3.4 Inheritance

Question 1

Describe how Mendel made his discoveries

Answer 1

• Gregor Mendel was an Austrian monk who developed the principles of inheritance by performing experiments on pea plants
• First, he crossed different varieties of purebred pea plants, then collected and grew the seeds to determine their characteristics
• Next, he crossed the offspring with each other (self-fertilization) and grew their seeds to similarly determine their characteristics
• These crosses were performed many times to establish reliable data trends (over 5,000 crosses were performed)

Question 2

What did Mendel discover as a result of his experiments?

Answer 2

1. When he crossed two different purebred varieties together the results were not a blend – only one feature would be expressed
   - E.g. When purebred tall and short pea plants were crossed, all offspring developed into tall growing plants
2. When Mendel self-fertilized the offspring, the resulting progeny expressed the two different traits in a ratio of ~ 3:1
   - E.g. When the tall growing progeny were crossed, tall and short pea plants were produced in a ratio of ~ 3:1

Question 3

What conclusions did Mendel make based on his findings?

Answer 3

• Organisms have discrete factors that determine their features (these ‘factors’ are now recognized as genes)
• Furthermore, organisms possess two versions of each factor (these ‘versions’ are now recognized as alleles)
• Each gamete contains only one version of each factor (sex cells are now recognized to be haploid)
• Parents contribute equally to the inheritance of offspring as a result of the fusion between randomly selected egg and sperm
• For each factor, one version is dominant over another and will be completely expressed if present

Question 4

While there are caveats to Mendel’s conclusions, certain rules can be established. What are these?

Answer 4

1. Law of Segregation: When gametes form, alleles are separated so that each gamete carries only one allele for each gene
2. Law of Independent Assortment: The segregation of alleles for one gene occurs independently of that of any other gene*
3. Principle of Dominance: Recessive alleles will be masked by dominant alleles†

*The law of independent assortment does not hold true for genes located on the same chromosome (i.e. linked genes)

† Not all genes show a complete dominance hierarchy – some genes show co-dominance or incomplete dominance

Question 5

Diagram showing Mendel’s garden pea plant experiment

Answer 5

Question 6

What are gametes and how are they produced?

Answer 6

• Gametes are haploid sex cells formed by the process of meiosis – males produce sperm and females produce ova
• During meiosis I, homologous chromosomes are separated into different nuclei before cell division
• As homologous chromosomes carry the same genes, segregation of the chromosomes also separates the allele pairs
• Consequently, as gametes contain only one copy of each chromosome they, therefore, carry only one allele of each gene

Question 7

Diagram showing male vs. female gametes

Answer 7

Question 8

What is the significance of the fact that gametes are haploid?

Answer 8

• Gametes are haploid, meaning they only possess one allele for each gene
• When male and female gametes fuse during fertilization, the resulting zygote will contain two alleles for each gene
• Exception: Males have only one allele for each gene located on a sex chromosome, as these chromosomes aren’t paired (XY)

Question 9

How can the combination of alleles for any given gene be categorized?

Answer 9

• If the maternal and paternal alleles are the same, the offspring is said to be homozygous for that gene
• If the maternal and paternal alleles are different, the offspring is said to be heterozygous for that gene
• Males only have one allele for each gene located on a sex chromosome and are said to be hemizygous for that gene

Question 10

Diagram showing the types of zygosity

Answer 10

Question 11

What is the genotype?

Answer 11

• The gene composition (i.e. allele combination) for a specific trait
• The genotype of a particular gene will typically be either homozygous or heterozygous

Question 12

What is the phenotype?

Answer 12

• The observable characteristics of a specific trait (i.e. the physical expression)
• The phenotype is determined by both the genotype and environmental influences

Question 13

Complete dominance

Answer 13

• Most traits follow a classical dominant/recessive pattern of inheritance, whereby one allele is expressed over the other
• The dominant allele will mask the recessive allele when in a heterozygous state
• Homozygous dominant and heterozygous forms will be phenotypically indistinguishable
• The recessive allele will only be expressed in the phenotype when in a homozygous state
• When representing alleles, the convention is to capitalize the dominant allele and use a lowercase letter for the recessive allele
• An example of this mode of inheritance is mouse coat color – black coats (BB or Bb) are dominant to brown coats (bb)

Question 14

Diagram of complete dominance (mouse coat color)

Answer 14

Question 15

Co-dominance

Answer 15

• Co-dominance occurs when pairs of alleles are both expressed equally in the phenotype of a heterozygous individual
• Heterozygotes, therefore, have an altered phenotype as the alleles have a joint effect
• When representing alleles, the convention is to use superscripts for the different co-dominant alleles (recessive still lower case)
• An example of co-dominance is feathering in chickens – black (C^B) and white (C^W) feathers create a speckled coat (C^BC^W)

Question 16

Diagram of co-dominance (chicken feathering)

Answer 16

Question 17

How can human red blood cells be categorized?

Answer 17

• They can be categorized into different blood groups based on the structure of a surface glycoprotein (antigen)
• The ABO blood groups are controlled by a single gene with multiple alleles (A, B, O)
• The A, B, and O alleles all produce a basic antigen on the surface of red blood cells
• The A and B alleles are co-dominant and each modifies the structure of the antigen to produce different variants
• The O allele is recessive and does not modify the basic antigenic structure

Question 18

What is the letter I used for when representing blood group alleles?

Answer 18

To represent the different antigenic forms (isoantigens)

A allele = I^A ; B allele = I^B ; O allele = i (recessive)

Question 19

Table summarizing the genotypes for the different blood groups

Answer 19

Question 20

Explain why blood transfusions are not compatible between certain blood groups

Answer 20

• As humans produce antibodies against foreign antigens, blood transfusions are not compatible between certain blood groups
• AB blood groups can receive blood from any other type (as they already possess both antigenic variants on their cells)
• A blood groups cannot receive B blood or AB blood (as the isoantigen produced by the B allele is foreign)
• B blood groups cannot receive A blood or AB blood (as the isoantigen produced by the A allele is foreign)
• O blood groups can only receive transfusions from other O blood donors (both antigenic variants are foreign)

Question 21

Summary table of the ABO blood groups

Answer 21

Question 22

Diagram showing the consequence of incompatible blood transfusion

Answer 22

Question 23

Steps of drawing monohybrid crosses

Answer 23

• A monohybrid cross determines the allele combinations for potential offspring for one gene only
• Monohybrid crosses can be calculated according to the following steps:
• Step 1: Designate letters to represent alleles (dominant = capital letter ; recessive = lower case ; co-dominant = superscript)
• Step 2: Write down the genotype and phenotype of the prospective parents (this is the P generation)
• Step 3: Write down the genotype of the parental gametes (these will be haploid and thus consist of a single allele each)
• Step 4: Draw a grid with maternal gametes along the top and paternal gametes along the left (this is a Punnett grid)
• Step 5: Complete the Punnett grid to determine potential genotypes and phenotypes of offspring (this is the F1 generation)

Question 24

Diagram showing an overview of a monohybrid cross

Answer 24

Question 25

Comparison of predicted and actual outcomes of genetic crosses using real data

Answer 25

- The genotypic and phenotypic ratios calculated via Punnett grids are only probabilities and may not always reflect actual trends - E.g. When flipping a coin there is a 50% chance of landing on heads – this doesn’t mean you will land on heads 50% of the time - When comparing predicted outcomes to actual data, larger data sets are more likely to yield positive correlations - Gregor Mendel performed over 5,000 crosses as part of his pea plant experiment - However, many statisticians believe Mendel’s results are too close to the exact ratios predicted to be genuine

Question 26

Table showing Mendel's pea plant experimental data

Answer 26

Question 27

Methodology of Mendel's pea plant experiments

Answer 27

- Mendel crossed different varieties of pea plants and recorded the characteristics of the resultant offspring - Initially, he crossed purebred dominant and purebred recessive plants to produce heterozygotes (F1 generation) - He then self-pollinated the heterozygotes to produce an F2 generation and counted the dominant and recessive phenotypes - The expected ratio of dominant: recessive phenotypes was 3: 1 – this ratio was supported by the experimental data

Question 28

What causes genetic diseases?

Answer 28

- Mutations to a gene (or genes) that abrogate normal cellular function, leading to the development of a disease phenotype - Genetic diseases can be caused by recessive, dominant, or co-dominant alleles

Question 29

When will an autosomal recessive genetic disease only occur?

Answer 29

- If both alleles are faulty - Heterozygous individuals will possess one copy of the faulty allele but not develop disease symptoms (they are carriers) - An example of an autosomal recessive genetic disease is cystic fibrosis

Question 30

Autosomal dominant genetic diseases

Answer 30

- These only require one copy of a faulty allele to cause the disorder - Homozygous dominant and heterozygous individuals will both develop the full range of disease symptoms - An example of an autosomal dominant genetic disease is Huntington’s disease

Question 31

Genetic diseases caused by co-dominant alleles

Answer 31

- If a genetic disease is caused by co-dominant alleles, it will also only require one copy of the faulty allele to occur - However, heterozygous individuals will have milder symptoms due to the moderating influence of a normal allele - An example of a genetic disease that displays co-dominance is sickle cell anemia

Question 32

Diagram showing inheritance patterns for dominant and recessive genetic disorders

Answer 32

Question 33

Cystic fibrosis

Answer 33

- Cystic fibrosis is an autosomal recessive disorder caused by a mutation to the CFTR gene on chromosome 7 - Individuals with cystic fibrosis produce mucus that is unusually thick and sticky - This mucus clogs the airways and secretory ducts of the digestive system, leading to respiratory failure and pancreatic cysts - Heterozygous carriers who possess one normal allele will not develop disease symptoms

Question 34

Diagram of chest X-rays for people without and with cystic fibrosis

Answer 34

Question 35

Huntington's disease

Answer 35

- Huntington’s disease is an autosomal dominant disorder caused by a mutation to the Huntingtin (HTT) gene on chromosome 4 - The HTT gene possesses a repeating trinucleotide sequence (CAG) that is usually present in low amounts (10 – 25 repeats) - More than 28 CAG repeats are unstable and cause the sequence to amplify (produce even more repeats) - When the number of repeats exceeds ~40, the huntingtin protein will misfold and cause neurodegeneration - This usually occurs in late adulthood and so symptoms usually develop noticeably in a person’s middle age (~40 years) - Symptoms of Huntington’s disease include uncontrollable, spasmodic movements (chorea) and dementia

Question 36

Diagram of proteins and brains of people without and with Huntington's disease

Answer 36

Question 37

Identification of genetic diseases in humans

Answer 37

- There are over 4,000 identified single gene defects that lead to genetic disease, but most are very rare - Any allele that adversely affects survival and hence the capacity to reproduce is unlikely to be passed on to offspring - Recessive conditions tend to be more common, as the faulty allele can be present in carriers without causing disease - Dominant conditions may often have a late onset, as this does not prevent reproduction and the transfer of the faulty allele

Question 38

What is sex linkage?

Answer 38

- When a gene controlling a characteristic is located on a sex chromosome (X or Y) - The Y chromosome is much shorter than the X chromosome and contains only a few genes (50 million bp; 78 genes) - The X chromosome is longer and contains many genes not present on the Y chromosomes (153 million bp; ~ 2,000 genes) - Hence, sex-linked conditions are usually X-linked - as very few genes exist on the shorter Y chromosome

Question 39

Diagram of X and Y chromosomes

Answer 39

Question 40

Why do sex-linked inheritance patterns differ from autosomal patterns?

Answer 40

- Because chromosomes aren’t paired in males (XY) - This leads to the expression of sex-linked traits being predominantly associated with a particular gender

Question 41

Why are X-linked dominant traits more common in females?

Answer 41

- As human females have two X chromosomes (and therefore two alleles), they can be either homozygous or heterozygous - Hence, X-linked dominant traits are more common in females (as either allele may be dominant and cause disease)

Question 42

Why are X-linked recessive traits more common in males?

Answer 42

- Human males have only one X chromosome (and therefore only one allele) and are hemizygous for X-linked traits - X-linked recessive traits are more common in males, as the condition cannot be masked by a second allele

Question 43

What trends hold true for X-linked conditions?

Answer 43

- Only females can be carriers (a heterozygote for a recessive disease condition), males cannot be heterozygous carriers - Males will always inherit an X-linked trait from their mother (they inherit a Y chromosome from their father) - Females cannot inherit an X-linked recessive condition from an unaffected father (must receive his dominant allele)

Question 44

Diagram showing inheritance of an X-linked recessive disease condition

Answer 44

Question 45

What are red-green color-blindness and hemophilia examples of?

Answer 45

- Sex-linked inheritance/ X-linked recessive inheritance - Consequently, they are both far more common in males than in females (males cannot mask the trait as a carrier)

Question 46

Conventions for assigning alleles for a sex-linked trait

Answer 46

- The convention is to write the allele as a superscript to the sex chromosome (X) - Haemophilia: X^H = unaffected (normal blood clotting) ; X^h = affected (haemophilia) - Colour blindness: X^A = unaffected (normal vision) ; X^a = affected (colour blindness)

Question 47

Hemophilia

Answer 47

- Haemophilia is a genetic disorder whereby the body’s ability to control blood clotting (and hence stop bleeding) is impaired - The formation of a blood clot is controlled by a cascade of coagulation factors whose genes are located on the X chromosome - When one of these factors becomes defective, fibrin formation is prevented - meaning bleeding continues for a long time - Different forms of haemophilia can occur, based on which specific coagulation factor is mutated (e.g. haemophilia A = factor VIII)

Question 48

Red-green color blindness

Answer 48

- Red-green colour blindness is a genetic disorder whereby an individual fails to discriminate between red and green hues - This condition is caused by a mutation to the red or green retinal photoreceptors, which are located on the X chromosome - Red-green colour blindness can be diagnosed using the Ishihara colour test

Question 49

What is a gene mutation?

Answer 49

A change to the base sequence of a gene that can affect the structure and function of the protein it encodes

Question 50

How can mutations arise?

Answer 50

They can be spontaneous (caused by copying errors during DNA replication) or induced by exposure to external elements

Question 51

Examples of factors that induce mutations

Answer 51

- Radiation – e.g. UV radiation from the sun, gamma radiation from radioisotopes, X-rays from medical equipment - Chemical – e.g. reactive oxygen species (found in pollutants), alkylating agents (found in cigarettes) - Biological Agents – e.g. bacteria (such as Helicobacter pylori), viruses (such as human papilloma virus)

Question 52

What are mutagens?

Answer 52

- Agents that increase the rate of genetic mutations - They can lead to the formation of genetic diseases

Question 53

What are carcinogens?

Answer 53

Mutagens that lead to the formation of cancer

Question 54

Diagram showing types of mutagens

Answer 54

Question 55

Nuclear bombings of Hiroshima and the accident at Chernobyl

Answer 55

- These are two examples of a catastrophic release of radioactive material - The nuclear bombing of Hiroshima (and Nagasaki) occurred in August 1945, during the final stages of World War II - The Chernobyl accident occurred in April 1986, when an explosion at the reactor core caused the release of radioactive material - Of the two incidents, more people died from the nuclear bombing, but the meltdown released far more radiation (~400×) - The Chernobyl meltdown involved far more fissionable material and produced different isotopes with much longer half-lives - The Hiroshima nuclear bomb was detonated above ground and radiation was dispersed, resulting in less irradiation of the soil

Question 56

Long-term consequences of radiation exposure following Hiroshima and Chernobyl

Answer 56

- An increased incidence of cancer development (with a strong correlation between the dose of radiation and the frequency of cancer) - Reduced T cell counts and altered immune functions, leading to higher rates of infection - A wide variety of organ-specific health effects (e.g. liver cirrhosis, cataract induction, etc.) - Some of the consequences of radiation exposure are specific to the incident due to the types and amounts of radiation released - Thyroid disease was a common consequence of the Chernobyl accident due to the release of radioactive iodine - There was no significant increase in birth defects following the Hiroshima bombing, but an estimated 250% increase in congenital abnormalities following the Chernobyl meltdown

Question 57

Are Hiroshima and Chernobyl still habitable?

Answer 57

- While Hiroshima is still habitable and well populated, certain regions of Chernobyl remain unsafe for human habitation - There is anecdotal evidence to suggest that radiation levels around Chernobyl have caused variation to local flora and fauna - The presence of residual radiation in the environment can become concentrated in organisms via bioaccumulation

Question 58

What is a pedigree?

Answer 58

A chart of the genetic history of a family over several generations

Question 59

Describe how pedigree charts are drawn

Answer 59

- Males are represented as squares, while females are represented as circles - Shaded symbols mean an individual is affected by a condition, while an unshaded symbol means they are unaffected - A horizontal line between man and woman represents mating and resulting children are shown as offshoots to this line - Generations are labeled with roman numerals and individuals are numbered according to age (oldest on the left)

Question 60

Determining autosomal inheritance

Answer 60

Dominant and recessive disease conditions may be identified only if certain patterns occur (otherwise it cannot be confirmed)

Question 61

Determining autosomal inheritance- autosomal dominant

Answer 61

- If both parents are affected and an offspring is unaffected, the trait must be dominant (parents are both heterozygous) - All affected individuals must have at least one affected parent - If both parents are unaffected, all offspring must be unaffected (homozygous recessive)

Question 62

Determining autosomal inheritance- autosomal recessive

Answer 62

- If both parents are unaffected and an offspring is affected, the trait must be recessive (parents are heterozygous carriers) - If both parents show a trait, all offspring must also exhibit the trait (homozygous recessive)

Question 63

Determining X-Linked inheritance

Answer 63

- It is not possible to confirm sex linkage from pedigree charts, as autosomal traits could potentially generate the same results - However, certain trends can be used to confirm that a trait is not X-linked dominant or recessive

Question 64

Determining X-Linked inheritance- X-linked dominant

Answer 64

- If a male shows a trait, so too must all daughters as well as his mother - An unaffected mother cannot have affected sons (or an affected father) - X-linked dominant traits tend to be more common in females (this is not sufficient evidence though)

Question 65

Determining X-Linked inheritance- X-linked recessive

Answer 65

- If a female shows a trait, so too must all sons as well as her father - An unaffected mother can have affected sons if she is a carrier (heterozygous) - X-linked recessive traits tend to be more common in males (this is not sufficient evidence though)

Question 66

Incomplete dominance

Answer 66

- Sometimes, when two alleles are present in an individual, the phenotype is different than in either homozygous state. - This is incomplete dominance, where neither of the two alleles is dominant, and both impact the phenotype. - The notation for co-dominant alleles is a capital letter (indicating the trait) with a capital superscript (indicating the allele). - For example, snapdragons show incomplete dominance for flower color. - C^R is the allele for red flowers while C^W is the allele for white. - A plant will have red flowers if it has the genotype C^RC^R and white flowers if the genotype is C^WC^W. - However, if its genotype is C^RC^W, it will have pink flowers (a blend of red and white).