GENETIC ENGINEERING

Genetics

Q1 Meiosis

• Fig. 4.1 shows an animal cell undergoing meiosis
• Need to identify the stage of meiosis shown in the figure
• It is necessary to describe the main events to complete meiosis from this stage
• Need to describe two ways in which meiosis leads to variation

Q2 Meiosis

• Requires stating the stage of meiosis shown in Fig. 2.1
• Need to describe what has occurred between the two homologous chromosomes
• Requires explanation of how this event can lead to variation
• Two other sources of variation that are possible as a result of meiosis are needed

Q3 Phenotype and Genotype

• Requires distinction between phenotype and genotype
• Requires description of how artificial selection differs from natural selection
• Definitions are needed for the terms "gene" and "allele"

Q3 Cat coat color

• Coat colour in cats is determined by a sex-linked gene with two alleles, black and orange
• When black cats are mated with orange cats, the female offspring are always tortoiseshell
• Their coats show black and orange patches of various sizes
• Male offspring have the same coat colour as their mothers
• Using the symbols XB for black and Xº for orange, genetic diagrams to account for both these crosses are needed

Q4 Genotypes and Phenotypes

• Listing the genotypes and their phenotypes of the offspring that may result from mating a tortoiseshell female with a black male is required
• An explanation is needed for the tortoiseshell coat in terms of the activity of the X chromosomes

Q5 Summer Squash Plant

• The summer squash plant produces fruit that are either white or yellow in colour and are either shaped like a disc or a sphere
• The dominant phenotypes are white and disc shaped fruit
• Using the symbols A for white and a for yellow and B for disc and b for sphere, a genetic diagram to show what proportion of offspring will have yellow and sphere-shaped fruit if a white and disc shaped fruit plant, heterozygous for both genes, is self fertilised is necessary

Q6 Sickle Cell Anaemia

• Sickle cell anaemia is a blood disease that is frequently fatal when homozygous
• It is caused by an autosomal recessive allele
• Heterozygotes have sickle cell trait and appear normal
• Malaria is a potentially fatal infectious disease of the blood caused by the protoctist, Plasmodium
• In parts of the world where malaria is endemic, the frequency of the sickle cell allele is high
• Explanation is needed of the possible health consequences, in such areas, for a person who is homozygous dominant and for a person who is homozygous recessive for the sickle cell allele
• Requires explaining why heterozygotes have a strong selective advantage in areas where malaria occurs

Q7 Multiple Alleles and Codominance

• Sometimes a gene has more than two alleles, termed multiple alleles
• The ABO blood group system in humans is controlled by a gene with three alleles, IA, IB and Iº
• Alleles IA and IB are codominant and Iº is recessive to both
• The blood group AB is the result of codominance
• Requires explaining what is meant by codominance

Q7 Haemophilia

• In humans, a gene that codes for the production of a protein, called factor VIII, is located on the X chromosome
• The dominant allele for this gene produces factor VIII, but the recessive allele does not produce factor VIII
• A person who is unable to make factor VIII has haemophilia in which the blood fails to clot properly
• Explanation is needed as to why a man with haemophilia cannot pass haemophilia to his son but may pass haemophilia to his grandson

Q8 Chicken Feather Colour

• A gene for feather colour in chickens is carried on an autosome
• This gene has two alleles, black (CB) and splashed-white (CW)
• When a male chicken with black feathers is mated with a female chicken with splashed-white feathers, all the offspring have blue feathers
• This also occurs when a male chicken with splashed-white feathers is crossed with a female with black feathers
• Another gene may cause stripes on feathers (barred feathers)
• This gene is carried on the X chromosome
• The allele for barred feathers (XA) is dominant to the allele for non-barred feathers (Xa)
• In chickens the male is homogametic and has two X chromosomes while the female is heterogametic and has one X chromosome and one Y chromosome

Q8 Genetic Diagram for Chicken Feather Colour

• A male chicken with black, non-barred feathers was crossed with a female chicken with splashed-white, barred feathers
• All the offspring had blue feathers, but the males were barred and the females were non-barred
• Using the symbols given above draw a genetic diagram to show this cross
• Explanation is needed as to how a farmer could use a breeding programme to find out the genotype of a male chicken with blue, barred feathers

Q6 Colour Blindness

• Colour blindness is a condition characterised by the inability of the brain to perceive certain colours accurately
• The most common form is termed red-green colour blindness (RGC)
• RGC results from a recessive allele
• 0.6% of females worldwide have RGC
• 8.0% of males worldwide have RGC
• Need to explain the meaning of the terms allele and recessive
• Requires explaining why females are less likely than males to have RGC

Q8 Individual Genotypes

• With reference to Fig. 6.1, and using the symbols R for the dominant allele and r for the recessive allele, state the genotypes of the individuals 1, 4, 6 and 7

Q8 Horse Coat Colour

• The inheritance of coat colour in horses is complex but all horses have one of two base colours, red (chestnut) or black
• The base colour is controlled in a simple monohybrid way
• When chestnut stallions and mares are mated the foals are always chestnut
• When black stallions are mated with black mares, either black or chestnut foals may be produced
• Draw a genetic diagram to show how two parents with black coat colour can produce a chestnut foal and the probability of such an event occurring
• Choose a letter symbol to represent coat colour

Q8 Horse coat genetics

• Five other genes can modify the base coat colour
• One of these genes is the C gene
• There are two alleles of this gene, C and CCR
• C does not affect the base coat colour
• CCR may modify the base coat colour
  • If a chestnut horse has at least one CCR allele its phenotype will be palomino, which is a light cream colour
  • If a black horse has at least one CCR allele its effect will not be noticeable in the phenotype

Q9 Gene mutation and Rickets

• Explanation is needed regarding what is meant by the term gene mutation
• Rickets is a childhood disorder involving the softening and weakening of bones
• it is usually caused by a lack of vitamin D, calcium ions or phosphate ions
• A rare form of rickets that cannot be successfully treated with vitamin D therapy is caused by a mutant allele on the X chromosome
• The gene in which this mutation occurs codes for a protein found in the cells of the proximal convoluted tubule of the kidney
• This protein is involved in phosphate ion transport across membranes
• Suggest why individuals with this mutant allele show symptoms of rickets
• Need to using pedigree charts and appropriate symbols, state the genotypes of different individuals

Q10 Sex Linkage and Cleft Iris

• In humans a rare, sex-linked, recessive allele results in a change in the shape of the iris in the eye
• This condition is know as cleft iris (CI)
• Explanation is needed regarding what is meant by the term sex linkage
• Requires completing the genetic diagram using suitable symbols
• A woman who is heterozygous for CI becomes pregnant by a man with a normal iris, and stating the probability that their child will have CI

Q11 Enzymatic Specifity and Canavan Disease

• Canavan disease is a non sex linked inherited condition that causes progressive damage to neurones of the brain
• Symptoms of the condition include a loss of motor skills and mental retardation
  • The symptoms appear in early infancy and many children with this condition die by the age of four years
• People with Canavan disease lack an enzyme called aspartoacylase which breaks down N acetyl aspartate
• The build up of N acetyl aspartate can interfere with the formation of the myelin sheath, particularly in neurones of the brain Explanation is needed of what is meant by specificity of an enzyme
• Completion is needed of the genetic diagram below to show how an unaffected man and an unaffected woman could produce a child with Canavan disease
• Explanation is necessary regarding the importance of the myelin sheath in the functioning of a neurone

Q12 Meiosis genetic variation

• Meiosis is a type of nuclear division, which produces gametes for sexual reproduction
• Requires writing the stages of meiosis in the correct order in a table
• Explanation is needed regarding how meiosis can result in genetic variation amongst offspring

Q13 Huntington's Disease

• Huntington’s Disease (HD) is a severe neurological disorder in which symptoms usually appear after the person has reached sexual maturity
• symptoms include memory loss and changes in personality and mood
• HD is caused by a gene mutation on chromosome 4 in which the triplet code CAG is repeated many times
• The resulting allele is dominant
• Explanation is needed of the terms gene mutation and triplet code

Q13 Huntington's Disease Genetic Diagram

• A couple wish to start a family
• The man does not have HD but the woman does have the disease
• The woman's father does not have the disease
• Complete the genetic diagram below to show the probability of the couple's first child having HD

Q14 Fruit Fly Inheritance

• The fruit fly, Drosophila melanogaster, has many phenotypic variations and has been used in experiments to demonstrate the principles of inheritance
• The majority of fruit flies have red eyes but there is a variant with white eyes, and the gene for eye colour is located on the X chromosome
• Using suitable symbols, draw a genetic diagram to show the possible offspring of a cross between a heterozygous red-eyed female fruit fly with a white-eyed male fruit fly

Q15 Blood Clotting and Haemophilia

• One of the genes controlling the clotting of blood in humans is also located on the X chromosome
• A rare variation of the gene, a recessive allele for haemophilia, can lead to a condition where the blood fails to clot properly
• Requires stating why a man who has haemophilia is unable to pass the condition on to his son
• Queen Victoria of Great Britain in the 19th century was a carrier of haemophilia, but did not have the condition
• State the term used to describe the genotype of a carrier
• Neither of Queen Victoria's parents carried the allele for haemophilia
• Requires suggesting how Queen Victoria could have become a carrier.
• Need to explain what is meant by a heterozygous genotype

Q16 Cat Coat Colour Genetics

• Coat colour in cats is determined by a sex-linked gene with two alleles coding for black and orange
• When black cats are mated with orange cats, the female offspring are always tortoiseshell (black and orange patches), and the male offspring are always the same colour as their mother
• Requires explaining what is meant by a sex-linked gene
• Complete is needed of the genetic diagram showing mating between a tortoiseshell female and black male
• Requires explaining why a male cat cannot have a tortoiseshell coat

Q17 Warfarin Resistance

• Resistance to the poison warfarin is now extremely common in rats
• Warfarin inhibits an enzyme in the liver, vitamin K epoxide reductase, that is necessary for the recycling of vitamin K
• This vitamin is involved in the production of substances required for blood clotting
• Rats susceptible to warfarin die of internal bleeding
• Rats that are homozygous for resistance to warfarin do not suffer from internal bleeding when their diet provides more than 70 µg of vitamin K per kg body mass per day
• Heterozygous rats are resistant to warfarin when their diet provides about 10 µg of vitamin K per kg body mass per day

Q17 Warfarin Resistance in Rats

• Using appropriate symbols, genetic diagram to show how two resistant rats can produce warfarin-susceptible offspring is needed
• Suggest why homozygous for warfarin resistance rats have a low survival rate in the wild
• Warfarin can be safely given to humans who are at risk of unwanted blood clots
• The clotting time of the blood is measured regularly and the warfarin dose is varied accordingly
• Suggest, giving a reason, the type of inhibition warfarin has on the enzyme vitamin K epoxide reductase

Q17 Warfarin effects in a gene

• The allele for warfarin resistance may have originated by a single base substitution and resulted in a modified vitamin K epoxide reductase
• Needs explanation of how a single base substitution may affect the phenotype of an organism

Q18 Meiosis II

• Fig. 4.1 shows the results of an animal cell that has undergone meiosis I
• Need to state which stage of meiosis II is shown and describe the next stage of meiosis II
• Describe what has happened before the start of meiosis to the nuclear membrane and the centrioles

Q18 Two Ways in which Meiosis Lead to Variation.

• Two ways in which meiosis can lead to variation are needed

Q19 Scallop Shell Colour

• Scallops, which are bivalve molluscs, are important commercially throughout the world
• The marine bay scallop, Agropecten irradians, has three distinct shell colours, yellow, orange and black
• The shell colour is controlled by a gene with three alleles, yellow, Sy, orange, S°, and black, Sb
• Scallops are hermaphrodite and are able to fertilise themselves to produce offspring
• Single mature adult specimens of yellow, orange and black scallops were collected and kept in separate tanks of seawater until they produced young
• The young were then scored for shell colour
• Explain needed of the results from the orange and black scallops, using the symbols given

Q19 Explanation for a Breeding Line

• Orange scallops are more valued for human consumption
• Description is needed of how a marine biologist could produce a pure-breeding line of orange scallops for commercial exploitation using the offspring from the single orange scallop

Q20 Warfarin Resistance

• Warfarin interacts with vitamin K to prevent its normal functions in the blood clotting mechanism
• Normal rats fed on warfarin suffer a fatal haemorrhage
• Resistant rats apparently do not use vitamin K in the same way and maintain normal blood clotting times even when they have eaten large amounts of warfarin
• Using the symbols R for the allele that confers warfarin resistance and r for the allele that produces no resistance, genetic diagram is needed to explain how resistant rats can produce warfarin susceptible offspring

Q20 Explaining Survival in the Wild

• Explanation as to suggest why homozygous dominant rats are unlikely to survive in the wild is necessary
• The description is needed as to how natural selection operates to maintain the proportion of resistant rats at about 50% of the total population
• Need to use an example to how a mutation that results in the substitution of a single base may affect the phenotype of an organism

Q21 Sickle Cell Anaemia in Four Generations

• Fig. 4.1 shows four generations of a family in which some members of the family suffer from sickle cell anaemia
• Using the symbols HN for the allele for normal haemoglobin and Hs for the allele for sickle cell haemoglobin, state the genotypes of the following individuals A and C
• Genetric Diagram is needed to show the probability of the parents A and B producing another child with sickle cell anaemia

Q22 Maize Plant Grains

• A maize plant produced a total of 381 grains, 216 purple and smooth, 79 purple and shrunken, 65 yellow and smooth and 21 yellow and shrunken
• Using the symbols A for purple and a for yellow and B for smooth and b for shrunken, a genetic diagram is required to explain these results
• Explain why yellow shrunken grains breed true

Q23 Completing Data

• A chi-squared test was carried out to test the significance of the differences between the observed and expected results
• Completion is needed for the missing spaces in Table 2.1
• Use the calculated values of chi-squared test and the table of probabilities to find the probability of the observed ratio of phenotypes differing significantly from the expected
• State what conclusions may be drawn from the probability found

Q23 Inheritance in Dogs

• The colour of the tips of the hair in Australian Shepherd dogs is controlled by a gene at the A locus

• There are three alleles at this locus which are:

  • As Black hair tips
  • AY Red hair tips
  • At Copper hair tips

• A cross between two dogs with copper hair tips will always produce offspring with copper hair tips

• A cross between two dogs with black hair tips may produce some offspring with red hair tips and some with copper hair tips

• State the ratio of offspring phenotypes from the following crosses:

  • ASA × AYAY
  • AsAt x AtAy
  • AYA × AyAt

Q23 Genotype

• A dog breeder wishes to know whether a dog with red hair tips is either homozygous or heterozygous for this characteristic
• State the cross needed to determine the dog's genotype
• Explain why the offspring of this cross will reveal the genotype of the dog

Q24 Cystic Fibrosis

• Outline the symptoms of cystic fibrosis (CF)
• CF is caused by a recessive mutation, b, on an autosome
• Draw a genetic diagram to show, for parents with genotypes BbXX and BbXY, the probability of having a daughter who suffers from CF
• In genetic diagram, show the genotypes of the gametes and the genotypes and phenotypes of the offspring

Q24 Explaining Mutation

• One of the many mutations for CF results in the amino acid arginine being replaced by histidine in the polypeptide encoded by the CF gene
• Explain how a mutation may cause such a change in the amino acid sequence of a polypeptide

Q24 Base Sequences

• A genetic test was performed on two individuals, D and E, to find the base sequences of a small part of the CF gene
• The different base sequences are shown diagramatically in Fig. 3.1 Individual E has CF Referencing Fig. 3.1, how the base sequence of E differs from that of D, and the effect of this difference in the polypeptide produced by the two individuals

Q25 Mouse Pigmentation

• In mice there are several alleles of the gene that controls the intensity of pigmentation of the fur

• The alleles are listed below in order of dominance with C as the most dominant is needed

  • C = full colour
  • Cch = chinchilla
  • Ch = himalayan
  • CP = platinum
  • Ca = albino

• The gene for eye colour has two alleles

• The allele for black eyes, B, is dominant, while the allele for red eyes, b, is recessive

• A mouse with full colour and black eyes was crossed with a himalayan mouse with black eyes

• One of the offspring was albino with red eyes

• Using the symbols genetic diagram to show the genotypes and phenotypes of the offspring of this cross is needed

Q26 Wild Type Feautures

• The fruit fly, Drosophila melanogaster, feeds on sugars found in damaged fruits
• A fly with normal features is called a wild type
• It has a striped body and its wings are longer than its abdomen
• There are mutant variations such as an ebony coloured body or vestigial wings
• Wild type features are coded for by dominant alleles, A for wild type body and B for wild type wings
• Explain what is meant by the terms allele and dominant
• Two wild type fruit flies were crossed
• Each had alleles A and B and carried alleles for ebony body and vestigial wings
• Draw a genetic diagram to show the possible offspring of this cross

Q26 Chi_squared

• When the two heterozygous fruit flies in (b) were crossed, 384 eggs hatched and developed into adult flies
• A chi-squared (x²) test was carried out to test the significance of the differences between observed and expected results

Q27 Pombe Disease

• Pombe disease is a rare neuromuscular disease caused by an autosomal recessive allele
• This allele prevents the production of an enzyme called acid alpha-glucosidase (AG), which breaks down glycogen in muscle cells
• Glycogen can build up in muscle cells causing damage to the cells
• State what is meant by the term antigen
• This damage leads to muscle weakness which gets worse with time
• Explain how two parents, both of whom produce normal amounts of AG, can produce a child with Pombe disease
• One form of treatment is enzyme replacement therapy where AG is given through regular injections
• Suggest how AG may be manufactured
• Name the hormone that stimulates the breakdown of glycogen in liver cells
• State under what conditions glycogen would need to be broken down in liver or muscle cells
• The MN blood group system is based on the presence of glycoproteins M and N, on the surface membrane of red blood cells, which act as antigens
• State what is meant by the term antigen

Q28 Sickle Cell Anaemia Recessive Allele

• In sickle cell anaemia the recessive allele Hbs replaces the normal allele HbA
• The frequency of Hbs is much higher in West Africa than in most parts of the world
• The frequency of Hbs corresponds with the distribution of malaria
• Explain what is meant by the term allele
• State whether the likely life expectancy is high or low in West Africa for individuals with the following genotypes In each case give a reason for your answer: HbAHDA HbAHbs HbSHbs

Q29 Tuberous Sclerosis Complex and Dominant Genetics

• Tuberous Sclerosis Complex (TSC) is a genetic condition caused by a dominant allele of the TSC gene, which leads to abnormal growth of tissue in organs such as the heart, lungs and kidneys
• Children with TSC can, with treatment, lead reasonably normal lives
• About 33% of people with TSC have at least one parent with the condition
• Explain the meaning of the terms dominant and gene
• A couple wish to start a family
• The man does not have TSC but the woman does have TSC
• Complete the genetic diagram below to show the probability of the couple's first child having TSC
• Suggest how a person may develop TSC when there is no family history of the condition

Q30 Rapid Cycling Brassicas

• A group of plants, known as Rapid Cycling Brassicas (RCBs), has been developed for use in schools and colleges for genetics experiments
• When RCB seedlings develop they can have either purple stems or non-purple stems
  • Their seed leaves can be either green or yellow-green Purple stems and green seed leaves are controlled by dominant alleles
• The genes for stem colour and seed-leaf colour are located on separate chromosomes
• Explain what is meant by a dominant allele
• Draw a genetic diagram to show the likely outcome of a cross between two RCB plants which are heterozygous for both stem colour and seed-leaf colour
• Use the symbols A / a for stem colour and B / b for seed leaf colour

Q31 Agouti Genetic Coding

• In mice, fur colour is controlled by a gene with multiple alleles
• These alleles are listed below in no particular order
  • black and tan = Cbt
  • agouti = Ca
  • yellow = CY
  • black = Cb
• Suggest explanations for the results of the following crosses between mice
  • Mice with agouti fur crossed with mice with black fur may produce all agouti offspring or some agouti and some black offspring
  • Crosses between heterozygous parents with the genotype CY Cb always produce a ratio of two yellow mice to one black mouse
  • Mice with yellow fur crossed with mice with black fur will produce one of the following outcomes

Q31 Test Crosses

• A test cross is used to determine the genotype of an organism
• Describe how to carry out a test cross to determine the genotype of a black and tan mouse

Q32 - Huntingtons Disease

• Huntington's disease (HD) is an inherited disease of the central nervous system
• The symptoms of HD usually develop in adulthood and include uncontrollable muscular movements, short-term memory loss and changes in mood
• HD is caused by a dominant allele of the huntingtin gene on chromosome 4
• Explain what is meant by the terms allele and dominant
• 32.2 Huntingtons Nucleotides
• The dominant allele of the huntingtin gene contains many repeats of a triplet sequence of nucleotides, CAG
• The age at which symptoms of HD first appear is linked with the number of CAG repeats
• A blood test to detect the dominant allele is available for people at risk of HD
• Suggest why some people at risk of HD may decide not to take the blood test

Q33 Gene Mutation in Flies

• A mutation in a gene in the fruit fly, Drosophila melanogaster, gives rise to white-eyed flies instead of the normal red-eyed flies
• The allele for red eyes (R) is dominant to the allele for white eyes (r)
• Fig 1.1 results given, and a genetic diagram showing this is requested and how the results in Table 1.1 could have been produced

Q33 Data Analysis

• The chi-squared (x2) test can be used to analyse the results in Table 1.1
• The expected ratio of red-eyed females to white-eyed males is 1:1
• Complete Table 1.2 and use this to calculate a value for chi-squared (x2)
• Use calculated value of x2 and the table of probabilities to test the significance of the difference between observed and expected results

Q34 Turners Syndrome

• Occasionally during meiosis, homologous chromosomes fail to separate at anaphase
• This is known as non disjunction
• Turner's syndrome is the most common chromosome mutation in human females
• It can occur due to non disjunction in meiosis during gametogenesis
• Some resulting gametes will be missing an X chromosome
• Some forms of Turner's syndrome occur when one of the pair of X chromosomes is not missing but has become damaged
• The damaged X chromosome may have been broken and re-formed so that part of its structure is lost
• Describe Structure K normal X chromosome and two forms of 'damaged' X chromosomes , X1 and X2
• Explain why X₁ and X2 result in different phenotypes
• Mothers with the X, form of Turner's syndrome can pass on the chromosome mutation to their daughters but not to their sons
• Complete the genetic diagram below to show how the chromosome mutation X₁ may be passed on to daughters from a mother with Turner's syndrome

Q35 Inherited Tumours

• Neurofibromatosis (NF) is a genetically inherited condition in humans where tumours grow in the nervous tissue
• One symptom, which can develop around the age of 20 years, is loss of sight due to tumours on the optic nerve

Q35 Inherited Tumours Genetic Diagram

• If one parent has NF, there is at least a 50% chance that his or her children will develop the condition, even if the other parent is unaffected
• Complete the genetic diagram below to show how NF may be transmitted from parent to child
• Suggest how a person may develop NF when there is no family history of the condition
• Suggest how a tumour on the optic nerve could prevent the transmission of nerve impulses to the brain

Q36 PKU Genetic Mutation

• Phenylketonuria (PKU) is a genetic disease which results in a raised concentration of the amino acid phenylalanine in the blood
• If left untreated in a newborn baby, it can lead to brain damage
• For this reason, babies may be tested for PKU soon after birth
• Usually, excess phenylalanine is converted to the amino acid tyrosine by the enzyme phenylalanine hydroxylase (PAH)
• PKU can be the result of a recessive mutation of the gene coding for PAH
• Explain what is meant by a recessive mutation
• Using appropriate symbols, genetic diagram below to show how two parents who do not have PKU can have children with, or without, PKU is needed
• PKU can be caused when a short length of the RNA produced during transcription of the gene coding for PAH is lost
• Suggest what effect this would have on the protein that is subsequently produced

Defining Alleles and Genes

• Distinguish between the terms gene and allele
• Given pedigree diagrams for information, genetic analysis and completion skills are requested

Section B Questions

• Outline the behaviour of chromosomes during meiosis
• Describe the ways by which gene mutations can occur
• Explain how changes in the nucleotide sequence of DNA may affect the amino acid sequence in a protein
• Explain how the allele for haemophilia may be passed from a man to his grandchildren Describe the first division of meiosis (meiosis I) in animal cells
• Discuss the link between the frequency of sickle cell anaemia and the number of cases of malaria