Inheritance

Question 1

Who was Mendel and what What did Mendel do?

Answer 1

Mendel-
• Discovered basic principles of inheritance
• Defined laws to explain how genes pass on from one generation to another
o Law of independent assortment
o Law of segregation
• Set the theoretical basis of genetics and modern inheritance before we knew about DNA
• Mendel was a monk who bred pea plants to see how inheritance works, tracking inheritance of discrete traits such as colour through cross-pollination experiments. His success was recognised 50 years after his death
o Controlled crosses with pure-breeding varieties observing simple discrete phenotypes
o Many replicates and test crosses were important for the success of his experiments

Question 2

What is the law of independent assortment?

Answer 2

alleles of one gene sort into gametes independently of the alleles of another gene (not always true)

Question 3

What is the law of segregation?

Answer 3

the alleles of a given locus segregate into separate gametes. Each gamete only gets one allele of each gene

Question 4

What phenotypic ratio does a Dihybrid cross (2 genes) using heterozygous population with dominant/recessive traits independently assorting give?

Answer 4

9:3:3:1

Question 5

How do you do a dihybrid cross punnet square?

Answer 5

• For dihybrid cross punnet square-
o First find potential gametes that one parent could produce and cross that with potential gametes that other parent could produce
o Probability of each phenotypic class can be calculated based on the frequency of gametes produced by each parent

Question 6

What phenotypic ratio does a Monohybrid cross using heterozygous population with dominant/recessive traits give?

Answer 6

3:1

Question 7

What are genes?

Answer 7

physical units of heredity (defined DNA sequences)

Question 8

What are chromosomes?

Answer 8

long molecules of double-stranded DNA and protein, which contain genes

Question 9

What is a phenotype?

Answer 9

the observable traits of an organism

Question 10

What is a genotype?

Answer 10

the genetic constitution of an organism

Question 11

What is a wild type?

Answer 11

the most common variant in the wild

Question 12

What are alleles?

Answer 12

alternative (variant) forms of a gene

Question 13

What is a homozygote?

Answer 13

Contains two copies of the same allele

Question 14

What is a heterozygote?

Answer 14

Contains two different alleles

Question 15

What is a dominant trait?

Answer 15

Trait will be expressed in heterozygote

Question 16

What is a recessive trait?

Answer 16

Trait will be masked by dominant allele

Question 17

Why do we need statistics in genetics?

Answer 17

• Need statistics as we only have finite number of samples in each experiment- makes conclusions more certain
• Statistics give us a probability value how likely it is that our hypothesis about inheritance is correct
o If probability value obtained is bigger than 0.05, can be often confident that we are correct

Question 18

What does chi-square hypothesis testing test?

Answer 18

• Tests wow well the observed number of offspring (O) fits with the expected (E) number of offspring

Question 19

What is the formula for chi square hypothesis testing?

Answer 19

χ^2=

Σ((O-E)^2/E))

Question 20

How do you perform chi square hypothesis testing?

Answer 20

1. Form a hypothesis about the expected offspring based on predicted phenotypic ratios (Null hypothesis/H0)
2. Calculate expected values based on total number of observations
    Total multiplied by predicted ratio
3. Calculate the chi-square values for each class
    Each different phenotype- one discrete category/class
    Add the values together to get final chi square value
4. Determine degrees of freedom
    Calculated as the number of phenotypic categories (or the number of alleles) (n) minus 1
   • (n-1)
5. Determine the probability (p) associated with the chi-square value
    Use table of chi-square values

Question 21

Why do mutant phenotypes arise?

Answer 21

Mutant phenotypes are due to mutations in the DNA sequence of genes

Question 22

What can variation in amino acid sequences result in?

Answer 22

o Variation in amino acid sequences can result in related proteins with some differences in function

Question 23

What can variation in gene regulation result in?

Answer 23

o Variation in gene regulation can change the amounts of gene product being made and/or change when and where the gene is expressed

Question 24

What can variation in intron and exon splicing in mRNA result in?

Answer 24

o Variation in intron and exon splicing of mRNA can result in proteins with different functional domains present or absent

Question 25

What can novel genes and functions result in?

Answer 25

o Novel genes and functions, although rare, can have a significant impact

Question 26

What are the seven phenotypes Mendel followed in peas and what are their dominant/recessive versions?

Answer 26

o Flower colour
 Purple- dominant
 White-recessive

o Flower position
 Axial- dominant
 Terminal- recessive

o Seed colour
 Yellow- dominant
 Green- recessive

o Seed shape
 Round-dominant
 Wrinkled- recessive

o Pod shape
 Inflated- dominant
 Constricted- recessive

o Pod color
 Green-dominant
 Yellow- Recessive

o Stem length
 Tall- dominant
 Dwarf- recessive

Question 27

What gene is flower colour in peas controlled by and how?

Answer 27

 Controlled by basic-helix-loop-helix (bHLH) transcription factor
• bHLH switches on expression of genes involving in making anthocyanin (purple) pigments
o bHLH binds to promoter of gene which leads to transcription of protein that makes anthocyanin pigments
• When it isl mutant, flower is white
o When there is G->A mutation in bHLH gene, bHLH transcription factor is not produced which means that can no longer bind to promoter of gene and protein that makes antocyanin pigment is not produced, turning the flower white

Question 28

What gene is seed colour in peas controlled by?

Answer 28

 Controlled by magnesium dechelatase gene (stay-green gene):
• Positive regulator of the chlorophyll degrading pathway
• When it is mutant, seed colour is green

Question 29

What gene is seed shape in peas controlled by and how

Answer 29

 Controlled by starch-branching enzyme 1 (sbe I)
• Converts amylose to amylopectin, the branched form of starch (starch is a polymer of glucose subunits, some of which are linear and some are branched)
• When it is mutant, peas are wrinkled
o In round peas, starch branching enzyme links all linear glucose molecules together to produce starch, which is a rigid structure making the peas appear round
o The starch branching enzyme is wrinkled in peas, leading to reduced concentrations of amylopectin, the branched form of starch as glucose polymers not joined together
 Higher sugar content means less water in peas making it wrinkled

Question 30

What gene is stem length in peas controlled by?

Answer 30

 Controlled by gibberellin 3 beta-hydroxylase:
• Gibberellin is a growth hormone that stimulates cell elongation and cases plants to grow taller
• When it is mutant, plants are dwarves

Question 31

Are dominance relationships between multiple alleles relative or not?

Answer 31

• Dominance relationships between multiple alleles are relative

Question 32

What are dominance relationships dependant on?

Answer 32

Context and what you measure

Question 33

What is co-dominance?

Answer 33

a heterozygote expresses the phenotype of both alleles simultaneously

Question 34

What is an example of co-dominance?

Answer 34

 EG. ABO blood antigens
• IA and IB allele produce A and B antigens and these alleles are co-dominant with each other, leading to an AB phenotype
• Dominant to i allele (basis of O blood) that produces nothing

Question 35

What is incomplete dominance?

Answer 35

A heterozygote is intermediate between the two homozygous phenotypes

Question 36

What is an example of incomplete dominance?

Answer 36

cross between a red lower and white flower gives pink flower

Question 37

What is a loss of function mutation and are they usually dominant or recessive?

Answer 37

 Decrease or complete loss of functional gene product
• Partial loss of gene function- leaky or hypomorphic mutation
• Complete loss of gene function- null mutation
 These mutations are usually recessive
-Include haplo-sufficient and haplo-insufficient mutations

Question 38

Describe haplo-sufficient mutations. Are they usually recessive or dominant?

Answer 38

 Haplo-sufficient- one wild type allele provides enough normal gene product to produce a wild-type phenotype
• The mutation is recessive

Question 39

What is an example of haplo-sufficient mutations?

Answer 39

• Example- albinism
o Albinism results from loss of melanin pigmentation in skin cells
o Several genes control the synthesis of melanin in melanocytes
 Tyrosinase gene takes tyrosine (unpigmented) and converts it into melanin (brown pigmentation)
 Tyrosinase loss of function mutants are recessive
 Sufficient enzyme produced in heterozygotes for normal pigmentation
 Wild-type allele is haplo-sufficient

Question 40

What is a haplo-insufficient mutation and are they usually dominant or recessive?

Answer 40

 Haplo-insufficient- a single wild-type allele in a heterozygote cannot provide the amount of gene product needed
• The mutation is dominant

Question 41

What is a gain of function mutation and are they usually dominant or recessive?

Answer 41

 Increase in functional gene product or new cellular function
 These mutations are usually dominant

Question 42

What is an example of a gain of function mutation?

Answer 42

 EG- drosophila malenogaster
• In drosophila melanogaster, the Antp gene is a homeotic gene (developmental regulator) that promotes leg growth
• Antennapedia mutants arise from the mis-expression of the Antp gene causing legs to grow where antennae should be
• Mutation is dominant because the gain-off-function cannot be compensated by the wild-type allele and heterozygotes show the phenotype

Question 43

Do genes only have 2 different alleles within a population?

Answer 43

• While diploid individuals can only contain 2 alleles per locus, genes can have many different alleles within a population

Question 44

What is an allelic series and how is it determined?

Answer 44

• Alleles form an order of dominance or an allelic series, according to phenotypes expressed in the heterozygotes
o Have to figure out relative dominance between multiple alleles

Question 45

Describe the allelic series of the agouti gene in mice looking at the a^y, a^w-j and a alleles

Answer 45

o The agouti in mice has more than 100 different alleles, including the black a allele, the yellow A^Y allele and the agouti A^w-J allele, which forms an allelic series of A^y>A^w-j>a

Question 46

Describe how the agouti gene works

Answer 46

the agouti locus produces a molecule that regulates the synthesis of black pigment eumelanin
 Different alleles of the agouti locus modify this pattern of bands on a hair shaft in various ways, with pheomelanin appearing when eumelanin production is blocked

Question 47

Describe the agouti gene allelic sequence in dogs looking at the a^y, a^w, a^t and a alleles

Answer 47

 In dogs, the ay allele blocks synthesis of eumelanin so is dominant to all other alleles
 Allele a^y>a^w>a^t>a
 a lacks the ability to control distribution eumelanin, giving a completely black coat

Question 48

Describe the allelic sequence of the C gene in rabbits looking at the C, c^ch, c^h and c alleles, what each of these alleles represent and how these mutations occured

Answer 48

o The C gene contains multiple alleles including the C allele (resulting in black rabbits), the c^ch allele (resulting in chinchilla grey rabbits), the c^h allele (resulting in himalayan rabbits) and the c allele, resulting in white rabbits
o The allelic series is C>c^ch>c^h>c
o The c,c^ch and c^h recessive alleles result in a decrease or complete loss of functional gene product
 Chinchilla is partial loss of gene function (leaky or hypomorphic mutation)
 White is complete loss of gene function (null mutation)
 Himalayan is conditional mutation (mutant phenotype is temperature sensitive)
• Enzyme active at low temperatures (black ears, nose…)
• Enzyme inactive at high temperatures (white cores)

Question 49

What are conditional mutants?

Answer 49

• Conditional mutants- mutation causes a phenotype only under certain environmental conditions (e.g. temperature, chemical exposure, resource availability)

Question 50

What 2 different conditions are there in conditional mutants?

Answer 50

o Restrictive condition- mutant phenotype (restricts growth of individual)
o Permissive condition- wild-type phenotype (allow growth of individual/normal phenotype)

Question 51

What is incomplete penetrance?

Answer 51

• Incomplete penetrance- not every individual with the mutant genotype displays a mutant phenotype

Question 52

What is penetrance?

Answer 52

o Penetrance- the proportion of individuals of a specific genotype that exhibits the corresponding phenotype

Question 53

What is an example of incomplete penetrance?

Answer 53

o e.g. polydactyly
 Single dominant gene, causing growth of extra fingers and toes
 Incomplete penetrance- at least 1 in 4 people with the mutation have 5 digits (penetrance=0.75: ¼ of people have normal phenotype and ¾ of people have mutant phenotype)

Question 54

What are lethal alleles?

Answer 54

alleles that cause the death of the organism that carries them

Question 55

What is an example of a lethal allele?

Answer 55

o Example: the agouti AY allele in mice
 In mice, A alleles produce wild-type (agouti): dark hair with yellow band
 The AY allele in mice is a gain of function mutation resulting in ubiquitous overexpression of the agouti protein (mutants produce solid yellow hair)
 Homozygous mutants are embryonic lethal
• Not possible to generate a pure-breeding yellow line

Question 56

What is the mendelian ratio for dominant lethal alleles?

Answer 56

 Dominant lethal alleles
• Homozygous dominant mutant will die
• Offspring ratio= 2:1

Question 57

What is the mendelian ratio for recessive lethal alleles?

Answer 57

 Recessive lethal alleles
• Homozygous recessive mutant will die
• Offspring ratio: 1 (all same dominant phenotype)

Question 58

What is a pleitropic gene?

Answer 58

• Pleitropic genes- a single gene that affects more than one phenotype or process

Question 59

What is an example of a pleitropic gene and why is it lethal?

Answer 59

o Example- the agouti AY allele affects both coat colour (yellow dominant), weight (obese dominant), tumor susceptibility, hyperinsulemia (leading to embryonic lethality)
 Too much agouti protein results in increased antagonism of melanocortin receptors

Question 60

How could mutants with the same phenotype occur?

Answer 60

• Mutants with the same phenotype could be alleles of the same gene, or mutations in two different genes

Question 61

Describe the 5 genes that contribute to coat colour

Answer 61

 A gene (agouti)- determines distribution of pigment along the hair
 B gene- determines the colour of pigment
 C gene- permits colour expression
 D gene- controls the intensity of pigment
 S gene- controls distribution throughout the body (spotting)

Question 62

What is the complementation test for and how does it work?

Answer 62

• The complementation test- a functional test between recessive mutants with the same phenotype

Process:
o Two homozygous recessive mutants with the same phenotype are mated
o F1 offspring are analysed
o If the F1 is a wild-type, the two mutations complement each other and represent two different genes
o If the F1 is a mutant, the two mutations fail to complement and represent two different alleles of the same gene

Question 63

How can we determine if gene interactions are occuring?

Answer 63

• Genes rarely act in isolation
• Can use genotypic and phenotypic ratios of some crosses to determine how many and what type of gene interactions are occurring
o If deviation from expected ratios, means some kind of gene interaction is occurring

Question 64

What are 5 different types of gene interactions?

Answer 64

• No interaction
• Complementary gene interaction
• Duplicate gene interaction
• Dominant gene interaction
• Epistasis
• —-Recessive epistasis
• —-Dominant epistasis
• —-Dominant suppression epistasis

Question 65

What is the mendelian ratio for no gene interaction and what does no gene interaction mean?

Answer 65

 Two genes, no interaction

 Get a 9:3:3:1 ratio

Question 66

What is complementary gene interaction and what is its mendelian ratio?

Answer 66

 Two genes act sequentially to produce a phenotype. Both are required
 Get a 9:7 ratio

Question 67

What is duplicate gene interaction and what is its mendelian ratio?

Answer 67

 Two genes perform the same function (redundancy). Either are required
 Get a 15:1 ratio

Question 68

What is dominant gene interaction and what is its mendelian ratio?

Answer 68

 Two genes with the same phenotype interact additively (causes enhanced/additive phenotype)
 Get a 9:6:1 ratio

Question 69

What is epistasis?

Answer 69

 One gene stops/masks the phenotype of another gene

Question 70

What is recessive epistasis and what is its mendelian ratio?

Answer 70

• Recessive epistasis- homozygous recessive alleles for one gene masks the phenotypic expression of alleles at a second gene. Most common epistasis version.
o Get a 9:3:4 ratio

Question 71

What is dominant epistasis and what is its mendelian ratio?

Answer 71

• Dominant epistasis- dominant allele of one gene masks the phenotypic expression of another gene
o Get a 12:3:1 ratio

Question 72

What is dominant suppression epistasis and what is its mendelian ratio?

Answer 72

• Dominant suppression epistasis- dominant allele of one gene suppress the expression of the dominant allele of another gene
o Get a 13:3 ratio

Question 73

Describe when chromosomes were first visualised

Answer 73

• Chromosomes visualised as early as 1842

Question 74

Describe when the process of division was first described

Answer 74

• Process of division described later (1873-82)• Process of division described later (1873-82)

Question 75

What are the 2 types of cell division, where do they each take place and what is the chromosome number relative to parent cells in their daughter cells?

Answer 75

o Mitosis- Somatic cells: Chromosomes replicate and divide, and chromosome number is maintained in daughter cells
o Meiosis- Germline cells: Chromosomes replicate and undergo 2 rounds of division: chromosome number is halved in daughter cells

Question 76

What is a karyotype?

Answer 76

• Complete set of chromosomes is called a karyotype

Question 77

Is chromosome number the same in every species?

Answer 77

No

Question 78

How many chromosomes do humans have?

Answer 78

o Complete set of human chromosomes is 23 pairs (46 chromosomes)

Question 79

What is a homologous chromosome pair?

Answer 79

• A homologous chromosome pair has similar DNA sequence and encodes the same genes

Question 80

What is the chromosome theory of inheritance? (Sutton and Boveri 1902)

Answer 80

Chromosome theory of inheritance states that individual genes are found at specific locations on particular chromosomes, and that the behavior of chromosomes during meiosis can explain why genes are inherited according to Mendel’s laws

Question 81

Describe what experiment proved the chromosome theory of inheritance

Answer 81

• At the time it was proposed, the chromosome theory of inheritance lacked experimental proof and was wildly controversial
o Morgan and drosophila melanogaster (1910)
 Experimental evidence came from one of the first identified mutants in Drosophila melanogaster: a male with white eyes which is unusual as the wild type usually have red-eye colour
 Morgan crossed his white type male to his wild type female, and got all wild type offspring (F1 individuals)
 Morgan then crossed all his F1 individuals together but found that none of the females were white eyed, but half the males had red eyes and the other half had white eyes (not the 3:1 ratio expected)

Question 82

What are observations that support the chromosome theory of inheritance?

Answer 82

o This is because chromosomes come in homologous pairs, and one member of the pair comes from the mother and the other from the father
o The members of a homologous pair separate in meiosis, so each sperm or egg receives one- This process matches the segregation of alleles into gametes in Mendel’s law of segregation
o Different chromosome pairs sort into gametes independently of one another in meiosis, like as predicted for genes in Mendel’s law of independent assortment

Question 83

What are ABC transporters?

Answer 83

o ABC transporters-ATP-Binding cassette transporters which are transmembrane proteins that use ATP to transport molecules across membranes

Question 84

Describe what role the white gene in drosophila has on drosophila eye colour

Answer 84

• The white gene is an ABC transporter required for eye pigment production
• White gene occurs upstream of many pigmentation genes and delivers pigment precursors guanine and tryptophan to the eye to make the brick red pigment
o Trypotophan, aided or regulated by many genes, eventually makes zanthommatin brown pigment
o Guanine, aided or regulated by many genes, eventually makes drosopterin, orange pigment
• Xw mutation blocks the transport of pigment precursors guanine and tryptophan, resulting in white eyes

Question 85

When were sex chromosomes first discovered?

Answer 85

• Nettie Stevens (1905) used the mealworm beetle to show that:
o Male gametes had 10 large chromosomes, or 9 large chromosomes and 1 small chromosome
o Female gametes all had 10 large chromosomes
• Observed sex-based differences in chromosomes from a range of insects

Question 86

Do all organisms have sex chromosomes?

Answer 86

• In many organisms, sex is determined by the presence of sex chromosomes but some organisms do not have sex chromosomes

Question 87

What is the heterogametic sex?

Answer 87

• Heterogametic sex- the sex with different sex chromosomes

Question 88

What is the homogametic sex?

Answer 88

• Homogametic sex- the sex with homologous sex chromosomes

Question 89

What is a hemizygote?

Answer 89

• Hemizygote- Only one copy of an allele is present at a locus instead of two. The phenotype is present regardless of dominance

Question 90

What are the two human sex chromosomes?

Answer 90

X and Y

Question 91

Are human males heterogametic or homogametic?

Answer 91

Heterogametic (XY)

Question 92

Are human females heterogametic or homogametic?

Answer 92

Homogametic (XX)

Question 93

Describe the origin of human sex chromosomes

Answer 93

o Sex chromosomes in humans were originally derived from a pair of homologous autosomes (non-sex chromosomes)
1. The Y chromosome acquired a sex determining locus
• Accumulated genes with functions in sex and male fertility
2. Differentiation of X and Y specific regions, with small regions of homology retained in pseudo-autosomal regions (which help X and Y chromosomes to pair up during cell division)
3. Y chromosome lost genes and accumulated mutations
4. Dosage compensation
5. Final heteromorphic chromosomes differ greatly in size and morphology
-Over evolutionary time, they have changed in size and morphology

Question 94

Describe how many megabases and genes the X chromosome has and how conserved this gene is in placental mammals

Answer 94

o The X chromosome
 165 Megabases, about 1000 genes
 Highly conserved in placental mammals

Question 95

Describe how many megabases and genes the X chromosome has, describe its composition and role as well as its evolution

Answer 95

o The Y chromosome
 59 Megabases, about 200 genes
 Specialised male fertility genes
 Many residual and non-functional sequences
 Many human sex-linked traits predominantly affect males
 Y chromosome has changed due to gene loss over time
 Sex determining region on the Y chromosome

Question 96

What is a pseudoautosomal region?

Answer 96

o Pseudoautosomal region- regions of chromosomes that have maintained homology

Question 97

What are genes on the X chromosomes called?

Answer 97

X-linked genes

Question 98

What are genes on the Y chromosome called?

Answer 98

Y-linked genes

Question 99

Describe the offspring ratio that occurs when there is a Parental cross of homozygous wild-type female with hemizygous mutant male involving a sex-linked trait

Answer 99

• Parental cross of homozygous wild-type female with hemizygous mutant male results in a 2:2:1: ratio when trait is sex linked
o 2 female wild type: 2 male wild-type: 1 mutant male

Question 100

Describe the offspring ratio that occurs when there is a parental cross of a heterozygous wild-type female with hemizygous mutant male involving a sex-linked trait

Answer 100

• When trait is sex-linked, parental cross of a heterozygous wild-type female with hemizygous mutant male results in a 1:1:1:1 ratio when trait is sex-linked
o 1 female wild type:1 female mutant:1 male wild-type: 1 male mutant

Question 101

What is criss-cross inheritance?

Answer 101

• Criss-cross inheritance- the trait goes from mother to son, mirroring the inheritance of the X chromosome
o Mothers will only pass on X chromosomes to their sons, and fathers will only pass on X chromosomes to their daughters

Question 102

What can be inferred of the mother’s genotype if the son’s phenotype is provided

Answer 102

o Mothers that are carriers of the trait are assumed based on the phenotype of sons
 Unaffected mothers with affected sons must be heterozygotes
 Mothers who are not affected when their sons are is a way of guessing that it is a sex-linked trait

Question 103

Describe what population is affected by Y-linked inheritance

Answer 103

o Trait occurs in males only
o Occurs in all sons of the affected males
o Daughters of affected males are normal and do not have affected offspring

Question 104

Describe the consequences of X-linked dominance inheritance in a family tree
(What genotype will result in the trait being phenotypically present in males/females, what will happen phenotypically if an affected heterozygous female is mated to a normal male, and what will happen phenotypically when affected hemizygous males will mate)

Answer 104

 Trait is present in males hemizygous for the allele
 Trait is present in females homozygous or heterozygous for the allele
 Each individual who has the disease has at least one affected parent
• Affected heterozygous females mated to normal males transmit the defect to ½ of their sons and ½ of their daughters
• Affected hemizygous males transmit to all their daughters
• Every affected has at least one affected parent, except in the case of de-novo mutations

Question 105

Describe the consequences of X-linked recessive inheritance in a family tree
(What genotype will result in the trait being phenotypically present in males/females, what will happen phenotypically if a heterozygous female is mated to a normal male, what will happen phenotypically when affected hemizygous males will mate and what will happen if affected females mate with normal males)

Answer 105

 Trait is present in males hemizygous for the allele
 Trait is present in females homozygous for the allele
 The defect or disease may skip generations
• Normal parents with a female carrier will give no affected females and ½ affected males
• Affected males mated to normal females will have no affected offspring, but all daughters are carriers
• Affected females mated to normal males will have all sons affected and no affected daughter, but all daughters are carriers

Question 106

Describe the inheritance pattern of autosomal recessive inheritance (if one or all parents have the disorder, what is the phenotype of the children, and is it affected by sex)

Answer 106

o Autosomal recessive inheritance
 Individuals who have the disease are often born to parents wo do not
 If only one parent has the disorder the risk that a child will have it depends on the genotype of the other parent
 If both parents have the disorder, all children will have it
 The sex ratio of affected offspring is expected to be equal
 The disease is not usually seen in each generation but if an affected child is produced by unaffected parents, the risk to subsequent children is ¼
 If the disease is rare in the population, unaffected parents of affected children are likely to be related to one another

Question 107

Describe the inheritance pattern of autosomal recessive inheritance (if one, all or none of the parents have the disorder, what is the phenotype of the children, and is it affected by sex)

Answer 107

 Each individual who has the disease has at least one affected parent
 Males and females are affected in equal numbers
 Either sex can transmit the disease allele
 In crosses where one parent is affected and the other is not, approximately half the offspring have the disease
 Two unaffected parents will not have any children with the disease
 Two affected parents may produce unaffected children

Question 108

Describe genetic allelic notation for Drosophila recessive, dominant or sex-linked traits

Answer 108

o	Instead of lower case upper case allelic notations, wild-type alleles are indicated by a + superscript. 
	For a recessive trait with allele e
•	Wild type allele: e+
	For a dominant trait with allele B
•	Wild type allele: B+
	For a sex-linked trait with allele w:
•	Wild type allele: Xw+
o	Dominant mutations are given a capital letter and recessive mutations are lower case

Question 109

Describe the chromosome composition and appearance in Drosophila melanogaster

Answer 109

o Drosophila melanogaster have 4 chromosomes
o 1 X chromosome and 3 autosomes
o Each chromosome has a left and right arm at either side of the centromere except for chromosome 4

Question 110

Describe sex determination in Drosophila

Answer 110

• Sex determination in Drosophila depends on the number of X chromosomes, not on the presence of a Y chromosome: two X chromosome is a female and one X chromosome is a male
o XX or XXY= female
o XY or XO= male

Question 111

What are reciprocal crosses and what is their purpose?

Answer 111

• Used to determine sex-linkage: two crosses are performed, where the genotypes of the male and female parents are swapped
• If F1 offspring ratios differ, it indicates that this trait is sex-linked

Question 112

What are pedigrees and what are they useful for?

Answer 112

• Pedigrees, or family trees, are a way of tracing the inheritance of traits
• They are useful to understand the mode of inheritance of a trait when offspring numbers are low, but family records are available

Question 113

Describe the symbol used in pedigrees for:

• Males
• Females
• Unaffected
• Affected
• Heterozygous
• Deceased
• Unspecified sex
• Generation
• Parents
• Parents related by blood
• Adoption
• Siblings
• Identical twins
• Fraternal twins
• Generations
• Individuals in a generation

Answer 113

• Males: square
• Females: Circle
• Unaffected: Empty square/circle
• Affected: Filled square/circle
• Heterozygous: Dot inside square/Circle
• Deceased: Diagonal line (from bottom left to top right inside shape)
• Unspecified sex: Diamond
• Generation: Vertical line
• Parents: Horizontal line
• Parents related by blood: 2 horizontal lines
• Adoption: Dotted vertical line
• Siblings: Horizontal line joining vertical lines
• Identical twins: Two lines joined by horizontal line
• Fraternal twins: Two lines
• Generations: Indicated by roman numberals
• Individuals in a generation: Indicated by arabic numerals

Timestamp: 3:40 on the 13/08/2019

Question 114

What is autosomal dominant?

Answer 114

one mutant allele is sufficient for trait or disease

Question 115

What is autosomal recessive?

Answer 115

two mutant alleles result in trait or disease

Question 116

What is X-linked

Answer 116

hemizygous males express the trait, regardless of dominance

Question 117

Describe the pattern of inheritance of many genetic traits and diseases

Answer 117

• Thousands of human genetic traits and diseases are caused by mutations of single genes which follow mendelian patterns of inheritance
• Can occur on autosomes or sex chromosomes

Question 118

Why is genetic testing important and what can be done in genetic testing?

Answer 118

• Many deleterious alleles causing genetic diseases are recessive (autosomal or X-linked)
o Detection of carriers is important as carrierxcarrier matings will give affected offspring in autosomal genes at ¼ frequency
• Can do molecular test where alleles of individuals are examined and detect whether the offspring has inherited 2 mutant alleles
o Can also result in employment of personalised medicine where treatment is targeted to a person’s specific genomes and susceptibility

Question 119

Describe commercial genetic testing

Answer 119

• Commercial genetic testing can report one’s traits and genetic characteristic but results should always be interpreted with a medical background as well, not just a genetic background and commercial genetic testing has many limitations.

Question 120

What is sexual dimorphism and examples of these

Answer 120

• Many species exhibit sexual dimorphism- physical differences between males and females. For example:
o Colour dimorphism
o Size dimorphism

Question 121

What are two different mechanisms for sex determination?

Answer 121

• There are lots of different mechanisms for sex determination-
o Both genetic and environmental sex determination mechanisms exist

Question 122

What are monoecious plants?Give an example

Answer 122

• Monoecious plants- male and female flowers on the same plant such as zucchini

Question 123

What are hermaphrodites?

Answer 123

o Hermaphrodites- contain both male and female sex organs

Question 124

What percentage of plants are hermaphrodites?

Answer 124

 94% of plants have both male and female organs, often within the same flower

Question 125

What percentage of animals are hermaphrodites?

Answer 125

 About 5% of animals (some worms, snails and fish (such as clownfish)) are hermaphrodites

Question 126

What are dioecious plants, the percentage of dioecious plants and examples of these?

Answer 126

• Dioecious plants- male and female flowers on different plants
o Only 6% of plants have split into different sexes, including papaya and asparagus

Question 127

What is genetic sex determination and how does it work?

Answer 127

genetic elements specify whether individuals are female or male
o Individuals release some genetic signal during embryonic development to tell to develop as male or female

Question 128

What are 3 different types of genetic sex determination and in what animals are they present?

Answer 128

 Heteromorphic sex chromosomes- the presence of specific sex chromosomes that are different and visually distinct from each other, and distinct from autosomes
• Heterogametic sex- the sex with different sex chromosomes
• Homogametic sex- the sex with homologous sex chromosomes
• For example, mammals, birds, some reptiles and fish, many invertebrates

 Sex-determining genes on homomorphic chromosomes
• Sex-determining/mating type genes are located on autosomes
• Species do not have sex chromosomes
• Amphibians, some reptiles and fish, some invertebrates
o E.g. swordtails: a mating-type gene with 2 alleles determines sex. Females are homozygotes and males are heterozygotes

 Chromosome ploidy:
• Males develop from unfertilised eggs and are haploid (n)
• Females develop from fertilized eggs and are diploid (2n)
• Invertebrates (all bees, wasps, ants, most mites and ticks)

Question 129

What is environmental sex determination?

Answer 129

• Environmental sex determination- external stimuli control sex determination
o Favoured when specific environments are more beneficial to one sex

Question 130

Describe the order in which sex determination evolved in vertebrates (animal and chromosome type order, not evolution of actual chromosomes)

Answer 130

1. Reptiles and birds:
   o Birds: ZW, Reptiles: ZW, XY and environmental
   o Sex chromosomes have no homology to mammalian XY (come about on different chromosomes present in these organisms).
2. Mammals
   o XY(or variations)
   o Monotremes: earliest offshoots of the mammalian lineage

Question 131

What are the impacts of climate change on temperature sex-determination?

Answer 131

• Sex determination is quite robust-genetic sex determination that can transition in environmental mechanism and vice-versa

Question 132

Describe sex determination in australian bearded dragons

Answer 132

• Australian bearded dragons use both sex chromosomes and temperature to determine sex
o Normal temperature:
 Heteromorphic sex chromosomes and genetic sex determination
• ZW females and ZZ males
o High temperatures higher than 32
 Male dragons with ZZ sex chromosomes undergo sex reversal and develop as female
• W chromosome eliminated from population
 Must be advantages to having more females as females are favoured in high temperature zones
o Transition to environmental sex determination

Question 133

What are different types of chromosomal genetic systems?

Answer 133

• XY systems
• XO systems
• ZW systems
• Haplo-diploidy

Question 134

Describe the genetic XY system:

Male vs female, animals involved, master-sex determining locus

Answer 134

 Female: XX
• The absence of SRY allows expression of genes needed for ovary differentiation (the default pathway)
 Male: XY
• In mammals, the presence of the Y chromosome determines if an offspring develops as a male
• Male sex depends on a master sex-determining locus, the SRY (sex determining region Y) gene
• SRY encodes a protein, the testis-determining factor (TDF) which leads to testis differentiation and male sexual development

Question 135

Describe sex determination of monotremes

Answer 135

 Monotremes have 10 sex chromosomes
• Females have 10 X chromosomes, males have 5X and 5Y chromosomes
• X1 chromosome has homology to other mammal X chromosomes

Question 136

Describe the XO genetic system (Males vs female, animals involved)

Answer 136

 Female: XX, XXY
 Male: XO, XY
 The number of X chromosomes determines sex in Drosophila and many other invertebrates
• More than one X chromosome- female
• One X chromosome- male
 In many nematodes and other insects, there is no Y chromosome- XX are female and XO are male e.g. C elegans

Question 137

What is the master-sex determining locus in drosophila and how does it work?

Answer 137

 The drosophila chromosome is not involved in sex determination but contains genes required for male fertility. An XO is male but sterile.
• Sex-lethal (Sxl) is the master sex-determining locus in Drosophila
o XX embryo: High sex-lethal expression, which triggers production of the female isoform of the gene doublesex (dsx) via alternate splicing, leading to female development and results in no hypertranscription of X
o XY or XO embryo: low Sxl expression which leads to production of the male isoform of dsx and results in hypertranscription of X

Question 138

What is the sec-determining locus in C.elegans and how does it work?

Answer 138

• XX means that master sex-determining locus xol-1 is off, which makes a hermaphrodite
• XO means that the master sex-determining locus xol-1 is on, which makes a male.

Question 139

Describe the ZW genetic system (Males vs females, animals involved, description of chromosomes)

Answer 139

 Female: ZW
 Male: ZZ
 All birds, some reptiles, some insects and fish
 Males are the homogametic sex (ZZ) while females are the heterogametic sex (ZW)
• Z chromosome: large, gene rich
• W chromosome: Small, few genes
 ZW heteromorphic chromosomes are structurally similar to XY (large vs small) but have completely different gene content
• Dose-dependent Z (need multiple copies of Z to become a male)

Question 140

What is the master sex-determining gene in birds?

Answer 140

• Master sex-determining gene: dmrt1

Question 141

Describe the haplo-diploidy genetic system (males vs females)

Answer 141

 Female: Diploid

 Male: Haploid

Question 142

Describe honey bee sex determination (chromosome number, sex determiner gene)

Answer 142

Haplo-diploidy
 E.g. honey bees
• Females have 32 chromosomes (16 pairs) whilst males have 16 unpaired chromosomes
• Males can only have daughters (if produce diploid malformed males are killed by the colony at development)
• Sons do not have fathers
• Sex is determined by the complementary sex determiner (csd) gene
o Males are haploid and hemizygous for csd
o Females must be heterozygous at the csd locus to develop normally
o Homozygous diploid eggs develop into inviable males
o There are hundreds of different csd alleles
o Honey bee queens mate with over 20 different males to ensure that they have high diversity of alleles at this gene
 Will have sperm stored in their ovaries to make sure they can fertilise eggs with lots of csd alleles to make sure they have lots of female heterozygous offspring

Question 143

Describe 3 examples of environmental sex determination systems

Answer 143

• Environmental systems
o Temperature of egg incubation in reptiles (such as turtles)
 Female: Warmer temperatures
 Male: Cooler temperatures
o Photoperiod in marine amphipods
o Social factors in many coral reef-dwelling fish

Question 144

What are sex determination abnormalities that can occur in species where sex is cell autonomous?

Answer 144

o Gynandromorphs- embryos develop as part male and part female, often leading to spectular phenotypes
 Chimeras- fusing of two embryos in early development
 Polyspermy- multiple sperm fertilise egg, different lineages develop
 Errors in mitotic division early in development (sex chromosome loss)

Question 145

What does cell autonomous sex determination means?

Answer 145

each cell decides its own sexual fate based on its sex chromosome constitution

Question 146

What are sex determination abnormalities that can occur in species where sex is cell nonautonomous and why?

Answer 146

o Although the SRY gene is considered a master sex-determining locus, other genes are involved in the sex determination cascade
 Other genes involved in production of testosterone, some acknowledge testosterone (such as testosterone receptors)
 If genes in these other pathways are interrupted, can have changes in sex determination cascades

o Sex-reversal can occur when genetic males develop as females and vice versa due to mutations in key genes in the pathway, for example:
 Translocation of the SRY gene to the X chromosome male development with 2X chromosomes
 Mutations in genes downstream of SRY XY genetic male but female development

Question 147

Describe cell nonautonomous sex determination

Answer 147

• Species where sex determination is cell nonautonomous (mammals)
o Sex determining gene controls the fate of the gonads early in development: ovaries or testes
o Gonads direct establishment of phenotypic sex through the production of hormones
o Hormones direct development of sex-specific characteristics throughout the body
 Gynandromorphs not possible

Question 148

Why is there a need for sex chromosome balance?

Answer 148

• In species with heteromorphic sex chromosomes, XX and XY individuals would express their X-linked genes at different levels, unless a special mechanism exists to control the expression of these genes

Question 149

How is sex chromosome balance achieved? Give an example animal for each mechanism

Answer 149

o In the absence of a special mechanism, XX animals and XY animals would have different levels of X-linked transcription
o Dosage compensation mechanisms have evolved that balance the level of X-linked gene products between the sexes
 Up-regulation in the expression of X-linked genes in males; in Drosophila
 Down-regulation of X-linked genes in females: in the worm C.elegans
 Complete inactivation of one of the two X chromosomes in females: in mammals

Question 150

Describe how up-regulation in the expression of X-linked genes in male Drosophila flies works

Answer 150

• Drosophila upregulate genes on the X chromosome in males: XY flies have an increased level of X-linked transcription from their single X chromosome (2 fold increase) compared to XX flies
• Dosage compensation complex (DCC), a complex of proteins and RNA molecules, is recruited to the X chromosome in males and is responsible for the increased transcription of X-linked genes

Question 151

Describe how down-regulation of X-linked genes in females in the worm C.elegans works

Answer 151

• XX worms (females) have a lower level of transcription of each X chromosome compared to XO worms (males)
• The dosage compensation complex (DCC) is recruited to both X chromosomes in XX worms, and both X chromosomes are transcribed at a lower level

Question 152

What is a Barr body?

Answer 152

condensed, inactivated X chromosome found in female nucleus

Question 153

How do you visualise a Barr body?

Answer 153

o Visible under the light microscope, with a stain that detects condensed chromatin

Question 154

How does X chromosome inactivation in a female organism work? (how X chromosome is deactivated, how many are deactivated)

Answer 154

• Only one X chromosome is transcribed in XX individuals- the other X chromosome is condensed into heterochromatin and is no longer transcribed
• Only one X chromosome is expressed in any given cell
• X-linked genes are expressed at the same level in males and females through X-chromosome inactivation dosage compensation
o Most genes are inactivated but not all

o X chromosome inactivation requires Xist
 Xist RNA coats the inactive X chromosome and recruits proteins that silence gene expression and result in chromosome condensation

• Inactivation is random (happens in 50/50 ratio)
• Once an X chromosome has been inactivated, it remains inactive through subsequent cell divisions

Question 155

When does X chromosome inactivation in a female occur?

Answer 155

• X chromosome inactivation in mammals happens early in development as cells divide: one of the two X chromosomes becomes condensed and localised to the nuclear membrane where it is not transcribed

Question 156

What is the Xist gene and what does it produce?

Answer 156

 In placental mammals, the X-inactivation-specific-transcript (Xist gene) is an RNA gene on the X chromosome
 Xist is transcribed from the X-inactivation centre of the future inactive X to produce a 17kb long non-coding RNA

Question 157

Describe X chromosome inactivation results in calico cats

Answer 157

• Example- calico cats
o Cats have an X-linked gene B that affects coat color
o In XBXb heterozygotes, some cells have the chromosome with the B allele inactivated, while other cells have the chromosome with the b allele inactivated
 XBXb heterozygotes are a mosaic, with patches of black fur and patches of orange fur (calico)

Question 158

What is the consequence of X chromosome inactivation in mammal females who have recessive disease traits

Answer 158

• Females that are carriers of X linked disease: half of their cells will have inactivated the mutant X, while half have inactivated wild-type
• In females that are ‘mosaic’ for a disease, the products of both alleles are expressed: sufficient to prevent full expression of X-linked recessive alleles in a heterozygous female
o Will have enough expression of wild-type X chromosome to take over effect of X-linked recessive allele
o Often asymptomatic or only minor symptoms of a given disorder

Question 159

What is X-inactivation skewing?

Answer 159

• X-inactivation skewing: sometimes a non-random proportion of X’s of one type are inactivated

Question 160

Where are genes found?

Answer 160

• Genes occupy physical locations (loci) on chromosomes

Question 161

What characteristic morphology do chromosomes have that can be observed under a microscope?

Answer 161

• Chromosomes have a characteristic morphology that can be observed under a microscope
o Heterochromatin and Euchromatin
o Telomere, centromere, short (p) and long (q) arms

Question 162

Do all species have the same chromosomes?

Answer 162

• Chromosomes occur in species-specific sets (karyotypes)
o Species have characteristic numbers of chromosomes with distinct sizes and morphology
o All eukaryotes have a defined number of chromosome sets int their genome
o Different species have evolved to have a different number of chromosomes

Question 163

Describe chromosomal structure (from DNA to Chromosomes)

Answer 163

o DNA is wrapped around chromosomal proteins called histones to form nucleosomes
o Nucleosomes form compact chromatin
 Histone H1 helps nucleosomes condense into 30nm fibre
o Chromatin is folded into higher-order structures that form the chromosome

Question 164

Describe the structure of nucleosomes

Answer 164

 Each nucleosome contains 146 bp DNA wrapped around histones (H2A H2B, H3 and H4).
 There is an electrostatic interaction between histones and DNA< as histone proteins are positively charged while DNA backbones are negatively charged
 This structure needs to be unfolded to allow separation of the DNA strands during gene expression or DNA replication

Question 165

Describe chromosome eukaryotic anatomy, and why each part is essential

Answer 165

o Telomeres-Mix of protein and DNA sequences at either end of the chromosomes to protect the ends from further degradation
o Centromeres- Spindle microtubules bind to the kinetochore which is formed on centromeric DNA-essential to allow chromosomes to line up during division and not get lost during cell division
 Chromosomes will line up on a metaphase plate and will be attached by a spindle formed out of microtubules
o P (short) and Q (long) arms

Question 166

What are types of chromosomes and each of their distinct features?

Answer 166

• Types of chromosomes-
o Metacentric chromosome-
 Centromere in middle
 P and Q arms are the same

o Acrocentric chromosomes-
 P arm is the short arm
 Q arm is the long arm
 Centromere is near the top of the chromosome

o Telocentric chromosomes
 There is only the q arm
 Centromere is at the top of the chromosome

Question 167

What is the animal with the smallest amount of chromosomes and the number?

Answer 167

 Smallest number of chromosomes: Jack jumper ant: 2 for females, 1 for males

Question 168

What is the animal with the largest number of chromosomes and its number?

Answer 168

 Largest number of chromosomes: agrodiae butterfly: 268 chromosomes

Question 169

What is the monoploid number (n) of chromosomes?

Answer 169

o Number of chromosomes in a basic set is the monoploid number (n)

Question 170

What is ploidy?

Answer 170

o Ploidy- the number of chromosome sets in an organism’s genome

Question 171

What is the difference between haploid, diploid and triploid?

Answer 171

 Haploid (n)- one set of every chromosome
 Diploid (2n)- two sets of every chromosome
 Triploid (3n)- three sets of every chromosome

Question 172

How is chromosomal identity and content recognised and how does this work?

Answer 172

o Chromosomes have a characteristic banding pattern
 Euchromatin contains most of the active genes
• Represented by a light stain G-banding pattern achieved through Geimsa staining
 Heterochromatin is more condensed
• Represented by a dark stain G-banding pattern achieved through Geimsa staining due to AT rich regions in that DNA that the Giemsa stain stains

Question 173

What is mitosis?

Answer 173

• Mitosis- somatic cells: chromosomes replicate once and divide once-chromosome number is maintained

Question 174

What is meiosis?

Answer 174

• Meiosis-germline cells: chromosomes replicate once and undergo 2 rounds of division to make haploid gametes: chromosome number is halved

Question 175

What are sister chromatids?

Answer 175

• Sister chromatids- basically identical to each other (except for mutations) and both replicated from the original version-DNA replication has occurred

Question 176

What are homologous pairs of chromosomes?

Answer 176

• Homologous pair- matching pair of chromosomes that have been inherited from each parent
o Chromosomes are identical in size and characteristics, have a lot of differences in their DNA sequence

Question 177

Describe the phases of meiosis and what happens at each one

Answer 177

o Chromosomes become progressively more condensed and visible during prophase I: chromosomes are synapsed (homologous chromosomes are paired together) and crossing over occurs
o Chromosomes are aligned across the middle during metaphase I
o In Anaphase I, homologues separate but sister chromatids remain together
o In Telophase I, cells separate
o Process starts again in meiosis II, but there is no pairing, no crossing over and the sister chromatids separate to produce 4 haploid products.

Question 178

What is crossing over in meiosis?

Answer 178

 Crossing over- occurs between chromatids of the two homologous chromosomes: sequences from one homologous are now on the other-transfer of genetic material

Question 179

Does crossing over only happen once on selective pairs of chromosomes?

Answer 179

No.
 Every pair of homologues crosses over at least once
 The larger the chromosome is, the more chance that recombination events occurs (multiple events can occur on one chromosome)
• Can have recombination at sister homologues, but it wouldn’t be seen because they are identical sequences

Question 180

Why does crossing over occur? Describe this process.

Answer 180

 Homologues are used as the template to repair double strand breaks
• Double stranded breaks important for keeping chromosomes paired up correctly during meiosis
• DNA synthesis to repair a double stranded DNA break
• The newly synthesised DNA is attached to the DNA molecule on the other homologue
• Gaps are repaired
• One sister chromatid has DNA sequences from each homolog
• Recombination important as it allows the chromosomes to remain together at the right times

Question 181

Where does crossing over occur? Describe why this is.

Answer 181

 Crossing over occurs at chiasmata
• Chiasmata- the sites where homologue strands exchange DNA/cross over, which occurs during prophase I
• Homologues are held together by chiasmata while pulled towards opposite poles during chromosome separation at anaphase I
o Allow separation once double stranded breaks have been repaired

Question 182

How does meiosis uphold Mendel’s law of segregation?

Answer 182

• Mendel’s 1st law, the segregation of alleles, is upheld as homologues separate during meiosis I and sister chromatids separate during Meiosis II: a gamete only has a haploid chromosome number and offspring will have diploid chromosome number

Question 183

How does meiosis uphold Mendel’s law of independent assortment?

Answer 183

• Each pair of chromosomes segregates independently during meiosis, which is the cellular basis for Mendel’s 2nd law of independent assortment

Question 184

What is spermatogenesis?

Answer 184

sperm production

Question 185

What is oogenesis?

Answer 185

egg production

Question 186

What is the difference beween spermatogenesis and oogenesis in terms of meiosis?

Answer 186

Spermatogenesis- continuous meiosis

Oogenesis- suspended meiosis between first and second stage

Question 187

Describe meiosis in oogenesis and its products

Answer 187

 First stage of meiosis occurs during embryoic development where all the eggs to be used in lifetime are made, while second phase only starts occurring when the female reaches sexual maturity
 Females are born with all of their future ova present and arrested at prophase I
 During ovulation, primary oocytes complete meiosis I and arrest at metaphase II
 Fertilised 2nd oocytes complete Meiosis II
o Only 1 of 4 products becomes an ovum, the rest become polar bodies -one precursor cell will yield one mature ovum

Question 188

What are polar bodies produced from oogenesis useful for?

Answer 188

• Genetic testing- take polar bodies and test their genotype
o If we know different alleles that are segregating in the mother, can determine whether functional oocyte inherited the good alleles if we can test that the polar body inherited the bad ones
o Polar body from Meiosis II should be the same as her functional egg
o The polar body from Meiosis 1 and the secondary oocyte (future ovum) will have different alleles

Question 189

What are variations in chromosome number caused by?

Answer 189

• Caused by problems in meiosis and gamete formation

Question 190

When does polyploidy occur, and what are two types of it?

Answer 190

• Polyploidy occurs when there is variation in the number of sets of chromosomes

• Autopolyploid
• Allopolyploid

Question 191

What is autopolyploidy and when does it occur?Give an organism example

Answer 191

o Autopolyploid- multiple copies of the same genome: single species chromosome duplication
 Occurs when the first division of meiosis fails and gives gametes without reduction in chromosome number
• Unreduced (2n) gametes fuse
• Results in either triploid (3n) or tetraploid (4n)
 Common in plants- polyploids have larger cells, hence larger plants, leaves and fruits which is desired in agriculture, but these plants are sterile

Question 192

What is allopolypoloid? Give an example.

Answer 192

o Allopolyploid- contain two (or more) different genomes after a hybridisation event: the fusion of two or more diploid genomes from different species
 Wheat is an allopolyploid of three species (which all have 7 chromosomes)

Question 193

What is aneuploidy, and two common types of aneuploidy?

Answer 193

• Aneuploidy occurs when the number of chromosomes of a particular pair is unbalanced
o Monosomy- missing one member of a pair
o Trisomy- with one extra chromosome in a pair

Question 194

What is non-disjunction?

Answer 194

• Non-disjunction- failure of chromosomes to segregate normally

Question 195

What is the result of non-disjunction?

Answer 195

o Results in daughter cells with abnormal chromosome numbers (aneuploidy)

Question 196

When can non-disjunction occur and what is the difference in results at the different times of occurence?

Answer 196

o Can occur at both meiosis I and meiosis II
 Non-disjunction at meiosis I results in one gamete that has both homologues, and one that has neither
 Non-disjunction at meiosis II yields gametes that are homozygous

Question 197

On what chromosomes can non-disjunction occur?

Answer 197

o Non-disjunction can occur for any chromosome, but is more common in sex chromosomes

Question 198

What is an example of monosomy in humans?

Answer 198

 Monosomy-one chromosome missing

• E.g. XO: Turner syndrome (2n=45)

Question 199

What are 4 examples of trisomy in humans?

Answer 199

	Trisomy- one chromosome is duplicated (2n=47)
•	XXX-triple X syndrome: Female
o	Two barr bodies
•	XXY-Klinefelter syndrome: Male
o	One barr body 
•	XYY: Male 
	Trisomy-21: Down syndrome (2n=47)

Question 200

What are rare types of trisomy, non-existent ones, and why are they rarely in population?

Answer 200

 Rare trisomy-
• Rare: trisomy 13 (Patau syndrome)
• Rare: trisomy 18 (Edward syndrome)
• Trisomy 13 and 18 don’t commonly live beyond the age of 1.
• Other trisomy types aren’t really a thing as most would be terminated before birth

Question 201

Why does incidence of trisomies increase with maternal age?

Answer 201

• Incidence of some trisomies increase with maternal age as there is increased non-disjunction during oogenesis as developing eggs are held in meiosis for a long period of time
o Division only finishes when fertilisation occurs
o The longer the eggs are paused at prophase I, the more likely that non-disjunction occurs

Question 202

Describe why trisomy 21 can occur

Answer 202

 Trisomy-21: Down syndrome (2n=47)
• Most common type of trisomy- 1/2000 live births
• During oogenesis, chromosome 21 usually has a single crossover
o If no chiasma forms, both homologues segregate to same pole at Meiosis I
o Ocasionally, chiasma at extreme ends does not provide enough resistance to tension from spindle, leading to premature pulling to the poles- recombination provides an extra timeframe to prevent premature pulling
• In 5% of cases of trisomy 21, part or all of chromosome 21 is attached to another chromosome

Question 203

What is a translocation?

Answer 203

o Translocations-partial rearrangements where an individual that carries them could be normal but can have partial sterility (due to unbalanced meiotic products)

Question 204

How do translocations occur and what are 3 different types of translocations?

Answer 204

 When segments of chromosomes break off, and attach to or exchange with other non-homologous chromosomes. Different types of translocation include:

• Reciprocal
• Non-reciprocal
• Robertsonian translocations

Question 205

What is a reciprocal translocation? Are the gametes always viable?

Answer 205

o A segment from one chromosome is exchanged with a segment from another, non-homologous chromosome, creating two translocation chromosomes
 Inviable gametes due to imbalance of genetic material- When translocated and normal chromosomes are mixed
 Viable gametes- when two translocated chromosomes or two normal chromosomes are in a gamete

Question 206

What is a non-reciprocal translocation?

Answer 206

o One piece of chromosome attaches to the other with no exchange

Question 207

What are Robertsonian translocations?

Answer 207

o Long arms of two telocentric chromosomes fuse, forming a single meta- or acrocentric chromosome
o Translocation of chromosome 29 to chromosome 1 is relatively common in European breed cattle and results in reduced fertility
o Human chromosome 2 is a result of end-to-end fusion of 2 ancestral chromosomes.
 All members of Hominidae (great apes) except humans, Neanderthals and denisovans have 24 pairs of chromosomes

Question 208

What are 2 types of chromosomal rearrangement, and whatis the impact of chromosomal rearrangment?

Answer 208

-Translocation
-Inversions
• Individuals carrying chromosome rearrangements may be phenotypically normal, but have partial sterility
o Produce unbalanced meiotic products that cause zygotes to die

Question 209

What is the ratio for codominance or incomplete dominance

Answer 209

1:2:1

Question 210

What are linked genes?

Answer 210

• Genes located on the same chromosome (called syntenic genes)
• Genes that are close together on a chromosome such that their alleles are often inherited together are considered to be linked genes

Question 211

When are genes unlinked?

Answer 211

-When they are on different chromosome or are far apart enough on one chromosome

Question 212

How do unliked genes assort?

Answer 212

Independently

Question 213

How do linked genes assort?

Answer 213

o Linked genes are not assorted independently

Question 214

What was the first genetic map and who was it created by?

Answer 214

o First genetic map was Drosophila melanogaster X chromosome map created by Sturtevant (Morgan’s student)

Question 215

How does recombination impact linked genes, gametesand genetic variation?

Answer 215

• Recombination (crossing over) seperates alleles of linked genes
• Recombination increases genetic variation by producing new alleleic combinations
• Crossing over creates parental and recombinant gametes after segregation
• This occurs more frequently between genes that are far apart

Question 216

When does recombination occur?

Answer 216

• Occurs during prophase I of meiosis
• Crossing over occurs when chromatids between two homologous chromosomes exchange DNA
• This occurs more frequently between genes that are far apart

Question 217

How do you figure out if genes are linked or unlinked? What do you do?

Answer 217

• Make a test cross to figure out if genes are linked or unlinked

Question 218

How do you make a dihybrid test cross? What is the process and result?

Answer 218

o Dihybrid test cross- F1 heterozygous X homozygous recessive individual
 Only one type of gamete is produced by the double recessive individual- the same recessive alleles are passed on to all offspring
 Four types of gametes are produced from the heterozygous parent phenotype of the test cross progeny are derived from the alleles in the gametes of the heterozygous parent
• Two gametes are parental and two are recombinant

Question 219

What is the results of the dihybrid test cross if the genes are linked?

Answer 219

• Higher ratio of parental phenotypes (resemble the parents) and a lower ratio of recombinant phenotypes (different phenotypes to the parents) if the two genes are linked
o Linked genes don’t have 9:3:3:1 ratio in dihybrid cross, and no 1:1:1:1 ratio in a test dihybrid cross
o The further two genes are apart, the more likely there will be more recombination between them and thus more recombination progeny

Question 220

What is the result of the dihybrid test cross if two genes are unlinked?

Answer 220

• If two genes are unlinked, expect 1:1:1:1 equal ratio in test cross

Question 221

How can we measure the genetic distance between linked genes?

Answer 221

Recombination rate

• Recombination frequency can be used to determine the arrangement of elements along a chromosome

Question 222

What is the formula (and units) for recombination frequency?

Answer 222

• Recombination frequency in map units (m.u) or centiMorgans (cM)= (number of recombinant offspring/Total number of offspring)*100

Question 223

How do genes more than 50 map units apart assort?

Answer 223

o Genes >50 map units apart have so much recombination between them that they are effectively unlinked an assort independently
• Cannot distinguish recombination frequencies of more than 50% from genes that are assorting independently on separate chromosomes

Question 224

How do you calculate map distance?

Answer 224

1. Generate a heterozygote
2. Perform a test cross
3. Identify parental and recombinant offspring
4. Calculate recombination frequency

Question 225

What is a genetic linkage map?

Answer 225

o Genetic linkage map- estimation of relative locations of phenotypic or molecular markers along a chromosome

Question 226

How do we link a DNA sequence to a phenotype?

Answer 226

• Use genetic mapping to link phenotypes back to sequence changes in the genome
• Connect genetic linkage maps to physical maps (DNA sequence)
o Map the gene using genetic techniques then use molecular techniques to find physical DNA sequence responsible

Question 227

Are molecular markers or phenotypic markers better for greater accuracy in genetic linkage maps?

Answer 227

 Molecular markers preferred as there are only so many genes that we can reliably characterise a visible phenotype for -pad out the map more

Question 228

Why is linkage analysis and genetic mapping useful?

Answer 228

o Identifying genes and biological processes
underlying inherited traits

o Functional genomics to discover why the gene causes the phenotype

o Genetic tests for diseases and potential cures
 Linkage mapping is important in understanding human disease because can find genetic causes of familial traits that are passed on through generations
• BRCA1 genetic mapping of breast cancer on q arm of chromosome 17
 If know genetic cause, can use that information to find a cure

o A scaffold or map to inform the assembly of whole genome sequences using genetic markers

Question 229

What are linkage groups and how do they work?

Answer 229

• Diagram of linked markers along a chromosome
• Map distances are additive
• Larger values calculated as a sum of shorter intervals

Question 230

What percentage can recombination frequency not exceed?

Answer 230

• Recombination frequency cannot exceed 50%

Question 231

How can we make linkage groups more accurate?

Answer 231

• For greater accuracy, use shorter intervals (more markers) and more offspring
o Many thousands of molecular makers can be used to fill the gaps between the limited number of visible markers due to limited number of genes that provide usable phenotypes for mapping

Question 232

What are molecular markers, how do they work and why are they useful?

Answer 232

o Are sites of silent DNA variation not associated with any measurable phenotypic variation

o Work the same way as visible markers- can be heterozygous, have recombination between them
o Are critical for understanding human variation and mapping positions of disease genes
 Amount of variation present without any phenotypic variation is particularly high in humans compared to other organisms

Question 233

How useful are molecular markers compared to phenotypic markers in bacteria? Why?

Answer 233

• In bacteria, vast majority of genome codes for protein- if there is mutations in bacterial DNA not as common to find one that doesn’t provide a phenotypic variation
o Most of the genome is exon, but a change could be a third base change, conservative substitution or redundant information
-Relatively useless

Question 234

How useful are molecular markers compared to phenotypic markers in worms/flies? Why?

Answer 234

•	In worms/flies, only 35% of genome is exon (codes for protein), but a change could be:
o	A third base change
o	A conservative substitution
o	Gene family
o	Duplicated pathways
o	Recessive alleles 
-Relatively useful

Question 235

How useful are molecular markers compared to phenotypic markers in humans? Why?

Answer 235

•	In humans, only 2% of the genome is exon, but a change could be:
o	A third base change
o	A conservative substitution
o	Gene family
o	Duplicated pathways
o	Recessive allele
-Extremely useful

Question 236

What are 3 types of common molecular markers?

Answer 236

o	SNPs (single nucleotide polymorphisms)
o	RFLPs (restriction fragment length polymorphisms)
o	Microsatellites (short tandem repeats)

Question 237

What are single nucleotide polymorphisms?

Answer 237

 Single nucleotide differences in DNA sequence

Question 238

Are SNPs common?

Answer 238

 Most common type of molecular change between individuals

Question 239

Do SNPs impact phenotype?

Answer 239

• Differences in DNA sequence may or may not be associated with differences in protein structure or phenotypes

Question 240

How can SNPs be identified?

Answer 240

• Sequencing (e.g. whole genome sequencing) but is expensive
• Microarray chip (SNP array)-most common method

Question 241

How can the microarray chip be used to detect SNP variation?

Answer 241

o Microarray chip containing spots of DNA oligonucleotide probes, to detect sites of known SNP variation in the genome
1. Attach a single stranded oligonucleotide (40-60 bp in length) corresponding to one variant to one feature on the microarray and single-stranded oligonucleotide corresponding to the other variant to another feature on the microarray
2. Prepare genomic DNA from the individual being tested
3. Label with fluorescent dye
4. Hybridise to the microarray (sites of known variation)
o If there is DNA binding between oligonucleotide and microarray , then there is fluorescence-means that SNPs match up and we know what SNPs the individual has by the number of fluorescent spots they have

Question 242

What are RFLPs (restriction fragment length polymorphisms) and what do they result from?

Answer 242

 Nucleotide differences that generate a change in a restriction enzyme cutting site
 SNP variations can destroy or create restriction enzyme recognition sequences

Question 243

How can restriction fragment length polymorphisms identify SNPs?

Answer 243

 Differences in DNA cutting sites results in different sized bands after a restriction digest on agarose gel-> can identify whether SNPs occurred or not based on size of restriction digest

Question 244

What are microsatellites?

Answer 244

 2-5 nucleotides tandemly repeated in a DNA sequence

Question 245

Why are microsatellites useful as a molecular marker?

Answer 245

 These repeats occur in conserved regions of the genome so can use PCR primers to detect this region of the genome but within the microsatellite the repeat sequences will differ in number
 Number of repeats in microsatellite DNA sequences are variable within the allele of individuals
 Amplify microsatellite alleles with PCR
• Size of PCR product produced changes with number of microsatellite repeats
o Can be used to detect paternity

Question 246

Describe how to perform a trihybrid test cross and what is involved in each step

Answer 246

o Step 1: Determine if the genes are linked
 8 possible phenotypic combination
 If not linked, then 1:1:1:1:1:1:1:1
 If partially linked, see 4 big number categories and 4 small ones
 If linked, then there is deviation in that ratio
• Three categories
o Highest frequency category- parental test cross phenotypes (because recombination is rare event)
o Intermediate frequency category-Single recombination event
o Lowest frequency category-Double recombination event (middle marker has switched chromosomes independent of the ages)

o Step 2: Determine gene order
 Look for double crossover classes- the classes with the fewest recombinants (the lowest number)
 The marker that is different from the parental configuration is the middle marker

o Step 3: Look at markers in pairwise configurations
 Factor in double recombination events between flanking markers
• Double recombinants added in calculation twice
o Don’t do this if there is no clear double-recombinant class
 Unlinked genes give 50 or more map units

o Step 4: Put the map together

Question 247

Why are trihybrid test crosses done?

Answer 247

o Determine if 3 genes are linked, the gene order and the map distance

Question 248

Describe a trick which may be used in exams through notation of linkage in crosses

Answer 248

 Notation in exams-
• Even if notation is linkage location:
o Do not assume all genes are linked
o Do not assume that the order of writing is the order of the genes on the chromosome

Question 249

Why can recombination rate vary throughout the genome?

Answer 249

o Chromatin structure
o Sex differences
o Chromosome aberrations

Question 250

What are hotspots?

Answer 250

 Hotspots-high levels of recombination

• Greater genetic distance relative to physical distance

Question 251

What are coldspots?

Answer 251

 Coldspots-low levels of recombination

• Shorter genetic distance relative to physical distance

Question 252

Why do hotspots and coldspots exist?

Answer 252

o DNA in coldspots doesn’t cross over so well due to the proteins surrounding that DNA e.g. genes separated by a centromere
——Pericentric heterochromatin

 May be due to the feasibility of DNA in those regions to initiate crossing over

Question 253

What is pericentric heterochromatin?

Answer 253

 Pericentric heterochromatin-condensed chromatin at the centromere which lacks standard meiotic recombination (no recombination here)

Question 254

Are recombination rates the same for both men and women?

Answer 254

 Recombination rates differ between males and females for most animals

Question 255

Describe the recombination rates in male and female drosophila, and why these rates differ

Answer 255

• In male fruit flies, there is no crossing over at all
o Unusual prophase I of meiosis in which no chiasmata develop presumably due to lack of expression of recombination proteins which usually help this recombination to occur

Question 256

Describe the recombination rates in male and female humans, and why these rates differ

Answer 256

• Genetic distance and maps on human male and female chromosomes can look different
o Females have slightly more recombination than males
o Probably because males vs females have different tissues and different gamete production rates

Question 257

What is inversion?

Answer 257

 Inversion- a type of chromosome aberration, a structural variation in a chromosome leading to rearrangement of chromosome segments
• Piece of chromosome breaks up and flips around and inserts in the opposite orientation of its original orientation

Question 258

Describe the impact of inversion on sterility

Answer 258

 Heterozygous individuals for inversion chromosomes may be phenotypically normal, but have partial sterility
• Produce unbalanced meiotic products if recombination occurs within the inversion

Question 259

What are the two types of inversions?

Answer 259

 Inversions can be paracentric (include centromere) or pericentric (no centromere)

Question 260

Describe how recombination occurs in an inversion heterozygote, the products of this recombination and what can change the products

Answer 260

• During meiosis, for genes to align together, a loop needs to form (all markers paired up with each other)
• Products of single recombination mean that there are ½ viable and ½ inviable chromomes
o Dicentric-Have two centromeres
o Acentric-Have no centromeres
• Double recombination events can restore viability to a chromosome

Question 261

What is a physical map?

Answer 261

• Physical map- position of markers in the DNA sequence (in megabases)

Question 262

What is a genetic map?

Answer 262

• Genetic map- position of markers in linkage group (in map units)

Question 263

What is the recombination rate and how do we interpret a graph of recombination rate?

Answer 263

• Recombination rate (megabases per map unit)- differs along chromosomes
o Linear line- no recombination hotspots/coldspots in chromosome
o Non-linear line: recombination results in high rate whilst no recombination results in stationary points

Question 264

What does genetic mapping of traits use?

Answer 264

• Genetic mapping of traits uses natural genetic variation of individuals in a population

Question 265

What is a haplotype, how do they happen and what can they be?

Answer 265

• Haplotype- a group of alleles that are inherited together throughout generations
o A block of alleles in a set of linked loci that are inherited together
o These alleles will tend to be passed on together during meiosis, unless separated by recombination
o May consist of any type of genetic variation:
 SNPs
 Phenotypic markers
 RFLPs
 Microsatellites

Question 266

What usually happens to a causal mutation that leads to a trait throughout the generations in terms of inheritance patterns?

Answer 266

• A causal mutation that leads to trait:
o Inherited with other nearby variants on the chromosome
o Recombination can generate blocks of variation that tend to be inherited with a mutation of interest
o Recombination reduces large blocks transmitted through the pedigree
o Variation that happened to be linked to a causative mutation will still be associated with the mutant many generations later

Question 267

What are ancestry haplogroups and what can be used to detemrine them?

Answer 267

o Ancestry haplogroups- A group of similar haplotypes that share a common ancestor
 Indicate likely similar origin or line of descent
 Genome-wide SNP analysis can determine ancestry haplogroups

Question 268

How can the fact that linked alleles and haplotypes stay together for generations be used to identify variation linked to phenotypic traits?

Answer 268

 Positional cloning

 Genome Wide Association Studies (GWAS)

Question 269

Describe the purpose and concept of positional cloning

Answer 269

• Technique (used a lot in the 1980s) to locate position of a gene along the chromosome
• Use genetic mapping to connect between the gene that affects the phenotype and the DNA sequence
o DNA sequence for a gene can be identified based on its genetic map position
• Mapping done by observing individuals in a pedigree, checking suite of molecular markers for these individuals and finding area of the genome which always comes up with same markers that are variable in mutated individuals. Then, can look at region of DNA between them

Question 270

Describe how positional cloning is performed

Answer 270

• Step 1: Gene of interest is mapped between two cloned markers
o Map the phenotype by recombination between known molecular markers
• Step 2: The DNA between the markers is isolated and analysed
• Step 3: The compatible candidate gene is identified based on
o Expression pattern (expression at right tissues at right time)
o Evolutionary comparisons-compare with other organisms to see if gene has the same function in those other organisms
o Sequence analysis-see if it differs from wild type individual

Question 271

Describe an example of positional cloning performed to map a disease

Answer 271

• First example of positional cloning is mapping of cystic fibrosis gene in 1989
 Cystic fibrosis was mapped to a region on 7q31
 A region that was conserved in mammals was isolated
 A cDNA from this region was isolated
 This cDNA was used to probe for transcripts from tissues affected in CF patients
 Found that gene expressed in all tissues affected by cystic fibrosis and became candidate for causing the disease

Question 272

Describe the genetic basis of cystic fibrosis

Answer 272

o Common autosomal recessive disorder, affecting lungs and other organs and tissues that produce sweat, digestive fluids or mucus
o Extensive pedigrees available
o Gene located on chromosome 7 in 1000bp interval

Question 273

Describe how genome wide association studies are performed and their purpose

Answer 273

• Sequencing is more accessible
• SNPs used
• Compare genome-wide SNP variation in of thousands of affected vs unaffected individuals
• Relative frequencies of each SNP and haplotype are calculated and plotted among affected and unaffected individuals
• Can identify SNPs associated with a disease, but they cannot specify which genes are causal
• SNPs and haplotypes that are more common among affected individuals identify candidate locations for causative alleles for the trait
• Genomic locations can be surveyed for candidate causative genes based on gene function, expression patterns, similarity to mutants in other animals…

Question 274

How can GWAS-Manhattan plots be interpreted?

Answer 274

• Interpreting GWAS-Manhattan plots
o Each dot represents a haplotype, a region containing variable SNPs
o Each number on the X axis represents a chromosome
o Each colour indicates when chromosome changes
o Probability that a haplotype is associated with the trait is located on the y axis
o SNPs/haplotypes with a significant association with the trait are highlighted in a different colour (green)

Question 275

How can genes be surveyed as candidate causative genes?

Answer 275

o Expression pattern- from transcript analysis such as RNA sequencing and microarrays
 Which genes are expressed in the appropriate time and location
o Evolutionary comparison
 Has the gene been identified with a phenotype in other closely related organisms?
o Mutations and polymorphisms- Do people affected by the trait share a DNA sequence variation in one of these genes?

Question 276

What is the use of insecticides and how do they work?

Answer 276

• Modern agricultural practices rely on chemical methods of pest control
• Compounds that act as insecticides have diverse chemical structures with different modes of action but a lot of them target nervous system of insects
o E.g. pyrethrins, neonicotinoids, DDT, dieldrin
 Disrupt nervous system of arthropods, causing paralysis and death

Question 277

What are the problems of insecticide use?

Answer 277

• Problem of insecticide use-
o Puts pest species under intense selective pressure
o Variants containing mutations in genes that provide resistance (ability to tolerate insecticide) are favoured
o Resistance is selected for in a population and becomes widespread

Question 278

Describe dieldrin and the problem with its use

Answer 278

o First used in 1950s
o Insect-specific neurotoxic chemical
o Dieldrin- a synthetic chemical with high insecticidal activity
o Resistant populations developed quickly
 Present in pests of medical and agricultural significance
 Crop pests and vectors of disease

Question 279

Describe the resistance capability of insects with the Rdl gene depending on their genotype

Answer 279

o Unknown cause of the resistance phenotype
 Resistant homozygotes survive much higher doses (4000 fold higher doses) than wild-type homozygotes
 Heterozygotes survive at intermediate levels

Question 280

What is the downside of an insect being resistant to dieldrin?

Answer 280

o Resistance to this chemical shows temperature sensitivity
 When exposed to high temperatures (380C), resistant homozygotes (RR) exhibit higher sensitivity than wild-type homozygotes (SS)
• Heterozygotes (RS) have intermediate levels of temperature sensitivity
 Resistant flies will go into heat shock (go to sleep in a while and eventually die)
 Recovery times of resistant mutants is much longer (10 minutes) than wild type flies (5 minutes)

Question 281

Describe how the mutation responsible for dieldrin resistance was found

Answer 281

• Backcross and linkage mapping with 2 markers
o Bristle phenotype- stubble (position 58.5)
o Lyra wings (position 40.5)
• Rdl (resistance to dieldrin) was mapped on position 25 on chromosome 3
 Further refining of location of causal mutation with positional cloning
• Screened lots of different markers along chromosome to lead to identification of region containing the resistance gene
• Resistance mapped to a locus containing the first identified insect ligand-gated chloride channel gene

Question 282

Where is the Rdl gene and what does it code for?

Answer 282

• Rdl (resistance to dieldrin) was mapped on position 25 on chromosome 3
• Resistance mapped to a locus containing the first identified insect ligand-gated chloride channel gene

Question 283

Describe the molecular function of Rdl gene in wild-type individuals

Answer 283

 Normal-
• Ligand-gated chloride channel with large extracellular domain that binds to GABA (an excitatory ligand) and allows for chloride ion influx to flow through
o Five Rdl subunits join together to make a chloride channel pore in the membrane

Question 284

What is the impact of insecticide dieldrin on the the Rdl gene?

Answer 284

• Insecticide dieldrin blocks chloride influx

Question 285

Why are mutants in the Rdl gene resistant to dieldrin?

Answer 285

• Single nucleotide polymorphism (SNP)-> G to T mutation which results in an amino acid change in transmembrane region of the protein (alanine to serine substitution at position 301)
• Mutant receptor no longer binds to dieldrin
o Chloride channel is not blocked by insecticide
o Insects survive

Question 286

Describe how it can be observed whether insect populations have the Rdl mutant gene for dieldrin resistance.

Answer 286

o Mutation screening-see how many populations around the world have this mutation
 G to T SNP that leads to resistance generates an RFLP and removes HaeII recognition site
 PCR performed on fragment
 Restriction enzyme HaeII cuts twice in wild type individuals but in resistance mutants only gets cut once: therefore different banding pattern can be seen
• Uncut fragment- 268 bp
• Homozygous resistant- 205 and 63 bp
• Homozygous susceptible mutant- 3 bands
• Heterozygote- all bands present in either allele
 HaeII method used to recognise mutants around the world

Question 287

Describe the Tasmanian devil in terms of:

• type of mammal
• location
• chromosomes

Answer 287

• Tasmanian devil-
o World’s largest carnivorous marsupial, distribution now restricted to Tasmania
o Has 7 different chromosomes

Question 288

What is the Tasmanian devil face tumour disease and how and when was it spread?

Answer 288

• Tasmanian devil face tumour disease-
o Transmissible cancer that can spread like a contagious disease
o Spread by the transfer of living cancer cells by biting
o Spread throughout Tasmania since first identified in 1996

Question 289

How do we known that the tasmanian devil face tumour disease is a transmissable cancer?

Answer 289

o Fatal transmissible cancer is decimating the devil population in Tasmania
 All DFTD cells are genetically identical to each other and genetically distinct from their hosts own cell
• Seen by using genetic markers and karyotyping

Question 290

How did the tasmanin devil face tumour disease originate?

Answer 290

 Cancer originated from a single individual and spread, rather than arising repeatedly
• First strain in 1996 (female origin)
• New strain identified in 2015 (male origin)
o Tumor cells must have arisen from a female because they contain X-chromosome fragments

Question 291

Describe the karyotype of tumour cells in tasmanian devil face tumour disease when compared to normal cells

Answer 291

o There are translocations, deletions, rearrangements…
o Chromosome 1 and sex chromosomes missing from tumor karyotypes
 Translocations and joining from different chromosomes
o Chromosome 5 aneuploid
o Four additional marker chromosomes (M1-M4) are present, made up of chromosome fragment translocations, probably inversions and other chromosome abnormalities
 Not additional chromosomes-just have been formed from bits of pre-existing chromosomes

Question 292

How were karyotype differences highlighted in tumour cells in tasmanian devil face tumour disease?

Answer 292

o Fluorescence labelling of chromosomes highlights karyotype differences
 Label then look under a microscope

Question 293

Describe the process of Crawford et al’s 2017 study:

Loci associated with skin pigmentation identified in African populations

Answer 293

• Genome-wide association study and functional characterisation of novel genes involved in human skin pigmentation
• Studies often focus on European lineages
• Large diversity of pigmentation phenotypes within Africa
o Melanin index- skin tone measurements
o Erythemal dose- level of radiation required to turn skin red
• Compared populations to each other using those phenotypes
• Look at Africans as baseline for rest of population
o Measure phenotypic diversity (pigmentation levels)
o From blood, isolate DNA
 Analysed 1,570 DNA samples of Africans with diverse pigmentation phenotypes
o Genotyping using SNP array
 Illumina Omni5M exome array about 4.3 million SNPs
• SNPs from international HapMap and 1000 genomes projects
o Association between genetic variation and the trait
 Manhattan plot of GWAS
 Then functionally characterised each gene to make sure they had function for skin pigmentation-functional gene experiments necessary to confirm causative genes once associations have been found

Question 294

Describe the results of Crawford et al’s 2017 study

Answer 294

• GWAS identified novel variants associated with skin pigmentation
• Significant variants clustered in 4 genomic regions that together account for about 30% of the phenotypic variation
• Four regions identified account f about 30% of variation in skin pigmentation phenotype
o SLC24A5, MFSD12, DDBI and HERC2

• Proved phenotype of candidate genes with functional experiments in model organisms
o MFSD12- codes for a protein that modifies pigmentation in human melanocytes
 Decreased MFSD12 expression associated with darker pigmentation
 Genetic knockouts of MFSD12 orthologues affect pigmentation in mice

• Identified previously uncharacterised genes associated with skin pigmentation in ethically diverse Africans

Question 295

What are gene interactions possibly involved in skin pigmentation?

Answer 295

o Gene interactions possibly involved:
 Complementary gene interactions (both genes needed for phenotype)
 Duplicate gene interaction (either gene needed for phenotype/redundancy)
 Dominant gene interaction (genes with same phenotype interact additively)
 Epistasis (one gene stops/masks the phenotype of another)
• These genes have diverse functions
o Repairing UV damage: melanogenesis in skin cells

Question 296

What is the type of evidence necessary to confirm causative genes once an association has been identified?

Answer 296

• Gene expression analysis
• Molecular function of candidate gene
• Functional experiments in model organisms