so far

Question 1

What were the two hypotheses to explain inheritance in 1837?

Answer 1

1. one parent contributes more to an offspring’s inherited traits (eg Aristotle contended that it was the male and that a fully formed homunuculus was inside the sperm)
2. blended inheritance - the traits of the parents are blended in their offspring (like blue and yellow to make green) - explained single offspring, but not siblings, or the next generation

Question 1

5 characteristics of a model organism:

Answer 1

1. short generation time
2. can be inbred (self-fertilise)
3. simple reproductive biology
4. small size
5. large numbers of progeny for robust statistical analysis

Question 2

why was Pisum sativum a good choice for Mendel’s experiments?

Answer 2

• Well characterized, cultivated plant, grew well in Brno
• Could be self-fertilized (selfed) - pollen from the plant could be used to
  pollinate its own flowers - allows inbreeding
• Could obtain and maintain pure-breeding lines - these always bred
  true producing the same trait generation upon generation
• Could be readily cross-fertilized to create hybrids between pure-breeding
  lines - could have carefully controlled matings and reciprocal crosses - to
  rule out the effect of one parent versus the other
• Could examine clear-cut (qualitative/discrete) traits where there were 2 forms of the trait- “either-or” choices - unambiguously distinguish forms of the trait
• Could have a large number of plants and progeny, so could subject the
  data to statistical analysis - Mendel did quantitative analyses that produced
  robust results and aided interpretation

Question 3

The August Krogh Principle

Answer 3

For many problems there is an animal on which it can be most conveniently studied

Question 4

what is a reciprocal cross?

Answer 4

a breeding experiment where two different parental strains are crossed twice, with the sex of the parents switched in the second cross

Question 5

process of cross-pollination of pea plants

Answer 5

1. pollen transferred from one pea plant to the stigma of recipient pea plant (with anthers previously removed) with brush
2. seed forms and germinates

Question 6

process of selfing of a pea plant

Answer 6

transfer of pollen onto stigma of same plant

Question 7

examples of antagonistic pairs that Mendel investigated

Answer 7

• seed colour (yellow/green)
• seed shape (round/wrinkled)
• flower colour (purple/white)
• unripe pod colour (yellow/green)
• ripe pod shape (round/pinched)
• stem length (long/short)
• flower position (axial - along stem/terminal - at tip of stem)

Question 8

broad overview of process of Mendel’s investigation

Answer 8

1. isolated pure forms of each trait
2. crossed 2 pure breeding lines that differed at one trait only
3. looked at progeny (F1 and F2)

Question 9

how did dominance manifest itself in Mendel’s experiments?

Answer 9

one of the two traits in an antagonistic pair was dominant and would always be manifested in the F1 hybrid

Question 10

dominant antagonistic traits in Mendel’s experiments

Answer 10

• yellow
• round
• purple
• green
• round
• long
• along stem - axial

Question 11

how did Mendel disprove the theory of uniparental inheritance and demonstrate that both contribute equally?

Answer 11

reciprocal crosses revealed that not only were traits dominant but also that this was independent of the parent

‘it is immaterial to the form of the hybrid which of the parental types are used in the cross’

Question 12

define a locus

Answer 12

a genetically defined location - strictly speaking, we don’t know if it is only one gene or not - but it behaves like a single gene

Question 13

define an allele

Answer 13

alternative form at a given locus

Question 14

define dominant

Answer 14

the allele that manifests itself regardless of the other allele that is present - indicated by an upper-case letter (e.g. A) - the trait that is manifest in a hybrid

Question 15

define recessive

Answer 15

an allele whose effect is “masked” when the dominant allele is present - all alleles at a locus must be recessive in order for the recessive allele to manifest itself - indicated by a lower-case letter (e.g. a)

Question 16

define homozygous

Answer 16

when both alleles at a given diploid locus
are the same – i.e. AA or aa

Question 17

define heterozygous

Answer 17

when there is one dominant and one
recessive allele present at a diploid locus– i.e. Aa

Question 18

define homozygote

Answer 18

an individual who is homozygous at the
locus in question

Question 19

define heterozygote

Answer 19

an individual who is heterozygous at the locus in question

Question 20

define hybrid

Answer 20

derived from two different parents

Question 21

define monohybrid

Answer 21

one hybrid locus

Question 22

define dihybrid

Answer 22

two hybrid loci

Question 23

define true-breeding

Answer 23

homozygous at the loci/locus in question

Question 24

define P

Answer 24

parental generation

Question 25

define F1

Answer 25

first filial generation - the offspring derived from the parental generation

Question 26

define F2

Answer 26

second filial generation - the offspring derived from the F1 generation

Question 27

define self

Answer 27

an inbreeding cross that involves individuals that are genetically identical (eg a plant with itself, or between full siblings derived from true breeding plants)

Question 28

Mendel's experiments - monohybrid cross

Answer 28

- green peas (yy) crossed with yellow peas (YY) - F1 all yellow (Yy) - self-fertilisation of F1 - F2 yellow:green = 3:1 - the reappearance of the recessive trait completely disproves 'blending' and uni parental inheritance

Question 29

how did Mendel infer the law of segregation (Mendel's First Law)?

Answer 29

F3 - diagram on slide 26

Question 30

define and explain the law of segregation (Mendel's First Law)

Answer 30

- two members of a gene pair segregate from each other into the gametes, so that one-half of the gametes carry one member of the pair and the other one-half of the gametes carry the other member of the pair - the alleles unite at random, one from each parent, at fertilisation

Question 31

Mendel's first law incorporates the fact that his results reflected

Answer 31

basic rules of probability

Question 32

define genotype

Answer 32

pair of alleles present in an individual

Question 33

define phenotype

Answer 33

observable characteristic of an organism

Question 34

give an example of how genotype and phenotype differed in Mendel's experiments

Answer 34

F2 generation phenotype ratio was 3:1 = yellow:green genotype ratio was 1:2:1 = YY:Yy:yy

Question 35

how can we discriminate between dominant homozygotes (eg YY) and heterozygotes (Yy)?

Answer 35

Test crosses reveal unknown genotypes: unknown genotype x homozygous recessive diagram on 34

Question 36

Mendel's experiments: dihybrid crosses

Answer 36

- crossed YYRR (yellow and round) with yyrr (green and wrinkled) - F1 were all identical (YyRr) - in F2, there were 4 different phenotypic combinations, including ones that weren't originally present in the parents. - 16 possible allelic combinations, 9 unique genotypes, 4 different phenotypes - this suggested that there had been a shuffling of alleles, proposed in the law of independent assortment

Question 37

Mendel's second law - Law of independent assortment

Answer 37

- during gamete formation, the segregation of alleles at one locus is independent of the segregation of alleles at another locus - results in predictable ratios of phenotypes in the F2 generation as shown by a Punnett square - follows basic laws of probability

Question 38

how can we calculate the number of possible allele combinations in gametes?

Answer 38

2^n n= number of gene loci where the organism has two different alleles

Question 39

use of product rule

Answer 39

Product Rule – "AND" Situations Use the product rule when you're calculating the probability of two or more independent events happening together.

Question 40

use of sum rule

Answer 40

Sum Rule – "OR" Situations Use the sum rule when calculating the probability of either of two mutually exclusive events occurring.

Question 41

Law of probability for multiple genes

Answer 41

loci assort independently - so we look at each locus independently to get the answer (eg on slide 43)

Question 42

summary of Mendel's 1865 paper

Answer 42

1. inheritance is particulate - not blending 2. there are two copies of each trait in a germ cell (before meiosis) 3. gametes contain one copy of the trait 4. alleles segregate randomly 5. alleles are dominant or recessive - thus the difference between genotype and phenotype 6. different traits assort independently

Question 43

issues with Mendel's laws

Answer 43

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

Question 44

how do we know that dominance is not always complete?

Answer 44

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

Question 45

incomplete dominance

Answer 45

- 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 46

codominance

Answer 46

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

Question 47

draw a table portraying a summary of dominance relationships

Question 48

give an example of incomplete dominance in plants

Answer 48

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 49

give an example of incomplete dominance in animals

Answer 49

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 50

give an example of incomplete dominance in humans

Answer 50

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 51

can a gene have more than two alleles?

Answer 51

- 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 52

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

Answer 52

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

Question 53

dominance relations are unique to

Answer 53

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

Question 54

dominance relations in the ABO blood group gene

Answer 54

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

Question 55

how many possible phenotypes are there for blood type?

Answer 55

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

Question 56

how is the ABO gene an example of codominant alleles?

Answer 56

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 57

lentil coat pattern alleles are an example of

Answer 57

codominant alleles

Question 58

describe the genetic mechanisms underlying lentil coat patterns

Answer 58

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 59

draw a table of blood type and antibodies in serum

Answer 59

O is universal donor

Question 60

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

Answer 60

AB is universal recipient

Question 61

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

Answer 61

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

Question 62

dominance series of agouti gene

Answer 62

A-: agouti atat: black/yellow aa: black ata: black/yellow A>at>a

Question 63

pleiotropy

Answer 63

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

Question 64

some alleles may cause lethality. what does this mean?

Answer 64

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 65

explain why lethality-causing alleles deviate from Mendelian ratios

Answer 65

- 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 66

King George 3rd's 'madness'

Answer 66

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 67

inheritance of coat colour in mice as an example of lethality

Answer 67

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 68

coat colour in mice shows the importance of avoiding

Answer 68

consanguineous mating

Question 69

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

Question 70

sickle cell anaemia

Answer 70

- 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 71

how do sickle cells confer resistance to malaria?

Answer 71

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

Question 72

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

Question 73

variable expressivity

Answer 73

a phenotype that varies in intensity

Question 74

example of variable expressivity

Answer 74

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

Question 75

incomplete penetrance

Answer 75

the phenotype is not always observed among individuals carrying the genotype

Question 76

example of incomplete penetrance

Answer 76

DD or Dd only result in 80% polydactyly

Question 77

opposite of variable expressivity

Answer 77

unvarying expressivity

Question 78

define penetrance

Answer 78

% of individuals with a genotype that express the phenotype

Question 79

why do penetrance and expressivity vary?

Answer 79

- 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 80

complete penetrance and unvarying expressivity

Question 81

incomplete penetrance and unvarying expressivity

Question 82

complete penetrance and variable expressivity

Question 83

incomplete penetrance and variable expressivity

Question 84

give an example of variable expressivity

Answer 84

coat spots/colour on dogs (slide 26)

Question 85

give an example of variable expressivity due to environmental modification

Answer 85

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 86

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

Answer 86

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

Question 87

complementation

Answer 87

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 88

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

Answer 88

recessive

Question 89

Astyanax mexicanus

Answer 89

- 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 90

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

Answer 90

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 91

allelic

Answer 91

alleles of the same gene

Question 92

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

Answer 92

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 93

how do we distinguish between complementation and allelism?

Answer 93

- 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 94

molecular vs phenotypic visibility of allelism

Answer 94

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 95

history of tomatoes and why they are good genetic models

Answer 95

- 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 96

purpose of testing for allelism

Answer 96

interested in finding genes responsible for a particular trait

Question 97

forward genetics experiment

Answer 97

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

Question 98

process of testing for allelism or complementation

Answer 98

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 99

if allelism is the case

Answer 99

- 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 100

if complementation is the case

Answer 100

- 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 101

complementation testing

Answer 101

- 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 102

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

Answer 102

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 103

give two examples of complementation in humans

Answer 103

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 104

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 104

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 105

recessive epistasis

Answer 105

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 106

epistasis

Answer 106

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 107

epistatic ratios allow a geneticist to hypothesise about

Answer 107

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

Question 108

upstream step

Answer 108

earlier in the pathway

Question 109

example of recessive epistasis in animals

Answer 109

slide 27

Question 110

example of recessive epistasis in humans

Answer 110

- 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 111

complementary gene action/reciprocal recessive epistasis

Answer 111

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 112

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

Answer 112

slide 31

Question 113

dominant epistasis 1

Answer 113

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 114

give an example of dominant epistasis 1 in plants

Answer 114

slide 33

Question 115

dominant epistasis 2

Answer 115

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 116

give an example of dominant epistasis 2 in chicken

Answer 116

slide 35

Question 117

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

Answer 117

yes.

Question 118

what did Walter Sutton discover?

Answer 118

studied great lubber grasshopper: - body cells contained 22 chromosomes and X & Y chromosomes - gametes contained 11 chromosomes and X or Y in equal numbers - after fertilisation, cells with XX were females and cells with XY were males

Question 119

anatomy of a chromosome

Answer 119

- metaphase chromosomes are classified by the position of the centromere: metacentric (if it is in the middle of the chromosome) or acrocentric (if located close to an end) - sister chromatids are held together by centromeres - homologous chromosomes are a pair of chromosomes—one from each parent—that have the same size, shape, and genes at the same locations, but may carry different versions (alleles) of those genes.

Question 120

draw metacentric and acrocentric chromosomes

Answer 120

slide 5

Question 121

key stages of mitosis

Answer 121

Replication: Interphase - cell grows and DNA is copied Prophase – Chromosomes condense, spindle forms Segregation: Metaphase – Chromosomes line up in the middle Anaphase – Chromatids are pulled apart Telophase – New nuclei form Cytokinesis – Cell splits in two genetically identical 2n daughter cells

Question 122

key stages of meiosis

Answer 122

Interphase – DNA is copied Prophase I – Homologous chromosomes pair up and cross over Metaphase I – Pairs line up in the middle Anaphase I – Homologous chromosomes separate Telophase I – Two nuclei form Prophase II – New spindles form in each cell Metaphase II – Chromosomes line up in the middle Anaphase II – Chromatids are pulled apart Telophase II – Four nuclei form Cytokinesis – Four haploid cells result

Question 123

key differences between mitosis and meiosis

Answer 123

Number of divisions: Mitosis = 1 Meiosis = 2 Number of daughter cells: Mitosis = 2 (diploid) Meiosis = 4 (haploid) Genetic similarity: Mitosis = Identical to parent Meiosis = Genetically different (variation) Purpose: Mitosis = Growth, repair, asexual reproduction Meiosis = Sexual reproduction (gametes) Homologous chromosomes: Mitosis = Do not pair Meiosis = Pair and crossover in Prophase I

Question 124

how was movement of chromosomes during mitosis and meiosis understood ?

Answer 124

microscopy provided a means to follow movement of chromosomes during cell division

Question 125

gamete

Answer 125

contains one-half the number of chromosomes as the zygote

Question 126

haploid

Answer 126

cells that carry only a single chromosome set

Question 127

diploid

Answer 127

cells that carry two matching chromosome sets

Question 128

n

Answer 128

the number of chromosomes in a haploid cell

Question 129

2n

Answer 129

the number of chromosomes in a diploid cell

Question 130

is chromosome number constant across species?

Answer 130

no, it varies from species to species but does not correlate with the size or complexity of the animal

Question 131

somatic cells

Answer 131

divide mitotically and make up the vast majority of an organism's tissues

Question 132

germ cells

Answer 132

specialised role in the production of gametes:

Question 133

process of creation of a diploid offspring

Answer 133

- germ cells arise during embryonic development in animals and floral development in plants - undergo meiosis to produce haploid gametes - gametes unite with gamete from opposite sex to produce diploid offspring

Question 134

karyotype

Answer 134

- produced by cutting micrograph images of stained chromosomes and arranging them in matched pairs - sex chromosomes and autosomes are arranged in homologous pairs

Question 135

autosomes

Answer 135

pairs of non-sex chromosomes

Question 136

sex chromosome

Answer 136

- provide basis for sex determination - one sex has matching pair, other sex has non-matching sex chromosomes - variation in sex determination between species

Question 137

mammal and drosophila sex chromosomes

Answer 137

female: XX male: XY

Question 138

some grasshoppers sex chromosomes

Answer 138

female: XX male: XO

Question 139

fish, birds, moths sex chromosomes

Answer 139

female: ZW male: ZZ

Question 140

sex determination in humans

Answer 140

children receive only one X chromosome from mother but either X or Y from father

Question 141

X chromosomes in females

Answer 141

females typically have two X chromosomes that are genetically identical

Question 142

how are chromosome behaviour and inheritance related?

Answer 142

chromosomes determine characteristics of organism (eg its sex); therefore, basis of inheritance must reside there

Question 143

mitosis ensures that

Answer 143

every cell in an organism carries the same set of chromosomes

Question 144

meiosis ensures that

Answer 144

one member of each chromosome pair is distributed to gamete cells

Question 145

gametogenesis

Answer 145

the process by which germ cells differentiate into gametes

Question 146

6 links between chromosome and gene behaviour

Answer 146

- each cell contains 2 copies of each chromosome; each cell contains 2 copies of each gene - chromosome complements appear unchanged during transmission from parent to offspring; genes appear unchanged during transmission from parent to offspring - homologous chromosomes pair and then separate to different gametes; alternative alleles segregate to different gametes - maternal and paternal copies of chromosome pairs separate without regard to the assortment of other homologous chromosome pairs; alternative alleles of unrelated genes assort independently - at fertilisation an egg's set of chromosomes unite with randomly encountered sperm's chromosomes; alleles obtained from one parent unite at random with those of another parent ; alleles obtained from one parent unite at random with those of another parent - in all cells derived from a fertilised egg, one half of chromosomes are of maternal origin, and half are paternal; in all cells derived from a fertilised gamete, one half of genes are of maternal origin, and half are paternal

Question 147

Thomas hunt morganatic

Answer 147

- started using a new genetic model: drosophila melanogaster, the common fruitfully - in 1910, morgan discovered a white-eyed male among his true-breeding stocks of red-eyed flies (first drosophila mutation identified)

Question 148

advantages of drosophila as a model organism

Answer 148

- small size - short generation time of 10 days at room temp - each female lays 400-500 eggs - easy to culture in laboratory - small genome - large chromosomes - many mutations available

Question 149

draw a table describing how sex determination in humans differs from drosophila

Question 150

nomenclature for drosophila genetics

Answer 150

wild type allele: allele that is found in high frequency in a population (greater than or equal to 1%) is denoted with a + mutant allele: allele that is found in low frequency (less than 1%): denoted with no symbol recessive mutation: gene symbol is in lower case dominant mutation: gene symbol is in upper case

Question 151

examples of notations for drosophila

Answer 151

- Cy, Sb, D are dominant mutations - vg, v, y, e are recessive mutations - vg+ - wild type allele for vestigial gene locus - Cy+ - wild type allele for curly gene locus

Question 152

eye colour in drosophila

Answer 152

- flies with red eyes carry the wild type allele, w+ - any variation in eye colour carry a mutant allele (eg white eye colour), w

Question 153

how was X-linkage of eye colour in drosophila demonstrated?

Answer 153

1. observed true-breeding sex ratios (1/2 male, 1/2 female in both F1 and F2) 2. P cross: crossed a white-eyed male (w/Y) to a red-eyed female (w+/w+). all F1 offspring had red eyes, suggesting the white-eyed trait was recessive 3. F1 cross: crossed w+/w female to w+/Y male. all female offspring were red-eyed; male were white and red-eyed. thus, morganatic proposed that the eye colour gene is on the X chromosome.

Question 154

sex linkage

Answer 154

genes for specific traits are carried on sex chromosomes

Question 155

hemizygous

Answer 155

means having only one copy of a gene instead of the usual two (eg in males with X-linked genes)

Question 156

what was Bridges' hypothesis and how did it arise?

Answer 156

X chromosomes were not segregating properly in meiosis, leading to 1/2000 females being white-eyed and 1/2000 males being red-eyed during a w/w x w+/Y cross

Question 157

how was Bridges' hypothesis proved?

Answer 157

he did large enough experiments to observe rare meiotic events he called non-disjunction.

Question 158

draw 3 diagrams: - normal X chromosome segregation - nondisjunction in meiosis I - nondisjunction in meiosis II

Answer 158

slide 34

Question 159

how did nondisjunction lead to unexpected phenotypes in drosophila?

Answer 159

males receive one X chromosome from father: red eyes females receive two X chromosomes from mother: white eyes

Question 160

reciprocal crosses done to confirm X linkage

Answer 160

reciprocal cross of w/w females with w+/Y males. F1 was red-eyed females and white-eyed males only. F2 cross of w+/w females with w/Y males resulted in half offspring having white eyes, half having red eyes. females 1:1 red: white, males 1:1 red:white.

Question 161

what was the final evidence that phenotypes are associated with chromosomes and thus that genes are carried on chromosomes?

Answer 161

- Bridges crossed XXY females (white eyes) to the normal XY males (red eyes) in order to confirm his theory - unusual inheritance patterns correlate with aneuploidy

Question 162

aneuploidy

Answer 162

abnormal number of chromosomes

Question 163

X-linked recessive traits exhibit 6 characteristics seen in pedigrees

Answer 163

- Trait appears in more males than females. - Mutation and trait never pass from father to son. - Affected male does pass X-linked mutation to all daughters, who are then unaffected carriers. - Trait often skips a generation. - Trait only appears in successive generations if sister of an affected male is a carrier. If so, her sons have a 50% chance of showing the trait. - All sons of affected female show trait and all daughters of affected female are carriers.

Question 164

example of X-linked recessive trait in humans

Answer 164

haemophilia A

Question 165

X-linked dominant traits exhibit 4 characteristics seen in pedigrees

Answer 165

- Trait appears in more females than males. - Sons and daughters of an affected heterozygous female have a 50% chance of showing the trait. - Trait is seen every generation. - All daughters but no sons of affected male show trait.

Question 166

example of X-linked dominant trait in humans

Answer 166

hypophosphatemia

Question 167

Y-linked traits exhibit 3 characteristics seen in pedigrees

Answer 167

- Trait appears only in males. - All sons but no daughters of affected male show trait. - Females do not show and cannot transmit trait.

Question 168

what unusual observations did Bateson and Punnett make?

Answer 168

when crossing purple flowers, long pollen (PPLL) with red flowers, round pollen (ppll) they found more parental-type combinations and fewer recombinants than expected. however, according to Mendel’s law of independent assortment, they expected a 9:3:3:1 ratio in the F2 generation.

Question 169

what unusual observations did Morgan make?

Answer 169

crossed red eyed, full size wing (pr+vg+/pr+vg+) with purple eye, vestigial wing (pr vg/pr vg) again, parental combinations appeared more often than recombinant ones and recombinant types were less frequent than expected by chance.

Question 170

what did Frans Janssens observe in 1909? what did Morgan suggest relating to this?

Answer 170

chiasmata, regions in which nonsister chromatids of homologous chromosomes cross over each other. Morgan suggested these were sites of chromosome breakage and exchange resulting in genetic recombination

Question 171

cytogenetics

Answer 171

The study of chromosomes inside cells, especially during cell division.

Question 172

crossovers

Answer 172

- physical exchanges among nonsister chromatids; visualised cytologically as a chiasma (plural = chiasmata) - typically, several crossing-over events occur within each bivalent or tetrad in each meiosis

Question 173

function of chiasmata

Answer 173

physically hold homologous chromosomes together and assure proper segregation at anaphase I

Question 174

Morgan's first prediction and second prediction relating to crossing over

Answer 174

First: - Crossing over occurs during meiosis between homologous chromosomes, allowing genes to be exchanged. - This explains how linked genes can sometimes produce recombinant offspring Second: - The frequency of crossing over between two genes is proportional to the distance between them on the chromosome. - Genes closer together have less chance of crossover (more likely inherited together).

Question 175

Mendel's fruit fly test cross progeny ratios

Answer 175

>50% of progeny have parental type (1/4 one, 1/4 other) <50% have recombinant phenotype

Question 176

genetic recombination depends on

Answer 176

the reciprocal exchange of parts between maternal and paternal chromosomes

Question 177

what did McClintock and Creighton observe?

Answer 177

- They studied corn (maize) chromosomes with visible physical markers (like a knob on one chromosome end and a translocation on the other). - They tracked the inheritance of these physical chromosome markers alongside genetic traits. - this provided visual confirmation that chromosomes cross over - correlation between genetic crossover and chromosomal crossover - this was verified in drosophila by Stern

Question 178

Meiosis contributes to genetic diversity in 2 ways

Answer 178

- independent assortment of non homologous chromosomes creates different combinations of alleles among chromosomes - crossing over between non sister homologous chromatids creates different combinations of alleles within each locus

Question 179

when does recombination take place?

Answer 179

at the four-chromatid (four-strand) stage of Meiosis I (prophase I)

Question 180

5 stages of crossing over

Answer 180

1. leptotene: thread-like chromosomes begin to condense, becoming visible as discrete structures, although the sister chromatids cannot yet be distinguished 2. zygotene: chromosomes are clearly visible and begin pairing with homologous chromosomes along the synaptonemal complex to form a bivalent, or tetrad 3. pachytene: the homologs synapse fully, recombination nodules appear along the synaptonemal complex 4. diplotene: the bivalent pulls apart slightly, but homologous chromosomes remain connected due to recombination at crossover sites (chiasmata) 5. diakinesis: the bivalent condenses further

Question 181

synaptonemal complex

Answer 181

zipper-like elaborate protein structure that aligns chromosomes base pair by base pair

Question 182

terminalization

Answer 182

process where the chiasmata move from the middle of the homologous chromosomes toward the ends (telomeres) as meiosis progresses, especially during diplotene and diakinesis stages

Question 183

what happens after terminalization?

Answer 183

anaphase I

Question 184

Holliday's model for mechanism of recombination

Answer 184

1. Homologues physically break, exchange parts, and rejoin 2. Breakage and repair create reciprocal products of recombination 3. Recombination events can occur anywhere along the length of a DNA molecule, but at some locations with a higher frequency than others 4. The exchange is precise - no gain or loss of nucleotide pairs occurs– thus preventing mutation from occurring 5. Gene conversion - where small segments of information from one homologous chromosome transfers to the next - may result in unequal yield of the two alleles

Question 185

draw a table showing the meiotic products based on crossover between genes

Answer 185

slide 27

Question 186

genetic recombination

Answer 186

mixing of genes during gametogenesis produces gametes with combinations of genes that are different from the combinations received from parents

Question 187

unlinked vs linked genes

Answer 187

- genes on non homologous chromosomes (unlinked genes) assort independently - genes on the same chromosome co-segregate

Question 188

crossovers result in recombination between

Answer 188

linked genes

Question 189

crossover frequency is a function of

Answer 189

the distance between two loci

Question 190

can crossover ever occur when genes are completely linked?

Answer 190

no; the genes are too close

Question 191

recombination frequency can never exceed

Answer 191

50% (ie more recombinant types than parental types)

Question 192

single crossover vs double crossover

Answer 192

single: parental and recombinant double: all parental

Question 193

how do you test for linked vs unlinked genes?

Answer 193

test cross to distinguish between linked and unlinked genes, you'd typically cross a heterozygous individual with a homozygous recessive individual for the traits being studied. 2 genes unliked = 1:1 between parental genotypes and recombinant genotypes 2 genes linked = more parental genotypes than recombinant genotypes

Question 194

define a discontinuous trait and give an example

Answer 194

clear-cut, 'either-or' phenotypes between alternative alleles eg. all of the traits Mendel studied in peas

Question 195

how does the phenotype vary in incomplete dominance?

Answer 195

the phenotype varies continuously with levels of protein function/the amount of functional gene product

Question 196

molecular mechanisms of incomplete dominance in snapdragon colour

Answer 196

A1: functional enzyme A2: nonfunctional enzyme A1A1: red (100% pigment production) A1A2: pink (50% pigment production) A2:A2: white (0% pigment production)

Question 197

how is familial hypercholesteremia an example of incomplete dominance?

Answer 197

the heterozygous phenotype (250-500mg/dl) is distinct from and intermediate compared to either homozygous phenotype (<250mg/dl and >500mg/dl)

Question 198

qualitative trait: - examples - mode of inheritance - environmental effects

Answer 198

- blood and serum types, enzyme defects - simple Mendelian (monogene) - little environmental effect

Question 199

quantitative trait - examples - mode of inheritance - environmental effects

Answer 199

- stature height, intelligence, milk yield - complex (polygene) - moderate to great environmental effect

Question 200

threshold trait - examples - mode of inheritance - environmental effects

Answer 200

- hare lib, many diseases - complex (polygene) - moderate to great environmental effect

Question 201

what kind of distribution does continuous variation typically have?

Answer 201

a normal distribution, which is bell-shaped

Question 202

what is the Mendelian explanation of continuous variation?

Answer 202

alleles are incompletely dominant and have additive effects. the more genes or alleles, the more possible phenotypic classes, the greater the similarity to continuous variation

Question 203

what interaction results in the normal distribution of a quantitative trait?

Answer 203

genetic and environmental influences

Question 204

draw 3 graphs for no of individuals vs trait value: - two genes, two incompletely dominant alleles - environmental influences - normal distribution

Question 205

what could be the result of more than two alleles of the same gene?

Answer 205

additional variation might arise

Question 206

additive alleles

Answer 206

contribute to traits in a cumulative manner. the more of a particular allele an individual has, the stronger the expression of that trait

Question 207

give an example of the impact of additive alleles on human traits

Answer 207

- a handful of ultra rare inherited mutations likely shave years off a person's life - each of these DNA variants can reduce lifespan by as much as 6 months - and different combinations dictate how early age-related diseases such as cancer, diabetes, and dementia will develop - thus, each variant is an additive allele

Question 208

define continuous traits and give examples in humans

Answer 208

are determined by segregating alleles of many genes that interact together and with the environment eg height, weight, skin colour

Question 209

what is another name for continuous traits?

Answer 209

quantitative traits

Question 210

continuous traits are usually

Answer 210

polygenic

Question 211

three categories of quantitative traits

Answer 211

meristic (counting traits): takes on a range of discrete values. these traits are quantitative, but restricted to certain discrete values (eg salamander spots) continuous traits: takes on a potentially infinite number of states or values over a continuous range (eg height) threshold trait: individuals who have a certain number of risk factors will exceed a threshold and develop the disease.

Question 212

do threshold traits follow Mendelian rules?

Answer 212

no, they do not follow simple Mendelian rules or produce Mendelian ratios in pedigrees

Question 213

give an example of environmental modification of certain mutations

Answer 213

siamese cats

Question 214

quantitative trait locus (QTL)

Answer 214

region of the genome that correlates with the quantitative trait and may contain the genes affecting the quantitative trait

Question 215

how can quantitative traits be described by a frequency distribution?

Answer 215

frequency distributions associated with each genotype at the QTL overlap. we cannot determine genotype by simply looking at an individual's phenotype as we can with genes that segregate in Mendelian ratios

Question 216

how does our predictive power of genotype from phenotype vary with trait value? draw a graph

Answer 216

at either end (low or high trait value) we can guess the genotype from the phenotype. however, at intermediate trait values, this is very hard

Question 217

phenotype =

Answer 217

genotype + environment

Question 218

how can we determine how much variation is attributable to genetic or environmental variation?

Answer 218

we can separate the genetic effects from the environmental effects by quantifying one variable, while controlling the other

Question 219

draw a graph of stem length vs number of plants, and label the mean and variation

Question 220

equation for mean

Question 221

equation for variance

Question 222

Ve

Answer 222

environmental variance - the portion of phenotypic variation in a population that is due to environmental factors, rather than genetic factors

Question 223

Vg

Answer 223

genetic variance - a measure of the variation in a trait due to differences in genotype within a population

Question 224

Vp =

Answer 224

Vg + Ve

Question 225

Broad sense heritability of a trait

Answer 225

the extent of phenotypic variation that is attributable to genetic variation H^2 = Vg/Vp

Question 226

describe what different values of H^2 could mean

Answer 226

H^2 = 1 - all the phenotypic variation is attributable to genetic variation H^2 = 0 - all the phenotypic variation is attributable to environmental effects

Question 227

how and why is the heritability of a trait defined?

Answer 227

- heritability of a trait is always defined for a specific population or specific family in a specific set of environmental conditions - this is because the amounts of genetic, environmental, and phenotypic variation may differ among traits, families, populations and among different environments

Question 228

what does H^2 tell us? what does H^2 NOT tell us?

Answer 228

Tells Us: If H^2 is high, the phenotype of an individual is likely to be attributable to its genotype IN THAT FAMILY Does not tell us: 1. What phenotype an individual will have based on their parents' phenotypes. Even if H^2 is high, an individual's precise phenotype cannot be predicted based on its parents' phenotypes (parents pass on their alleles, not their genotype) 2. What is going on in other families. H^2 is family specific and varies among different families, populations, or environments

Question 229

why is H^2 not predictive?

Answer 229

Vp = Vg + Ve however, Vg = Va + Vd + Vi where - Va is variation due to additive effects - Vd is variation due to dominance effects - Vi is variation due to epistatic effects

Question 230

Vd

Answer 230

dominance variance, which is the portion of genetic variance attributable to interactions between alleles at the same locus

Question 231

is Vi predictive?

Answer 231

epistatic interaction variation is not transmitted from parents to offspring -> new genotypes and thus new epistatic relationships are formed with each generation

Question 232

if a trait is due to additive effects, is it predictive?

Answer 232

yes

Question 233

narrow-sense heritability

Answer 233

the extent of phenotypic variation that is attributable to additive genetic variation

Question 234

describe different h^2 values and what they can mean

Answer 234

if all the phenotypic variation is attributable to additive variation, h^2 = 1 (the maximum it can be) if all the phenotypic variation is attributable to other genetic and environmental effects, h^2 approaches 0

Question 235

h^2 =

Answer 235

Va/Vp

Question 236

use bill depth in Darwin's finches as an example of narrow sense heritability

Answer 236

~ 18% of variation is attributed to the environment and or dominant or epistatic genetic variation slope = 0.82 ~ 82% of variation is attributed to additive genetic variation

Question 237

what does h^2 tell us vs not tell us?

Answer 237

tells us: if h^2 is high, the phenotype of an individual is predictable based on the phenotype of its parent in that family does not tell us: what is happening in other families

Question 238

how can twins be used to study heritability of polygenic traits?

Answer 238

1. monozygotic twins: single ovulated egg fertilised by one sperm, then the embryo splits into two. 100% of alleles are shared, so we can study the effect of different environments on the same genotype 2. dizygotic twins: two ovulated eggs fertilised by different sperm, so 50% of alleles are shared, so we can study the effect of different genotypes on the same environment

Question 239

define a mutation

Answer 239

change genes from one allelic form to another, sometimes leading to the creation of entirely new alleles

Question 240

when do genes mutate?

Answer 240

genes mutate randomly, at any time and in any cell of an organism

Question 241

how often do genes mutate?

Answer 241

very rarely; on average 1.2x10^-8 mutations/gene/gamete in humans

Question 242

what causes a gene to mutate?

Answer 242

spontaneous: - arise in absence of known mutagen (polymerase errors, reactive oxygen species etc) - provide 'background rate' of mutation induced (by geneticist -> mutagenesis) - action of mutagen alters nucleotide sequence

Question 243

what types of mutations can and can't be passed onto progeny?

Answer 243

only mutations in germline cells can be transmitted to progeny; somatic mutations cannot be transmitted

Question 244

inherited mutations appear as ---- in populations

Answer 244

alleles

Question 245

state 3 observations of mutation rates

Answer 245

- mutations affect phenotype rarely - different genes mutate at different rates (mutation rates range from less than 10^-9 to more than 10^-3/gene/gamete) - mutation rate can increase after exposure to a mutagen (eg UV light, certain chemicals)

Question 246

define a substitution

Answer 246

a base is replaced by one of the other 3 bases

Question 247

indels

Answer 247

deletions - block of one or more nucleotide (base) pairs is lost insertion - block of one or more nucleotide (base pairs is added)

Question 248

what are the two types of base substitutions?

Answer 248

transition: purine to purine (A<->G) or pyrimidine to pyrimidine (C<->T) transversioin: purine to pyrimidine or pyrimidine to purine

Question 249

purines

Answer 249

guanine, adenine

Question 250

pyrimidines

Answer 250

thymine, cytosine

Question 251

why do we study mutations?

Answer 251

- they act as markers for genes - mutations can disrupt gene function. this allows for the study of how the wild-type gene works

Question 252

wild-type allele

Answer 252

the form found in nature (or in a standard laboratory stock); an allele whose frequency is 1% or more of the population

Question 253

mutant allele

Answer 253

the form that has changed due to a mutation; an allele whose frequency is less than 1% of the population

Question 254

forward mutation

Answer 254

changes wild-type allele to a different allele

Question 255

reverse mutation (reversion)

Answer 255

causes novel mutation to revert back to wild-type allele

Question 256

which is higher - rate of forward or rate of reverse mutation

Answer 256

rate of forward mutation is almost always higher than rate of reverse mutation (except TEs)

Question 257

depurination

Answer 257

the hydrolysis of a purine base from the deoxyribose-phosphate backbone, leading to an apurinic site

Question 258

how often does depurination occur?

Answer 258

100 times/hour in every human cell

Question 259

deamination

Answer 259

the removal of an amino group from a cytosine, leading to the conversion of cytosine to uracil

Question 260

how is deamination fixed?

Answer 260

by uracil-DNA glycosylase - most of the time, it is easy for cells to recognise deamination as uracil is only meant to be in RNA, not DNA

Question 261

how does deamination affect DNA strands resulting from replication?

Answer 261

- after replication, one of the strands will be normal (CG) and the other will be mutant (UA) as adenine base pairs with uracil - after another round of replication, one of the strands will be (TA) and the other will be (UA) overall, there is a C-G to T-A transition mutation

Question 262

give examples of radiation that may cause mutations

Answer 262

naturally occurring radiation such as cosmic rays and x rays often lead to mutations like deletions

Question 263

what kind of mutation does UV light cause and how?

Answer 263

- UV light (especially UV-B and UV-C) primarily causes pyrimidine dimers - induces covalent bonds between adjacent pyrimidines (especially thymine-thymine dimers, but also C-T and C-C).

Question 264

describe how oxidation leads to mutation

Answer 264

- oxidative damage can occur to any of the 4 base pairs - ROS oxidize guanine into 8-oxoG. 8-oxoG mispairs with adenine during replication. This causes a G:C → T:A transversion in the next round of replication.

Question 265

describe how DNA polymerases may lead to mutation

Answer 265

- DNA polymerases may lead to DNA replication mistakes - this is caused by the incorporation of an incorrect during replication

Question 266

how often do DNA replication mistakes occur?

Answer 266

DNA polymerase has very high fidelity, so such errors are exceedingly rare

Question 267

where do indel mutations tend to occur?

Answer 267

in regions of repeated bases during replication or crossing over in meiosis

Question 268

trinucleotide repeat expansion

Answer 268

DNA polymerase can slip or misalign on the template strand, forming a loop of extra repeats on the new strand, leading to expansion

Question 269

trinucleotide repeat contraction

Answer 269

DNA polymerase can slip or misalign on the template strand, forming a loop of extra repeats on the template strand, leading to contraction

Question 270

give examples of diseases caused by intel mutations of regions with repeated bases

Answer 270

Fragile X-syndrome, Huntington and other disorders of the nervous system

Question 271

define genetic code

Answer 271

- dictionary used to translate nucleic acids to a amino acids - codon language - redundant (multiple codons per amino acid)

Question 272

why is redundancy of the genetic code important?

Answer 272

this protects against the negative impacts of mutations

Question 273

silent (synonymous) mutation

Answer 273

altered codon resulting from the mutation specifies the same amino acid

Question 274

missense mutation

Answer 274

altered codon resulting from the mutation specifies a different amino acid

Question 275

southern blot

Answer 275

identifies specific DNA sequences

Question 276

northern blot

Answer 276

identifies (m)RNA sequences

Question 277

western blot

Answer 277

identifies protein sequences

Question 278

two types of missense mutations

Answer 278

conservative: - substitutes chemically similar amino acid - less likely to alter function or structure of protein non-conservative: - substitutes chemically different amino acid - more likely to alter function or structure of protein

Question 279

nonsense mutation

Answer 279

introduction of a (early) stop codon (TAG, TAA, TGA)

Question 280

frameshift mutation

Answer 280

- the insertion or deletion of nucleotides in a DNA sequence not in multiples of three - shifts the reading frame used during translation, drastically altering the resulting protein

Question 281

intragenic suppressor mutation

Answer 281

a second mutation that occurs within the same gene as a previous mutation and restores, at least partially, the original function that was lost or disrupted by the first mutation

Question 282

two types of mutations outside the coding sequence

Answer 282

- mutations in promoter or termination signal sites - splice donor/acceptor site mutations

Question 283

splice donor/acceptor site mutations

Answer 283

- disrupts splice donor/acceptor site, resulting in incorrect retention/excision of intron - often leads to large additions or deletions that may cause frameshift

Question 284

loss-of-function mutation

Answer 284

result in reduced or abolished protein activity

Question 285

what is the typical inheritance mode of loss of function mutations?

Answer 285

loss-of-function mutations are usually recessive

Question 286

two types of loss-of-function mutations

Answer 286

- null (amorphic) mutations - completely block function of gene product (eg deletion of an entire gene) - hypomorphic mutations - gene product has weak, but detectable, activity

Question 287

haplosufficiency

Answer 287

- when one WT allele reaches threshold for the WT phenotype, the WT allele is haplosufficient - even with one mutant allele, we still see the WT phenotype - recessive mutations

Question 288

haploinsufficiency

Answer 288

- when one WT allele does not reach the threshold for the WT phenotype, the WT allele is haploinsufficient - heterozygotes are affected - dominant mutations

Question 289

give an example of haploinsufficiency

Answer 289

polydactyly - phenotype is seen in individuals with only one mutant copy

Question 290

incomplete dominance

Answer 290

phenotype varies with the amount of functional gene product

Question 291

gain of function mutations

Answer 291

enhance a function or confer a new activity

Question 292

what mode of inheritance do gain of function mutations typically have?

Answer 292

they are typically dominant

Question 293

two types of gain-of function mutations

Answer 293

hypermorphic mutations: - generate excessive gene product or more potent gene product neomorphic mutations: - generate gene product with new functions or ectopically expressed at inappropriate time or place, generating a novel phenotype

Question 294

give an example of a hypermorphic mutation

Answer 294

achondroplasia - caused by a hypermorphic allele of the FGFR3 gene, which leads to increased receptor activity. - this overactive FGFR3 inhibits bone growth, resulting in the characteristic short stature.

Question 295

give an example of a neomorphic allele

Answer 295

mutation in Antennapedia gene of drosophila causes ectopic expression of a leg-determining gene in structures that normally produce antennae

Question 296

antimorphic/dominant negative mutations

Answer 296

- usually occur in genes that encode multimeric proteins - produce a mutant gene product that interferes with the function of the normal (wild-type) protein

Question 297

How did Garrod use mutations to understand gene function in phenylketonuria (PKU)?

Answer 297

- proposed that genes control metabolism by encoding specific enzymes. - In PKU, a mutation in the gene for phenylalanine hydroxylase leads to a loss of enzyme function, causing a buildup of phenylalanine. - This showed that mutations can block metabolic pathways, linking gene defects to biochemical function

Question 298

compare a normal pathway to alkaptonuria

Answer 298

normal pathway: phenylalanine -> tyrosine -> p-hydroxyphenylpyruvate -> homogentisic aid (HA) -> maleylacetoacetic acid -> CO + H2O in alkaptonuria: - HA oxidase nonfunctional - HA accumulates (toxic) - turns urine black in air - pathway stops

Question 299

how can we analyse biosynthetic pathways?

Answer 299

- compounds that are used latest in the pathway will support the growth of the most mutants - compounds that are used earliest in the pathway will support the growth of the fewest mutants

Question 300

What provides evidence for the importance of epigenetics?

Answer 300

genotype =/= phenotype - monozygotic twins are genotypical identical but not always phenotypically identical, and these differences can't always be explained by environment - mice with genotype A^vy/a genotype are also genetically identical, but some have brown fur and some have yellow fur

Question 301

define epigenetic

Answer 301

the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence

Question 302

state the 4 molecular mechanisms underlying epigenetics

Answer 302

1. DNA methylation on CpG islands 2. covalent modification of histone tails 3. noncovalent modification of histones 4. non-coding RNAs

Question 303

DNA methylation on CpG islands

Answer 303

CpG = Cytosine-phosphate-guanine nucleotides - some regions have many CpG islands, in which cytosine may be either methylated or unmethylated - typically, unmethylated promoters enable gene expression - typically, methylated promoters result in heterochromatin, repressing gene expression - the effects of methylation depend on the region; sometimes DNAm leads to silencing, sometimes it leads to increased expression

Question 304

covalent modification of histone tails

Answer 304

- acetylation: loosens chromatin by neutralizing lysine charges, promoting gene expression - methylation: can activate or repress gene expression, depending on the site and number of methyl groups. - ubiquitination: tags histones for degradation or signals chromatin remodeling, affecting transcriptional activity

Question 305

non-covalent modification of histones

Answer 305

reposition nucleosomes to make DNA more or less accessible.

Question 306

non-coding RNAs

Answer 306

Transcriptional Silencing: Small RNAs (like siRNAs) guide chromatin modifiers to DNA, causing heterochromatin formation and blocking transcription.

Question 307

how does chromatin structure affect transcription?

Answer 307

- promoters can be hidden when wrapped in nucleosomes, leading to lowered gene expression - chromatin remodelling complexes can expose gene promoters, allowing RNA polymerase to bind - nucleosomes in heterochromatin can be tightly packed, generating silenced heterochromatin

Question 308

epigenetic changes causing coat colour differences can be influenced by

Answer 308

the environment

Question 309

regulation of gene expression in A^vy/a mice

Answer 309

- the agouti gene is normally expressed in a regulated pattern, giving banded hairs (black-yellow-black) and brown/gray fur. - the Aᵛʸ allele contains an IAP (Intracisternal A Particle) retrotransposon upstream of the Agouti gene. - the IAP has a promoter that can drive ectopic (abnormal) Agouti expression. - Unmethylated IAP → promoter is active → overexpression of Agouti → yellow coat. - Methylated IAP → promoter silenced → Agouti expressed normally (or not at all) → brown or mottled coat.

Question 310

define a metastable epiallele

Answer 310

an allele whose expression is not fixed but can vary in a stable way between cells or individuals due to epigenetic states established early in development.

Question 311

how is A^vy an example of a metastable epiallele?

Answer 311

its expression is controlled by DNA methylation at a retrotransposon promoter, leading to variable, heritable gene expression without DNA sequence changes.

Question 312

what two main points were derived from experiments involving agouti mice?

Answer 312

1. Maternal diet can directly affect the epigenetic regulation of genes in offspring. 2. These changes can be stable enough to affect not just the immediate offspring, but also subsequent generations.

Question 313

How was the idea that maternal diet can directly affect the epigenetic regulation of genes in offspring understood?

Answer 313

- When pregnant mothers were fed a diet rich in methyl donors, their offspring showed a higher proportion of the pseudoagouti phenotype (brown fur). - This was because methylation silenced the Agouti gene, preventing ectopic expression and resulting in darker coat color. - When mothers were fed a normal diet, their offspring showed more of the yellow or mottled phenotypes. - This was due to lower methylation of the Agouti gene, allowing it to be expressed and leading to lighter coat color.

Question 314

How was the idea of intergenerational epigenetic inheritance understood?

Answer 314

- F0 mothers were supplemented with methyl donors during pregnancy. - Her F1 offspring showed increased methylation at the Agouti locus. - The F2 generation also exhibited more pseudoagouti phenotypes, despite not being directly exposed to the diet. - This suggested that the epigenetic marks were inherited through the germline. - F0 mothers were supplemented with no methyl supplementation. - the F1 and F2 offspring showed more yellow or mottled phenotypes, indicating low methylation.

Question 315

how is epigenetic required for normal development?

Answer 315

specific functions of different cell types are generated through differential gene regulation

Question 316

explain the randomness of X-chromosome inactivation and its consequences

Answer 316

- random X-chromosome inactivation in females occurs early during development for dosage compensation - these X-chromosomes are reactivated in germ cells - inactivation of the paternal/maternal X chromosome is random but persists in the subsequent cells produced - this means that females express X^m in some cells and X^p in others, leading to clonal patches

Question 317

give an example of X-chromosome inactivation and its phenotypic consequences in animals

Answer 317

in the calico cat, X-inactivation leads to a mosaic of fur colours

Question 318

mechanism of X-chromosome inactivation

Answer 318

- process begins at the X-inactivation centre (XIC), which activates the gene Xist. - Xist makes a long non-coding RNA (lncRNA) that spreads across the X chromosome, coating it and starting the silencing process. - Hypoacetylation of a Lys of histones (H3/H4), methylation of histone H3 and underlying DNA shut down gene expression - the inactive X becomes tightly packed into a structure called a Barr body. - most genes on this X are turned off, but a few, called escapees, remain active.

Question 319

how does histone acetylation lead to more loosely packed DNA?

Answer 319

- histone tail usually positively charged, DNA negatively charged - when the tail is acetylated, the charge is neutralised and DNA becomes more loosely packed

Question 320

Hypoacetylation vs Hyperacetylation

Answer 320

Hypoacetylation = regions that are silenced Hyperacetylation = transcriptionally active regions

Question 321

gene therapy approach for Down syndrome

Answer 321

autosome + one copy of Xist -> autosome becomes a heterochromatic Barr body thus, we could add Xist to one of the 3 copies of chromosome 21 in children with Down syndrome

Question 322

what is a synonym for parental imprinting?

Answer 322

genomic imprinting

Question 323

how does parental imprinting come about?

Answer 323

it results from transcriptional silencing

Question 324

define parental imprinting

Answer 324

when the expression of a gene depends upon its parental source (ie whether it is inherited from the maternal or paternal side)

Question 325

imprinted =

Answer 325

silenced

Question 326

paternally imprinted gene

Answer 326

- paternally silenced - only the maternal allele is expressed

Question 327

maternally imprinted gene

Answer 327

- maternally silenced - only the paternal allele is expressed

Question 328

how are imprinted genes usually modified?

Answer 328

- methylated by special methylases - demethylated by demethylases

Question 329

how is epigenetic state maintained across cell generations? draw a diagram

Answer 329

through the action of DNA methyltransferases, slide 22

Question 330

define silencing

Answer 330

long term repression through DNA methylation

Question 331

explain the resetting of genomic imprints during meiosis

Answer 331

- in the early primordial germ cells, existing methylation marks are removed. - later in gametogenesis, new methylation marks are added. - female places maternal imprints on all eggs - male places paternal imprints on all sperm

Question 332

draw the model for the imprinting of the IGF2 and H19 genes

Question 333

describe the model for the imprinting of the IGF2 and H19 genes

Answer 333

- single enhancer downstream of H19 gene controls the expression of both genes on maternal chromosome: genes and regulatory sequences are not methylated, so CTCF binds to insulator blocking activation of IGF2, but allowing for the activation of H19 on paternal chromosome: insulator and promoter region of H19 gene is methylated. CTCF cannot bind to insulator, and activator is able to active transcription of IGF2. - thus, due to mthe methylation of its promoter, the activator cannot active H19

Question 334

draw the mechanism of IGFR2 as an example of noncoding RNA mechanism of imprinting

Question 335

consequences of mutations in imprinted genes

Answer 335

- In regular genes, a mutation in one allele can often be compensated by the other normal allele. - In imprinted genes, since one allele is silenced, a mutation in the active allele acts like a dominant mutation - A mutation in the silenced allele is not expressed despite being present in the genome

Question 336

look over pedigrees of mutations in imprinted genes

Question 337

Prader-Willi syndrome symptoms

Answer 337

obese, small hands and feet, eats uncontrollably, does not mature sexually, short stature, mental retardation

Question 338

Angelman syndrome

Answer 338

developmental delays, severe mental and motor retardation, prominent jaw, happy disposition

Question 339

genetic cause of PWS

Answer 339

A deletion of the paternal copy of 15q11–q13. The same region on the maternal chromosome is silenced by imprinting.

Question 340

genetic cause of AS

Answer 340

A deletion of the maternal copy of 15q11–q13. The paternal allele of a key gene, UBE3A, is silenced in neurons due to imprinting. No active UBE3A in neurons → leads to AS.

Question 341

How are all living forms related?

Answer 341

- evolution has conserved basic strategies of development across multicellular eukaryotes - many homologous proteins have highly conserved functions

Question 342

give examples of homologous genes in different organisms

Answer 342

- eyeless (Drosophila), Pax-6 (mouse), and Aniridia (humans) genes are homologous - Pax-6 and Aniridia wild-type genes can direct eye development in Drosophila

Question 343

distinguish between forward and reverse genetics

Answer 343

Forward: Phenotype → Find gene - Mutagenize, screen for trait, map gene - Use when you know the trait but not the gene Reverse: Gene → Find phenotype - Knockout/mutate gene, observe effect - Use when you know the gene but not its function

Question 344

what is an example of mutagenesis screens in organisms?

Answer 344

- motor axon guidance mechanisms in Drosophila. - scientists mutagenise C. elegans, observe the phenotype, then try and identify the gene responsible for each phenotype

Question 345

what is a modifier mutagenesis screen?

Answer 345

type of genetic screen used to find genes that influence the severity or expression of a known phenotype, rather than causing the phenotype on their own.

Question 346

define redundancy

Answer 346

two or more genes perform overlapping or similar functions, so that loss of one gene has little or no effect on phenotype

Question 347

What does the "modifier mutagenesis screen" using sev::Ras^G12V in Drosophila eyes reveal about genetic interactions?

Answer 347

- Wild type: Normal eye structure. - sev::Ras^G12V: Rough eye due to hyperactive Ras signaling. - Enhanced phenotype (E⁻/E⁺; sev::Ras^G12V): worsened mutant phenotype → E is a negative regulator of Ras. - Suppressed phenotype (S⁻/S⁺; sev::Ras^G12V): More normal eye → S is a positive regulator of Ras.

Question 348

Use of Genome wide screens

Answer 348

- we can design RNAs that can target specific genes and inactivate them, similar to a knockout - this produces a phenocopy of a loss of function mutation

Question 349

define a phenocopy

Answer 349

a phenotype that mimics the effects of a gene knockout, caused by methods like RNAi or CRISPR.

Question 350

4 ways in which we can analyse developmental pathways

Answer 350

Nature of the encoded protein: - we can infer amino acid sequence from nucleotide sequence and use computer searches to identify known motifs Location and timing of gene expression: - during development, where and when is the mRNA found? Location of the protein product: - during development, where and when is the protein found? Developmental phenotypes: - what cells or tissues are affected by loss-of-function?

Question 351

two methods to follow the localisation of proteins

Answer 351

- attach antibodies to the protein - tag the proteins with GFP

Question 352

why must the interactions of genes in a developmental pathway be determined?

Answer 352

genes don't work in isolation, and many biological processes are complicated and require the coordinated action of many genes

Question 353

two key steps to ordering genes in a pathway

Answer 353

analysis of effects of one gene on expression of another gene: - does a mutation in one gene affect the level or distribution of mRNA or protein from another gene? analysis of double mutants - epistatic interactions: - do mutations in two different genes define successive steps in a pathway?

Question 354

give an example of the impacts that gene products can have on the expression of other genes

Answer 354

- staining of Drosophila wing imaginal disks for wingless protein (Wg, green) and vestigial protein (Vg, red) - wild-type produces a different staining pattern than wingless mutant - this suggests that the wingless gene product is required for the expression of the vestigial gene

Question 355

2 requirements for an epistasis analysis:

Answer 355

- phenotypes of the two mutants must differ - alleles must either be null or constitutive

Question 356

null allele

Answer 356

A mutant allele that results in complete loss of function of the gene.

Question 357

constitutive allele

Answer 357

A mutant allele that causes the gene to be continuously active, regardless of normal regulatory signals.

Question 358

use the sevenless signalling pathway as an example of epistasis analysis

Answer 358

- the phenotype of the double mutants reveals epistatic interactions - in a double mutant, the phenotypes the same as the Ras^G12V mutant, therefore seven less is upstream of Ras - the downstream gene is the one that is epistatic - thus, Ras is downstream and epistatic to sevenless ('masks' sevenless)

Question 359

what is the programmed cell death pathway and how was it understood?

Answer 359

- eliminates unwanted or damaged cells - was understood by epistatic analysis screens

Question 360

relationship between embryonic and adult body axes in drosophila

Answer 360

each embryonic segment defines a specific structure in the adult: 3 head segments, 3 thoracic segments, 8 abdominal segments

Question 361

who made discoveries concerning the genetic control of early embryo development

Answer 361

Christiane Nusslein-Volhard, Eric Wieschaus, Edward B. Lewis

Question 362

What two mutagenesis screens were conducted to identify genes that control embryonic development?

Answer 362

1. Screening for abnormal embryos in homozygous mutant females - Identified recessive mutations in maternal-effect genes 2. Screening for abnormal homozygous mutant embryos - Identified recessive mutations in three classes of zygotic segmentation genes

Question 363

Four classes of genes responsible for segment formation in drosophila embryos

Answer 363

Function in a hierarchy that progressively subdivides the embryo into successively smaller units - maternal genes - gap genes - pair-rule genes - segment polarity genes

Question 364

maternal genes

Answer 364

- expressed by the mother - mRNAs deposited in egg but not translated until after fertilisation - products of maternal effect genes establish morphogenic gradients in the egg - these gradients ensure that gap genes are expressed only in certain broad regions of the embryo

Question 365

gap genes

Answer 365

- expression is controlled by maternal gene products - expression begins at syncytial blastoderm stage - activate pair-rule genes in a series of seven stripes

Question 366

pair-rule genes

Answer 366

- seven zones of expression are controlled by gap and maternal gene products - levels of pair-rule gene products restrict the expression of segment polarity genes to a series of 14 stripes, one per segment

Question 367

segment polarity genes

Answer 367

- expression in 14 segments is controlled by pair-rule gene products - this divides the embryo into 14 segment-sized units

Question 368

what controls the anterior and posterior patterning in the drosophila embryo?

Answer 368

two maternal-effect gene products which are morphogens: bicoid (bcd) and nanos (nos)

Question 369

define a morphogenetic

Answer 369

a substance that defines cell fate in a concentration-dependent manner

Question 370

how do bcd and nos work?

Answer 370

- bcd and nos are transcribed by the mother and their mRNAs are localized to opposite poles of the oocyte - bcd and nos mRNAs are not translated in the embryo until after fertilisation - each protein forms a gradient in the embryos (diffusion)

Question 371

bcd protein gradient

Answer 371

bcd is highest at anterior and lowest at the posterior

Question 372

nos protein gradient

Answer 372

nos is lowest at anterior and highest at the posterior

Question 373

localisation of bicoid mRNA and protein

Answer 373

- bcd mRNA localizes to the anterior pole of the oocyte - bcd protein diffuses from the anterior pole of the embryo to produce an anterior-to-posterior gradient

Question 374

evidence that bicoid is the anterior morphogenetic

Answer 374

- dosage of maternal bcd gene determines how much of the embryo becomes head structures (the more protein in the anterior, the greater the size of the segment) - bicoid null mothers produce embryos that lack all head and thoracic structures

Question 375

describe and draw the distribution of RNA and protein products of maternal-effect genes within the early drosophila embryo

Answer 375

- bicoid protein activates the expression of hunchback gene and represses translation of caudal mRNA - this causes posterior-to-anterior gradient of caudal protein - nanos protein represses the translation of hunchback mRNA - this causes anterior-to-posterior gradient of hunchback protein

Question 376

how is segment number further specified?

Answer 376

by zygotic genes: - bicoid, hunchback, and caudal proteins are transcription factors that control the spatial expression of zygotic genes - zygotic gene expression begins in the syncytial blastoderm stage

Question 377

three classes of zygotic segmentation genes

Answer 377

- gap genes - pair-rule genes - segment polarity genes

Question 378

look at slide 30

Question 379

two classes of pair-rule genes

Answer 379

primary pair-rule genes and secondary pair-rule genes

Question 380

primary pair-rule genes

Answer 380

- expression is controlled by transcription factors encoded by maternal genes and zygotic gap genes - upstream region of each pair-rule gene has multiple binding sites for transcription activation/repression

Question 381

secondary pair-rule genes

Answer 381

- expression is controlled by transcription factors encoded by other pair-rule genes

Question 382

how are pair-rule genes expressed at the early blastoderm stage?

Answer 382

- in seven stripes - two segment periodicity: each stripe has two segments

Question 383

stripe 2

Answer 383

eve transcription is activated by Bcd and Hb, but repressed by giant (Gt) and Kruppel (Kr) proteins

Question 384

how is individual pair-rule stripe formation controlled?

Answer 384

by combinations of maternal-effect and gap proteins (see slide 32_

Question 385

distribution of engrailed proteins in 14 stripes

Answer 385

- segment polarity genes are expressed in stripes that are repeated with single segment periodicity (one stripe per segment) - interactions between various polarity genes maintains the periodicity

Question 386

many of the Drosophila A-P axis genes that contribute to pattern formation code for

Answer 386

transcription factors

Question 387

genetic hierarchy leading to segmentation in drosophila

Answer 387

in successive levels of the hierarchy, genes are expressed in narrower bands

Question 388

how is segment identity established by homeotic genes?

Answer 388

- transcription of homeotic genes is controlled by gap, pair-rule, and segmentation genes - at the cellular blastoderm stage, each homeotic gene is expressed within a subset of body segments - homeotic genes are master regulators that control transcription of many genes responsible for development of segment-specific structures

Question 389

homeotic transformation

Answer 389

when one body part develops as if it were another, due to mutations in homeotic (Hox) genes, which control body plan identity during development.

Question 390

example of a homeotic transformation in drosophila

Answer 390

Wild type wing vs bithorax mutant vs postbithorax mutant

Question 391

how are hox genes expressed?

Answer 391

in spatially restricted domains

Question 392

mammalian Hox genes are organised into four gene clusters:

Answer 392

each on a different chromosome: HoxA HoxB HoxC HoxD

Question 393

how do we know that Hox genes play an important role in developmental patterning of all animals?

Answer 393

all animal genomes - even those of sponges - contain Hox genes

Question 394

why is it not possible to just mutagenise the wild-type organism in a modifier mutagenesis screen?

Answer 394

if you just mutagenise the wild type, you may have a whole bunch of different mutations, but if there's redundancy you won't see the phenotype you are studying

Question 395

what is the function of the sev gene in Drosophila?

Answer 395

sev is a receptor tyrosine kinase that activates Ras signaling to specify the R7 photoreceptor.

Question 396

what is the function of the Ras gene in Drosophila?

Answer 396

When sev is activated by its ligand, it triggers a cascade that activates Ras, which in turn promotes cell differentiation (the specification of the R7 photoreceptor neuron).

Question 397

what is Ras^G12V?

Answer 397

gain of function mutation - this mimics constant "on" signaling, so R7 cells develop even without the proper upstream signal, or develop abnormally, causing things like a rough eye phenotype.

Question 398

define a maternal-effect gene

Answer 398

genes that are 100% inherited from the maternal side