3.4 Inheritance

Question 1

Who is Gregor Mendel and what did he develop?

Answer 1

Gregor Mendel was an Austrian monk who developed the principles of inheritance by performing experiments on pea plants

Question 2

How did he develop the principles of inheritance? What did he find?

Answer 2

• Experimented 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)

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-fertilised 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 conclusion did Mendel draw from his experiments?

Answer 3

• Organisms have discrete factors that determine its features (these ‘factors’ are now recognised as genes)
• Furthermore, organisms possess two versions of each factor (these ‘versions’ are now recognised as alleles)
• Each gamete contains only one version of each factor (sex cells are now recognised 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

What are 3 rules of inheritance?

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 to 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

What are gametes?

Answer 5

Gametes are haploid sex cells formed by the process of meiosis – males produce sperm and females produce ova

Question 6

How many allele do gametes possess for each gene? How many does the resulting zygote have after the male and female gametes fuse during fertilisation? What is an exception?

Answer 6

Gametes are haploid, meaning they only possess one allele for each gene

When male and female gametes fuse during fertilisation, 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 7

What are the different combinations of alleles for any given gene?

Answer 7

• 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 8

What is a genotype and phenotype?

Answer 8

The gene composition (i.e. allele combination) for a specific trait is referred to as the genotype

• The genotype of a particular gene will typically be either homozygous or heterozygous

The observable characteristics of a specific trait (i.e. the physical expression) is referred to as the phenotype

• The phenotype is determined by both the genotype and environmental influences

Question 9

When would the recessive allele be expressed in the phenotype?

Answer 9

When in a homozygous state

Question 10

When does co-dominance occur?

Answer 10

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 are having a joint effect

Question 11

How is a co-dominant allele represented?

Answer 11

Using superscripts for different co-dominant alleles (recessive still lower case)

Question 12

How are human red blood cells categorised?

Answer 12

Human red blood cells can be categorised into different blood groups based on the structure of a surface glycoprotein (antigen)

Question 13

Are A,B,O dominant, codominant, or recessive

Answer 13

• The A and B alleles are co-dominant and each modify the structure of the antigen to produce different variants
• The O allele is recessive and does not modify the basic antigenic structure

Question 14

What do A,B and O alleles all produce?

Answer 14

The A, B and O alleles all produce a basic antigen on the surface of red blood cells

Question 15

What cant and can A,B,AB,O blood receive?

Answer 15

Question 16

What is the consequence of an Incompatible blood transfusion?

Answer 16

Surface antigens on a incompatible blood cell will be attacked by antibodies from your body = Agglutination (clumping) then Haemolysis

Question 17

How are genetic diseases caused?

Answer 17

Genetic diseases are caused when mutations to a gene (or genes) 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 18

When will an autosomal recessive genetic disease occur? An example?

Answer 18

An autosomal recessive genetic disease will only occur 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 19

When will an autosomal dominant genetic disease occur? An example?

Answer 19

An autosomal dominant genetic disease only requires 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 20

How many copy of the faulty allele is needed to have a genetic disease caused by co-dominant alleles? What is the effect on heterozygous individuals? An example?

Answer 20

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 anaemia

Question 21

What is cystic fibrosis? Who will develop, who are carriers?

Answer 21

• Cystic fibrosis is an autosomal recessive disorder caused by a mutation to the CFTR gene on chromosome 7
• Individuals with cystic fibrosis produce mucus which 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 22

What is Huntington’s disease?

Answer 22

• 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 is unstable and causes 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 23

How common are recessive and dominant conditions?

Answer 23

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 24

What does sex linkage mean in genetic diseases? An example?

Answer 24

Sex linkage refers to when a gene controlling a characteristic is located on a sex chromosome (X or Y)

Haemophilia A and Colour blindness

Question 25

Why are sex-linked conditions usually X-linked?

Answer 25

* 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 26

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

Answer 26

Sex-linked inheritance patterns differ from autosomal patterns due to the fact that the chromosomes aren’t paired in males (XY) * This leads to the expression of sex-linked traits being predominantly associated with a particularly gender

Question 27

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

Answer 27

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) 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 28

What does hemizygous mean?

Answer 28

An individual who has only one member of a chromosome pair or gene rather than the usual two ex. men and their X Y chromosome (are different so they dont pair up). For X-linked genes, they cannot be heterozygous or homozygous

Question 29

What are 3 trends that are always true for X-linked conditions?

Answer 29

* 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 30

Why is red-green colour blindness and haemophilia more common in males?

Answer 30

Red-green colour blindness and haemophilia are both examples of X-linked recessive conditions * Consequently, they are both far more common in males than in females (males cannot mask the trait as a carrier)

Question 31

What is the convention for assigning alleles for a sex-linked trait?

Answer 31

When assigning alleles for a sex-linked trait, 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 32

What is Haemophilia?

Answer 32

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 33

What is Red-green colour blindness?

Answer 33

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 34

What causes gene mutations? What are some factors that can induce mutations? What are mutagens?

Answer 34

* Mutations can be *spontaneous* (caused by copying errors during DNA replication) or *induced* by exposure to external elements * **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) Mutagens are agents which increase the rate of genetic mutations and can lead to the formation of genetic diseases

Question 35

What are the mutagens that lead to the formation of cancer called?

Answer 35

Carcinogens

Question 36

What happened at Hiroshima and Chernombyl? What were the consequences?

Answer 36

Both released a lot of radiation Hiroshima: Nuclear bombing released, more people died Chernombyl: Explosion at the reactor core caused the release of radioactive material, more radiation Some of the long-term consequences of radiation exposure following these disasters include: * An increased incidence in cancer development (with a strong correlation between dose of radiation and 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 37

What is a pedigree?

Answer 37

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

Question 38

How are women+men, affected+unaffected, mating+offsprings, generations represented?

Answer 38

* 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 39

How to determine an autosomal dominant condition from a pedigree?

Answer 39

* 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 40

How to determine an autosomal recessive condition from a pedigree?

Answer 40

* 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 41

Can you determine X-Linked inheritance from pedigree charts?

Answer 41

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 42

How to determine X-linked dominant condition from pedigree?

Answer 42

* 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 43

How to determine an X-linked recessive condition form a pedigree chart?

Answer 43

* 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)