5, 6

Question 1

issues with Mendel’s laws

Answer 1

• incomplete dominance and codominance
• multiple alleles
• pleiotropy
• variable expressivity
• incomplete penetrance
• environmental influence

Question 2

how do we know that dominance is not always complete?

Answer 2

crosses between true-breeding strains can produce hybrids with phenotypes different from both parents

Question 3

incomplete dominance

Answer 3

• F1 hybrids that differ from both parents express an intermediate phenotype
• neither allele is dominant nor recessive to the other
• the heterozygous phenotype is distinct from either homozygous phenotype (an intermediate phenotype)
• phenotypic ratios are the same as genotypic ratios

Question 4

codominance

Answer 4

• F1 hybrids express the phenotype of both parents equally
• phenotypic ratios are same as genotypic ratios
• both alleles are expressed in the heterozygotes

Question 5

draw a table portraying a summary of dominance relationships

Question 6

give an example of incomplete dominance in plants

Answer 6

Antirrhinum majus (snapdragons)
P: red x white
F1 (all identical): pink x pink
F2: 1 red: 2 pink: 1 white
- the genotypic and phenotypic ratios are the same
- this signifies that the alleles of a single gene determine these 3 colours

Question 7

give an example of incomplete dominance in animals

Answer 7

whippets:
- DNA testing has recently identified a mutation on the myostatin gene that tends to make whippets with one copy fast and whippets with two copies overmuscled ‘bullies’

Question 8

give an example of incomplete dominance in humans

Answer 8

familial hypercholesteraemia
- results in abnormally high levels of cholesterol
- the general population (homozygous for fh) have <250mg/dl of plasma cholesterol
- heterozygotes for FH have 250-500
- homozygotes for FH have >500

Question 9

can a gene have more than two alleles?

Answer 9

• genes may have multiple alleles that segregate in populations
• although there may be many alleles in a population, each individual carries only 2 of the alternatives

Question 10

give an example of a gene that has more than two alleles

Answer 10

• ABO blood group gene: I
• 3 alleles: IA, IB, and i
• 6 possible ABO genotypes: IAIA, IBIB, IAIB, IAi, IBi, or ii

Question 11

dominance relations are unique to

Answer 11

a pair of alleles; dominance or recessiveness is always relative to a second allele

Question 12

dominance relations in the ABO blood group gene

Answer 12

• IA and IB are completely dominant to i but codominant to IB

Question 13

how many possible phenotypes are there for blood type?

Answer 13

4: type A, type B, AB, or O

Question 14

how is the ABO gene an example of codominant alleles?

Answer 14

the ABO gene encodes a cell surface protein, glycosyltransferase (an enzyme)

A allele: A antigen
B allele: B antigen
O allele: does not produce any antigens

• A and B antigens may be present on the same cell
• Alleles A and B are codominant

Question 15

lentil coat pattern alleles are an example of

Answer 15

codominant alleles

Question 16

describe the genetic mechanisms underlying lentil coat patterns

Answer 16

S allele: spotted
D allele: dotted

P: CSCS x CDCD
F1 (all identical): CSCD x CSCD (spotted/dotted)
F2: 1 CSCS (spotted): 2 CSCD (spotted/dotted): 1 CDCD (dotted)

Question 17

draw a table of blood type and antibodies in serum

Answer 17

O is universal donor

Question 18

draw a table of blood type of recipient vs compatibility with donor blood type

Answer 18

AB is universal recipient

Question 19

how do we establish dominance relations between multiple alleles of a gene?

Answer 19

perform reciprocal crosses between pure-breeding lines of all phenotypes and observe the phenotype of the F1 heterozygote/hybrid

Question 20

dominance series of agouti gene

Answer 20

A-: agouti
atat: black/yellow
aa: black
ata: black/yellow

A>at>a

Question 21

pleiotropy

Answer 21

single gene determines more than one distinct and seemingly unrelated characteristics, controlling several functions and having many symptoms

Question 22

some alleles may cause lethality. what does this mean?

Answer 22

type of pleiotropy where alleles produce a visible phenotype and affect viability: alleles that affect viability often produce deviations from a 1:2:1 genotypic and 3:1 phenotypic ratio predicted by Mendel’s laws

Question 23

explain why lethality-causing alleles deviate from Mendelian ratios

Answer 23

• Mendel’s laws assume all genotypes are viable and equally fit.
• however, when an allele causes lethality, the affected genotypes drop out of the population, skewing the observed ratios.

Question 24

King George 3rd’s ‘madness’

Answer 24

porphyria variegata
- caused by a mutation in the gene for the heme biosynthetic pathway, which encodes an enzyme
- if the enzyme is missing, porphyrin accumulates, resulting in concentrations that are high and toxic to organisms
- leads to multiple effects across urine (dark red urine), digestive system (abdominal pain and constipation), muscles (rapid pulse and weak limbs), and nervous tissue (stupor, delirium, convulsions, mad behaviour)

Question 25

inheritance of coat colour in mice as an example of lethality

Answer 25

AA: agouti AyA: yellow - Ay is dominant to A - yellow mice must be AyA - inbred agouti (AA) x yellow (AyA) yields 1:1 agouti:yellow - yellow AyA x yellow AyA mice do not breed true - Ay is a recessive lethal allele (negatively affects survival of homozygote) - AyAy die in utero and do not show up as progeny

Question 26

coat colour in mice shows the importance of avoiding

Answer 26

consanguineous mating

Question 27

draw a table summarising Mendel's basic assumptions and a comparison of these assumptions with 20th century contributions

Question 28

sickle cell anaemia

Answer 28

- haemoglobin is composed of four polypeptide chains: 2 alpha (α) globin chains, and 2 beta (β) globin chains - SCA is caused by a point mutation in the Hbβ gene, which encodes the β-globin subunit - normal wild-type is Hbβ^A - ~400 mutant alleles have been identified so far - Hbβ^s allele specifies abnormal peptide causing sickling among RBCs, which are usually biconcave - Hbβ^s allele is codominant at the molecular level and recessive at the phenotypic level (Hbβ^A is haplosufficient) - pleiotropy: Hbβ^s allele affects more than one trait (sickling, resistance to malaria, recessive lethality) - RBCs are much more fragile and easily broken, leading to a lower lifespan and anaemia

Question 29

how do sickle cells confer resistance to malaria?

Answer 29

infected RBCs break up, or are cleared by the spleen before Plasmodium Falciparum has a chance to reproduce and lyse the cells

Question 30

draw a table analysing the phenotypes at different levels of analysis for sickle cell anaemia

Question 31

variable expressivity

Answer 31

a phenotype that varies in intensity

Question 32

example of variable expressivity

Answer 32

individuals with the same genotype for cystic fibrosis have varying levels of symptoms

Question 33

incomplete penetrance

Answer 33

the phenotype is not always observed among individuals carrying the genotype

Question 34

example of incomplete penetrance

Answer 34

DD or Dd only result in 80% polydactyly

Question 35

opposite of variable expressivity

Answer 35

unvarying expressivity

Question 36

define penetrance

Answer 36

% of individuals with a genotype that express the phenotype

Question 37

why do penetrance and expressivity vary?

Answer 37

- genetic modifiers: other genes (outside the main disease gene) that influence the severity, onset, or presence of a trait - environmental factors: may act as modifiers

Question 38

complete penetrance and unvarying expressivity

Question 39

incomplete penetrance and unvarying expressivity

Question 40

complete penetrance and variable expressivity

Question 41

incomplete penetrance and variable expressivity

Question 42

give an example of variable expressivity

Answer 42

coat spots/colour on dogs (slide 26)

Question 43

give an example of variable expressivity due to environmental modification

Answer 43

siamese cats are usually homozygous for a mutant form of an allele of the TYR gene that controls melanin production, but is only functional at cooler temperatures. warmer temperature: colourless precursor -> enzyme nonfunctional -> no melanin -> light fur cooler temperature: colourless precursor -> enzyme functional -> melanin -> dark fur thus, the legs, tail, ears, nose are usually darker in colour (exposed to cooler temperatures), whilst the main body is white.

Question 44

why do variations on dominance relations not negate Mendel's law of segregation?

Answer 44

- dominance relations affect phenotype as the gene products control expression of phenotypes differently - alleles still segregate randomly during gamete formation

Question 45

complementation

Answer 45

occurs when two individuals with mutations in different genes (but causing the same phenotype) are crossed, and their offspring have a normal (wild-type) phenotype.

Question 46

complementation genetics assumes that the mutation is ------

Answer 46

recessive

Question 47

Astyanax mexicanus

Answer 47

- cave fish descended from surface subspecies, but accumulated mutations in genes required for sight, making them blind. cave 1 x cave 1: F1 blind cave 1 x cave 2: F1 can see cave 1 x cave 3: F1 can see - deficient copies in one lineage were compensated for by the functional copies in the other lineage (complementation) - this suggested that although the fish in different caves had all converged upon the same outward appearance (blindness), they had taken different evolutionary paths to do this and had acquired mutations in different genes responsible for sight - this showed that there are many steps to producing an eye, and that different subspecies have mutations in different steps/pathways required for eye development

Question 48

what two possibilities do we have to distinguish between when discussing the effect of mutation on phenotypes?

Answer 48

1. mutations in the SAME gene can give rise to the same phenotype 2. mutations in DIFFERENT genes can also give rise to the same phenotype

Question 49

allelic

Answer 49

alleles of the same gene

Question 50

how does one WT allele and one mutant allele result in a restoration of function?

Answer 50

the wild type allele is haplosufficient so complements the mutant alleles (compensates for what the mutant is lacking) so that the phenotype is wild type.

Question 51

how do we distinguish between complementation and allelism?

Answer 51

- complementation: (WT, M) the wild type allele is haplosufficient so complements the mutant alleles (compensates for what the mutant is lacking) so that the phenotype is wild type. - allelism (M, M) two mutant alleles cannot complement each other so the phenotype is mutant

Question 52

molecular vs phenotypic visibility of allelism

Answer 52

while the locus appears heterozygous at the molecular level (the two mutant alleles are caused by different base pair substitutions), the individual appears homozygous at the phenotypic level (they express the mutant phenotype to the same degree)

Question 53

history of tomatoes and why they are good genetic models

Answer 53

- domesticated in south and Central America, ~5000 years ago - brought by the conquistadors to Europe sometime between 1521 and 1544 - pomi d'oro (golden apples) and pomp d'amour (apple of love) - by 1622, 4 varieties - red, yellow, orange, golden - by 1700, 7 varieties - long history of breeding - good genetic model

Question 54

purpose of testing for allelism

Answer 54

interested in finding genes responsible for a particular trait

Question 55

forward genetics experiment

Answer 55

You observe or induce a mutant phenotype and then work forward to discover which gene(s) caused it (phenotype -> gene)

Question 56

process of testing for allelism or complementation

Answer 56

1. expose a purebred wild type to mutagenesis 2. isolate pure-breeding lines of mutants that express the mutant trait of interest 3. cross the mutants together and observe the phenotypes of the F1, F2, Fn progeny

Question 57

if allelism is the case

Answer 57

- the F1, F2, and Fn progeny will all express the mutant phenotype - mutant 1 and mutant 2 had the same gene affecting tomato colour

Question 58

if complementation is the case

Answer 58

- the F1 progeny will have the wild type phenotype; they are heterozygous for mutant and wild type alleles - Mutant 1 and mutant 2 contained different genes affecting the same trait, with mutant 1 containing mutations in one gene and mutant 2 containing mutations in the other

Question 59

complementation testing

Answer 59

- one of the most powerful tests in genetic analysis - simultaneously a test for allelism (must be one or the other) - works when the mutant phenotype is recessive - allows us to uncover how many different genes control a trait

Question 60

draw a flow chart of the two possible outcomes for a complementation/allelism test

Answer 60

wild type -> mutant 1 x mutant 2: 1. F1 progeny: mutant (allelic - mutants uncover 2 alleles at 1 locus) 2. F1 progeny: wild type (complementation - mutants uncover 2 loci controlling the same trait)

Question 61

give two examples of complementation in humans

Answer 61

1. if two non-hearing parents with mutations in DIFFERENT hearing genes have children, complementation will occur and all the F1 progeny will be able to hear (AAbb x aaBB -> AaBb) 2. if two parents with ocular-cutaneous albinism (OCA) with mutations in DIFFERENT determining genes have children then complementation will occur and the children will not have OCA (aaBB x AAbb -> AaBb)

Question 62

when we know that two genes are acting on the same trait, how do we find out whether they are functioning in the same pathway?

Answer 62

1. take two mutant lines, M1 and M2, and cross them together (aaBB x AAbb) 2. create a dihybrid/heterozygous line (AaBb), resulting in a restoration of WT phenotype due to complementation 3. conduct a dihybrid cross (F1xF1)

Question 63

recessive epistasis

Answer 63

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1(aabb) phenotype ratio: 9 (A_B_): 3 (A_bb): 4 (aaB_ and aabb) aa is epistatic to B and b - when homozygous, recessive allele of one gene masks both alleles of another gene

Question 64

epistasis

Answer 64

epistasis occurs when one locus masks the effects of another locus acting on the same trait. the locus that is doing the masking is said to be epistatic to the other

Question 65

epistatic ratios allow a geneticist to hypothesise about

Answer 65

the order of genes in a particular pathway; in a biosynthetic or biochemical pathway, the epistatic gene encodes an upstream step

Question 66

upstream step

Answer 66

earlier in the pathway

Question 67

example of recessive epistasis in animals

Answer 67

slide 27

Question 68

example of recessive epistasis in humans

Answer 68

- all type A, type AB, type B, and type O people are H- - people with hh genotype will appear to be type O regardless of their l locus genotype - gene for substance H is epistatic to the l gene (hh is epistatic to all combinations of l alleles, except for ii)

Question 69

complementary gene action/reciprocal recessive epistasis

Answer 69

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1 (aabb) phenotype ratio: 9 (A_B_): 7 mutants (A_bb and aaB_ and aabb) aa is epistatic to B and bb is epistatic to A - when homozygous, recessive allele of each gene masks the dominant allele of the other gene

Question 70

example of complementary gene action/ reciprocal recessive epistasis in a plant

Answer 70

slide 31

Question 71

dominant epistasis 1

Answer 71

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1 (aabb) phenotype ratio: 12 (A_B_ and aaB_): 3 (A_bb): 1 (aabb) B is epistatic to A and a. when dominant allele of one gene hides both alleles of the other gene

Question 72

give an example of dominant epistasis 1 in plants

Answer 72

slide 33

Question 73

dominant epistasis 2

Answer 73

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1 (aabb) phenotype ratio: 13 (A_B_ and aaB_ and aabb): 1(A_bb) B is epistatic to A. when dominant allele of one gene hides effects of dominant allele of other gene.

Question 74

give an example of dominant epistasis 2 in chicken

Answer 74

slide 35

Question 75

do mendelian laws of segregation and independent assortment still apply with gene interactions?

Answer 75

yes.