occur in large populations

What are Mutant Alleles?

Alleles that have been altered by mutation

What are three facts of Mutant Alleles?

1. They are often defective in their ability to express a functional protein

2. These tend to be rare in natural populations

3. Such mutant alleles are often inherited in a recessive fashion

Does the recessive allele affect the phenotype of the heterozygote in a simple dominant/recessive relationship?

No

What are two explanations to explain the wild-type phenotype of a heterozygote?

1. 50% of the normal protein is enough to accomplish the proteins cellular function

2. The heterozygote may actually produce more than 50% of the functional protein

What is the idea about the normal gene and defective allele?

The normal gene is “up-regulated” to compensate for the lack of function of the defective allele

What is an example of protein levels/phenotype in simple dominant/recessive relationship?

Dominant (functional) allele: P (purple)

Recessive (defective) allele: p (white)

PP: 100% functional protein P

Pp: 50% functional protein P

pp: 0% functional protein P

What are Genetic Diseases usually caused by?

Mutant Alleles

In many human genetics diseases, the recessive allele causes a?

Mutation

The recessive allele that causes a mutation prevents what?

Prevents the allele from producing a fully functional protein

What are the alleles for Individuals who exhibit a disease?

Either homozygous for a recessive allele or hemizygous (for x-linked genes in human males)

What does disease symptoms result from?

A defect in the amount of function of the normal protein

What are the 6 Recessive Human Diseases?

1. Phenylketonuria

2. Albinism

3. Tay-Sachs Disease

4. Sandhoff Disease

5. Cystic Fibrosis

6. Lesch-Nyhan Syndrome

What protein is produced by the normal gene in the Phenylketonuria?

Phenylalanine hydroxylase

What protein is produced by the normal gene in the Albinism?

Tyrosinase

What protein is produced by the normal gene in Tay-Sachs Disease?

Hexosaminidase A

What protein is produced by the normal gene in Sandhoff Disease?

Hexosaminidase B

What protein is produced by the normal gene in Cystic Fibrosis?

Chloride transporter

What protein is produced by the normal gene in Lesch-Nyhan Syndrome?

Hypoxanthine-guanine phosphoribosyl transferase

What is Phenylketonuria?

Inability to metabolize phenylalanine. The disease can be prevented by following a phenylalanine-free diet. If the diet is not followed early in life, the result can be severe mental impairment and physical degeneration.

What is Albinism?

Lack of pigmentation in the skin, eyes, and hair.

What is Tay-Sachs Disease?

Defect in lipid metabolism. Leads to paralysis, blindness, and early death

What is Sandhoff Disease?

Defect in lipid metabolism. Muscle weakness in infancy, early blindness, and progressive mental and motor deterioration

What is Cystic Fibrosis?

Inability to regulate ion balance across epithelial cells. Leads to production of thick mucus and results in chronic lung infections, poor weight gain, and organ malfunctions

What is Lesch-Nyhan Syndrome?

Inability to metabolize purines, which are bases found in DNA and RNA. Leads to self-mutilation behavior, poor motor skills, and usually mental impairment and kidney failure.

Are dominant mutants much less common than recessive?

Yes

What are 3 explanations for most dominant mutations?

1. Haploinsufficiency

2. Gain-of-function

3. Dominant-negative

What is Haploinsufficiency?

Mutant is loss-of-function

Heterozygote does not make enough product to give the wild type phenotype

What is gain-of-function?

Protein encoded by the mutant gene is changed so it gains a new or abnormal function

What is Dominant-negative?

Protein encoded by the mutant gene acts antagonistically to the normal protein

In some instances of incomplete penetrance, does a dominant allele influence the outcome of a trait in a heterozygote individual

No, it does not

What is an example of Incomplete Penetrance?

Polydactyly

What is 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

What is Incomplete Penetrance?

A dominant allele does not always “penetrate” into the phenotype of the individual

What is the measured of penetrance described at?

The population level

What is the population level of incomplete penetrance?

If 60% of heterozygotes carrying a dominant allele exhibit the trait, the trait is 60% penetrant

Is it true that in any particular individual, the trait is either present or not for incomplete penetrance?

Yes

What is Expressivity?

The degree to which a trait is expressed

Does the number of digits vary in Polydactyly?

Yes

What is the relationship between expressivity and polydactyly?

A person with several extra digits has high expressivity of this trait

A person with a single extra digit has low expressivity

Is the molecular explanation and incomplete penetrance always understood?

No

What are the two ranges of phenotypes influenced by?

1. Environment

2. Other “modifier” genes

Do environmental conditions have a great impact on the phenotype of the individual?

Yes

What are two examples of Environmental effects on gene expression?

1. Some animals like the artic fox change coat color

2. Humans affected by phenylketonuria (PKU) are unable to metabolize phenylalanine

What is the temperature-sensitive allele in some Animals (Arctic Fox)?

Grayish brown coat color in summer, white in the winter

What are symptoms of Phenylketonuria?

Mental Impairment

Foul-smelling urine

What happens when phenylketonuria is detected early?

Individuals can be fed a restricted diet essentially free of phenylalanine and remain symptom free

What does Geneticist often examine?

A range of conditions when studying the effect of environment on phenotype

Why do Geneticist study range of conditions?

Allows them to see the norm of reaction of the environmental influence on eye facet number

What is Incomplete Dominance?

The heterozygote exhibits a phenotype that is intermediate between the corresponding homozygotes

What is an example of Incomplete Dominance?

Flower color in the four o’clock plant

What are the two alleles in the Flower color in the four o’clock plant?

1. C^R = wild-type allele for red flower color

2. C^W= allele for white flower color

What happened in F1 in the incomplete dominance flower example?

50% of the C^R protein is not sufficient to produce the red phenotype

What happened in F2 in the incomplete dominance flower example?

1:2:1 phenotypic ratio NOT the 3:1 ratio observed in simple mendelian inheritance

What is an example of a trait that is dominant or incompletely dominant?

Characteristic of pea shape

What did Mendel conclude about pea shapes?

RR and Rr genotypes produced round peas

rr genotypes produced wrinkled peas

What did the microscopic examination of round peas reveal?

That not all round peas are the same

What is Phenotype Comparison?

A comparison of phenotype at the macroscopic and microscopic levels

What is the Genotype in the Phenotype Comparison Example (round vs wrinkled)?

Amount of functional (starch-producing) protein

RR: 100%

Rr: 50%

rr: 0%

What is the result of the phenotype in the round vs winkled example using no microscope (simple dominant/recessive relationship)?

Genotype RR: Round

Genotype Rr: Round

Genotype rr: Wrinkled

What is the result of the phenotype in the round vs wrinkled example with microscope (incomplete dominance)?

Heterozygotes look round, but they only have half the amount of starch found in homozygous dominants

Genotype RR: Round

Genotype Rr: Round

Genotype rr: Wrinkled

What is Overdominance (Heterozygote Advantage)?

The phenomenon in which a heterozygote has greater reproductive success compared to both of the corresponding homozygotes

What is an Example of Overdominance?

Sickle-cell disease

How is sickle-cell disease an example of overdominance?

Autosomal recessive disorder

Affected individuals produce abnormal form of hemoglobin

Two alleles:

1. Hb^A —> Encodes the normal hemoglobin, hemoglobin A

2. Hb^S —> Encodes the abnormal hemoglobin, hemoglobin S

What happens to the Hb^SHb^S allele in individuals with red blood cells?

Red blood cells deform into a sickle shape under conditions of low oxygen tension

What are 2 major ramifications when individuals have the abnormal hemoglobin Hb^S?

1. Sickling phenomenon greatly shortens the life span of the red blood cells (anemia results)

2. Odd-shaped cells clump (partial or complete blocks in capillary circulation

Affected individuals tend to have a shorter life span

How does Hb^A Hb^S individuals (heterozygotes) have an “advantage”?

Over Hb^S Hb^S, because they do not suffer from sickle cell disease

Over Hb^A Hb^A, because they are more resistant to malaria

In parts of Africa this allele is most common ___

Hb^S allele found at high frequency in parts of africa where malaria is found

What is Malaria caused by?

Protozoan, Plasmodium

What 2 main parts does the malaria parasite (Plasmodium) undergo its life cycle?

1. One inside the Anopheles mosquito

2. The other inside red blood cells

What happens when heterozygote individuals are infected by Plasmodium?

Red blood cells of heterozygotes are likely to rupture preventing the propagation of the parasite

What is the genotype and phenotype of the Cross between Hb^A Hb^S x Hb^A Hb^S? (Sickle cell disease)

Hb^A Hb^A: unaffected, not malaria-resistant

Hb^A Hb^S: unaffected, malaria-resistant

Hb^A Hb^S: unaffected, malaria-resistant

Hb^S Hb^S: Sickle cell disease

At the molecular level, what is overdominance due to?

Two alleles that produce slightly different proteins

What do the two protein variance produce?

A favorable phenotype in the heterozygote

What are the 3 possible explanations for overdominance at the molecular/cellular level?

1. Disease resistance

2. Homodimer formation

3. Variation in functional activity

When will a microorganism infect a cell?

If certain cellular proteins function optimally