Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MBB262 > Anderson > Flashcards

Anderson Flashcards

1
Q

What is the principle of maximum parsimony?

A
  • simplest hypothesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What kind of hypothesis do you always have for transmission genetics?

A
  • genetic hypothesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is hypothesis testing carried out for transmission genetics?

A
  • genetic hypothesis leads to prediction
  • in some cases can use observed no.s to give idea of genetic hypothesis
  • compare prediction with observed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a null hypothesis?

A
  • diff between O and E no.s can be explained by chance alone

- no signif diff between O and E

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is P (p values)?

A
  • probability of obtaining observed deviation, or even bigger, assuming null hypothesis correct
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What gives a simple approximation of P?

A
  • chi-squared
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does a p value of greater than 0.05 mean?

A
  • no signif deviation from expectation at 5% level
  • if did 20x, expect 1x to get deviation bigger, can accept null hypothesis
  • no reason to reject it, can’t say its proven, just failed to prove it wrong
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does a p value of less than 0.01 mean?

A
  • signif deviation from expectation at 1% level

- if did 100x and genetic hypothesis correct, only expect deviation 1x, so quite unlikely result just by chance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does a p value of less than 0.05 mean?

A
  • signif deviation from expectation at 5% level
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why is there a grey area for p values between 0.01 and 0.05?

A
  • can’t just assume one thing if just below threshold and opp if just above threshold
  • chi-squared only aid to thinking about signif, have to weigh up data biologically
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where are qualitative differences in phenotype found?

A
  • in “conventional” Mendelian analysis

- prod by allelic variation at single locus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are quantitative characters influenced by?

A
  • usually several to many genes and env
  • look at real pop (not in lab)
  • several oligogenes or many polygenes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is a polygene?

A
  • 1 member of group of genes contributing to quantitative character, NOT group of genes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is an oligogene?

A
  • 1 member of group of genes, w/ fewer members but each are making bigger contribution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is a QTL (quantitative trait locus)?

A
  • section of DNA that correlates w/ variation in phenotype
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why is unlinked always the default hypothesis?

A
  • simplest explanation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the 2 types of variation?

A
  • continuous

- discontinuous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is a meristic character?

A
  • countable quality w/ integer values
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

When are genes said to act additively?

A
  • when sub of 1 allele for another alters phenotype value by certain amount irrespective of other alleles present at same or other loci
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What simplifying assumptions are made in additive model for polygenic inheritance?

A
  • 3 genes
  • each making same contribution
  • no env contribution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the additive model for polygenic inheritance (EXAMPLE)?

A
  • height of hypothetical plant controlled by 3 genes
  • a1, b1, c1 each add 1cm
  • a2, b2, c2 each add 2cm
  • a1a1 = +2cm
  • a1a2 = +3cm
  • a2a2 = +4cm
  • then to all of these:
    –> b1b1c1c1 = +4cm
    –> b2b2c2c2 = +8cm
  • no dominance, no epistasis
    P1 x P2 = a1a1b1b1c1c1 (+6cm) x a2a2b2b2c2c2 (+12cm)
    F1 = a1a2b1b2c1c2 (+9cm)
    F2 = 8 phenotypes in ratio 1:6:15:20:15:6:1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the general features of the additive model for polygenic inheritance?

A
  • F1 mean exactly intermediate between P1 and P2
  • F2 mean same as F1
  • variation greater in F2 than F1
  • extremes in F2 correspond to P1 and P2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How do extremes in F2 correspond to P1 and P2 (additive model for polygenic inheritance)?

A
  • for n genes proportion F2 as short as short parent = (1/4)^n
  • which is a v big no.
  • so unless no. genes v small or vast no. in F2 gen, then prob not going to see extremes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Why is scale transformation needed?

A
  • common problem to find non-normal distributions = skewed distributions
  • not a big problem just need to define quantitative character in way that will fit, eg. log(score)
  • makes curve much more symmetrical so maths will now work for it
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the components of total phenotypic variance (VP)?

A
  • = genetic (VG) added to environmental (VE) component
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is heritability in the broad sense?

A
  • H^2 = VG/VP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What does broad sense heritability show?

A
  • indicates proportion of phenotypic variance attributable to genetic variation
  • property of particular pop in particular env
  • not good predictor of success in selective breeding
  • only part of VG is due to additive effects of gene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Why is only part of VG due to additive effects of gene?

A
  • VG = VA (additive component) + VD (dominance component) + VI (interaction/epistasis component)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the range of values broad sense heritability can have, and what does a value of 1 mean?

A
  • 0 to 1

- 1 means all variance due to genetic component

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Why dont VD and VI operate in way modelled?

A
  • 2 interacting alleles separated in mitosis
  • so interact w/ other alleles when fertilised
  • could decrease superiority due to diff allele combo, so inherently unpredictable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is narrow sense heritability, h^2?

A
  • h^2 = VA/VP

- good predictor of success, as focusses on VA (1 component of VG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How can estimation of narrow sense heritability be used in selective breeding?

A
  • test effect of selection on pop involved
  • choose best by taking from above certain point in distribution = truncation point
  • mean of offspring will be higher than original mean
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How is realised heritability (h^2) and its components calc, and what does a positive value mean?

A
  • response to selection / selection differential
  • response to selection = mean of offspring - original mean
  • selection differential = mean of parents - original mean
  • +ve value shows trying to increase phenotypic score (-ve means opp)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How can narrow sense heritability be estimated using a graph?

A
  • DIAG*
  • plot mean of offspring against mid parent value
  • slope gives h^2
  • for some characteristics (eg. egg prod) may need to use regression of offspring on 1 parent, so h^2 will be 2x slope
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What are the typical values of h^2 and what do they mean?

A
  • high (>0.5) –> more than half contributed by VA
  • medium (0.2-0.5) –> still a signif contribution by VA
  • low (<0.2)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the breeders equation?

A
  • response to selection = h^2 x selection differential
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the limits of selection?

A
  • not poss to improve phenotypic scores indefinitely by cont selection, as favourable alleles may all approach fixation
  • -> mostly makes use of existing genetic variation, VA will decrease, so if VE stays same then h^2 will also decrease
  • selection for 1 trait may lead to correlated response in another trait affecting fitness (eg. selection for extreme size often leads to loss of fertility, so problem maintaining pop)
  • inbreeding depression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How is selective breeding diff to natural selection?

A
  • over short period of time (few gens)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

How does inbreeding depression occur as a result of selective breeding?

A
  • picking ‘best’ encourages inbreeding

- increased freq of deleterious recessive alleles, as having 2 copies becomes more likely

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is a solution to inbreeding depression?

A
  • select 2 lines (may have inbreeding)
  • cross them
  • hope recessive alleles complement each other and gen F1 hybrid w/ superior phenotype
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

How can genotype and environment interact?

A
  • superiority of 1 genotype over another may not be maintained in all envs
  • DIAG*
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Why does a heritability of 0.7 for maize height not indicate that 70% of height of each plant is determined by genes acting additively and 30% by environment?

A
  • means 70% variance in maize height in typical pop, due to genetic variation for genes acting additively
  • 30% due to diffs in envs experienced by diff plants and interactions between alleles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

If h^2 for maize height = 0.7 and h^2 for ear length = 0.17, is it true that genes are more important in determining height than ear length?

A
  • no
  • deletion of relevant genes for either character might be lethal
  • both important to us, ear length could have undergone more selection so even be more important
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

If heritability for maize height is 0.7, is it true that there is little scope for increasing height by changing env?

A
  • no
  • high heritability indicates diff in envs experienced by individuals in typical pop contribute less to overall variance in genotype
  • may still be scope for great improvement w/ env quality, unpredictable from heritability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Does high heritability for maize height indicate if 1 pop has high higher av score than other that it must carry superior genes?

A
  • no

- could only conclude this if know envs identical and even then change in env could reveal diff norms of reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

How is heritability in humans diff?

A
  • heritability calcs assume env varies independently of genotype
  • but family members share similar genes and envs
  • regression of offspring on parents shows familiarity rather than heritability (shown by slope)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How does heritability vary for twins raised together?

A
  • dizygotic and monozygotic twins share similar env to approx same extent
  • but dizygotic twins share only 50% of genes
  • so diffs in degrees of similarity between monozygotic and dizygotic twins may be attributed to genes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is concordance?

A
  • way of comparing degree of similarity between twins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is a threshold trait?

A
  • DIAGS*
  • can plot threshold against liability
  • there is a threshold liability
  • liability influenced by genes and env

OR

  • plot freq against no. predisposing alleles
  • threshold zone where may or may display phenotype
  • then disease where they will defo show phenotype
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

How can H^2 be calc for twins (assuming MZ and DZ share env to same extent)?

A
  • 2 (tMZ - tDZ)

- where tMZ = phenotypic correlation of monozygotic twins and tDZ = phenotypic correlation of dizygotic twins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How are quantitative genes identified in humans?

A
  • can’t do controlled crosses which allow detection by linkage to marker
  • eg. originally RFLPs (restriction fragment length polymorphisms)
  • eg. now SNPs (single nucleotide polymorphisms)
  • DIAG*
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What does QTL mapping involve?

A
  • taking 2 lines where can follow many marker genes
  • prod F1
  • then F2 or backcross w/ parent (comparing homozygote w/ heterozygote)
  • then need method to recognise 2 distributions are signif diff
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What happens if the QTL and marker recombine, and what does this show about out ability to detect QTLs?

A
  • reduce the diff in phenotypic score between homozygotes for marker alleles
  • so ability to detect QTL determined by magnitude of effect by QTL on phenotypic score, and extent of recombination between marker and QTL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What does finding QTLs through linker-based analysis req/involve?

A
  • large no. markers distributed across all chromosomes, at least every 5-10cM (can be done easily)
  • test each maker for signif diff between av phenotype scores for 2 homozygotes
  • or in practise usually homozygote and heterozygote in backcross
  • log10 (prob of obs result if QTL assoc w/ marker / prob of obs result if QTL not assoc w/ marker)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What does identifying a QTL actually show?

A
  • doesn’t identify gene
  • just region around markers where think gene making contribution
  • don’t know if more than 1 gene, but no tendency for QTLs to cluster together, distributed throughout genome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

After a QTL identified, how is the gene identified?

A
  • fine mapping
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

How is fine mapping carried out?

A
  • for each marker showing signif diff, gen and compare lines that are isogenic except in region of suspected QTL and recombinant in this region
  • congenic = isogenic (nearly)
  • want flanking markers DIAG
  • genotype recombinants prod to find COs (tells us CO is in QTL) DIAG
  • look specifically at chromosome in region where we know QTL is
  • can identify gene if narrow region down to 1 or a few genes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What has been used instead of linkage analysis in humans?

A
  • GWAS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

How is GWAS carried out for human diseases?

A
  • range of DNA markers around genome, up to half a mil SNPs
  • looked at many SNPs and got statistical analysis essentially equivalent to chi-squared –> log10 (P)
  • null hypothesis is no assoc between marker and phenotype
  • can’t use 5% level as looking at so many SNPs, so need v low probability threshold
  • assoc clear if SNP is in QTL
  • otherwise detection of QTLs dep on LD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

How can SNPs be used to detect nearby QTLs is assoc studies?

A
  • linkage disequilibrium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is linkage equilibrium, and when is it expected?

A
  • state where random assoc of alleles at any 2 loci

- expected in infinite pop w/ random mating and no selection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

If allele freqs for A, a, B, b are p1, p2, q1, q2 respectively, what haplotype freqs will be gen by random assoc of alleles of 2 genes, and why is this true even if genes are linked?

A
  • fAB = p1q1
  • fAb = p1q2
  • faB = p2q1
  • fab = p2q2
  • haplotypes gen by meiosis in wide variety of genotypes, so parental combos in 1 meiosis will be recombinants in another
  • DIAG*
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is linkage disequilibrium?

A
  • non random assoc of alleles at 2 loci

- deviation form linkage equilibrium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

In linkage disequilibrium, what is D?

A
  • deviation from linkage equilibrium
65
Q

What is the range for D?

A
  • can be +ve or -ve (but eg. if more fAB then there is less fAb, as same no. A alleles in pop)
  • min = 0
  • max = Dmax and depends on allele freqs and particular pop
66
Q

How can you calc D?

A
  • D = fAB - (fA x fB)
    OR
  • D = (fAB x fab) - (fAb x faB)
67
Q

What does it mean if D>0?

A
  • fAB, fab greater than expected at eq
  • fAb, faB less than expected at eq
  • Dmax would correspond to pop in which fAb or faB reaches 0
  • so Dmax = min | (fA x fb) , (fa x fB) |
68
Q

What does it mean if D<0?

A
  • fAB, fab less than expected at eq

- so Dmax = min | (fA x fB) , (fa x fb) |

69
Q

Why can’t we directly compare D values?

A
  • max value varies, so don’t know if we have small or large value
70
Q

How can D values be compared?

A
  • use normalised value of D
  • D’ = D / Dmax
  • range is 0-1
71
Q

What is an alt measure of D?

A
  • correlation coefficient (r^2) = D^2 / fA x fB x fa x fb
  • range is 0-1
  • NOT equal to D’
72
Q

How can linkage disequilibrium arise?

A
  • most commonly new mutation
  • mutant allele initially assoc w/ particular allele of each closely linked polymorphic locus
  • assoc breaks down as recombination assoc mutated allele w/ all poss alleles of linked genes
  • decay of LD for 2 loci depends upon recomb in double heterozygotes
73
Q

How does linkage disequilibrium decay?

A
  • for 2 loci dep on recombination in double-heterozygotes
  • exponential over pot many gens
  • rate of decay dep on recombination rate (r) between loci
  • new value of D in next gen: D1 = D0 (1-r)
  • new value of D after t gens: Dt = D0 (1-r)^t
  • bigger R gives lower values on graph DIAG
74
Q

What is req for a Manhattan plot for GWAS?

A
  • need large no. samples for affected/unaffected (typically >10,000)
  • need large no. markers –> ≈ 13x10^6 common SNPs, in practise ≈ 5x10^5 TAG SNPs
75
Q

What is the missing heritability?

A
  • many QTLs still to be discovered
  • lots of VG not accounted for by things we can test for, believe there are many genes which have a small effect and can’t measure this
76
Q

What are haplotype blocks?

A
  • genome effectively divided into blocks where v high amount of linkage diseq
  • COs tend to occur at recombination hotspots
  • so SNPs in GWAS identify haplotype blocks, in which linkage diseq maintained over many gens
  • TAG SNP used as proxy for whole block, as CO unlikely to occur w/in block
  • DIAG*
77
Q

What are the most common diploid model organisms?

A
  • Drosophila
  • mouse
  • C. elegans
  • Arabidopsis
78
Q

Why can’t simpler organisms like E. coli be used as models for human disease?

A
  • too far from humans to be useful
79
Q

What is the problem w/ using diploids as model organisms?

A
  • difficult to detect and therefore isolate recessive mutations
80
Q

What are the common features of model organisms?

A
  • easy to culture and cross
  • short life cycle
  • many progeny
  • easy to mutagenise
  • small genome (not as important now seq cheaper and easier, but small still easier to analyse)
81
Q

Why are model organisms more commonly used once they have become well established?

A
  • genetically well characterised
  • eg. genome seq, genetic map
  • “genetic tricks”
82
Q

How is life cycle length an important factor in selecting an approp model organism?

A
  • yeast shortest so may be best choice if approp
  • but Drosophila still short comp to mice and humans
  • and mice short comp to other mammals, if need mammalian model
83
Q

What are genetic tricks?

A
  • to specifically exploit biology of organism

- diff for each organism, but may be used for same purposes

84
Q

Why is Drosophila used as a model organism?

A
  • 1 of best characterised diploid organisms
  • small and easy to culture
  • short life cycle
  • prod 10s of progeny
  • undergoes complete metamorphosis, have imaginal discs = structures identifiable in larvae, recognisably diff from laval cells which aren’t in adults
85
Q

Where are polytene chromosomes commonly found?

A
  • Drosophila

- eg. salivary glands of larva

86
Q

What are polytene chromosomes and how are they formed?

A
  • repeated rounds of rep in absence of division
  • each chromosome may undergo up to 10 rounds of rep, giving up to 1024 DNA molecules arranged side by side
  • homologous chromosomes undergo somatic assoc, so total no. DNA molecules packed in parallel can be up to 2048
  • some seqs undergo fewer (7-8) rounds of rep, particularly ribosomal (rDNA) and heterochromatin
87
Q

What is the structure of polytene chromosomes?

A
  • centromeres assoc at chromocenter, which is made up of centromeric heterochromatin
  • so complete chromosome complement of interphase cell visualised as 5 long arms (X, 2L, 2R, 3L, 3R) and 1 stump (4)
  • Y chromosome not visible, as heterochromatic, under replicated and present w/in chromocenter
88
Q

How can regions of Drosophila genome be identified w/ high res?

A
  • banding patterns in polytene chromosomes
  • 5000-6000 dark bands, alt w/ light interbands
  • much more banded than humans
89
Q

How have cytological maps been correlated w/ linkage map?

A
  • rearrangement breakpoints can sometimes be assoc w/ mutations that occur when breakpoint disrupts a gene
90
Q

How are inversions CO suppressors?

A
  • small inversions may inhibit pairing of homologues in inversion heterozygote –> forms bubble so chromosome can’t twist DIAG
  • larger inversions allow formation of inversion loop (where COs can occur), but inversions lead to duplications and deletions so CO products inviable
  • pericentric and paracentric inversions also lead to duplications and deletions, so CO products inviable
91
Q

What are the features of a ClB chromosome?

A
  • CO suppressor –> inversion
  • recessive lethal mutation (ensures balancer homozygotes automatically removed from pop)
  • Bar eye -> dominant visible mutation (so can track chromosome in crosses)
92
Q

How is a ClB stock maintained?

A
  • DIAG*
  • cross female ClB/WT w/ male WT
  • prod:
  • -> female Bar eyed
  • -> female WT (removed after each gen)
  • -> male w/ ClB (DIE)
  • -> male WT
93
Q

How can the ClB chromosome be used to isolate recessive lethals on the X chromosome?

A 
*DIAG*
Cross 1:
- cross female ClB/WT w/ male mutated test chromosome 
- prod:
--> female Bar eyed
--> female WT
--> male w/ ClB (DIE)
--> male WT

Cross 2: (new mutation on test chromosome)

  • INDIVIDUALLY cross Bar eyed female progeny from cross 1 w/ male WT
  • prod:
  • -> female Bar eyed
  • -> female WT
  • -> male w/ ClB (DIE)
  • -> male w/ mutated test chromosome (DIE if new recessive lethal)
  • so looking for absence of males from progeny of individual femals
94
Q

How can the ClB chromosome be used to isolate autosomal recessive lethals?
(typically 3 step process)

A

DIAG
Cross 1:
- balancer stock females (w/ dominant marker) x mutagenised males
- progeny of interest have balancer chromosome from mother and mutagenised test chromosome from father (identified by dominant visible)

Cross 2:

  • individual cross 1 progeny females x male balancer stock
  • prod multiple progeny carrying same test chromosome and the balancer

Cross 3:

  • cross heterozygotes for same test chromosome
  • prod:
  • -> homozygous for ClB (DIE)
  • -> heterozygotes for ClB and test chromosome (form self maintaining balanced lethal stock, heterozygous yet pure breeding)
  • -> homozygotes for test chromosome (if new recessive lethal then DIE)
95
Q

What was the aim of the Heidelberg screens?

A
  • saturate genome and isolate mutations for all genes that could be mutated
  • diff systems for isolating mutations on diff chromosomes
96
Q

How is Drosophila eye colour determined?

A
  • DIAG*
  • 2 pathways
  • 1 prod brown, cn mutation in this causes cinnabar eyes
  • 1 prod bright red, bw mutation in this causes brown eyes
  • both pathways together cause WT red eyes
  • blocking both pathways gives white eyes
97
Q

What was the strategy for screening recessive lethal mutations on chromosome 2?

A
  • DIAG*
  • used Cy (curly wings) as dominant visible on balancer chromosome and dominant temp sensitive mutation on normal chromosome

Cross 1:

  • cross female w/ balancer and normal chromosome w/ Ts w/ males homozygous for bw and cn
  • prod:
  • -> curly wings, red eyes
  • -> normal wing, red eyes (IGNORE)

Cross 2:

  • cross F1 male progeny INDIVIDUALLY w/ female balancer and normal chromosome w/ Ts
  • prod:
  • -> homozygotes for balancer (DIE)
  • -> curly wings, red eyes (heterozygotes for bw and cn)
  • -> balancer and normal w/ Ts (DIE at high temp)
  • -> test and normal w/ Ts (DIE at high temp)

Cross 3:

  • cross Cy//m, bw, cn w/ normal//m, bw, cn
  • prod:
  • -> 1 homozygote for balancer (DIE)
  • -> 2 curly wings, red eyes = Cy//m, bw, cn (new balanced lethal stock)
  • -> 1 normal wings, white eyes (or DIE if new recessive lethal)
98
Q

When screening for recessive lethal mutations on chromosome 2, why did cross 2 have to be done a particular way round?

A
  • RFs vary between males and females
  • Drosophila extreme eg. of this –> no COs in males
  • wouldn’t matter in other species
99
Q

What are mice useful for?

A
  • large scale mutagenesis screens poss using balancer stocks

- balancers engineered in ES cells using Cre-loxP tech

100
Q

What is the overall strategy for engineering balancers in mice, using Cre-loxP tech?

A
  • introduce 2 loxP sites sequentially, in opp directions, at defined positions on chosen chromosome in mouse ES cells
  • Cre transiently expressed on transfected plasmid to cause inversion as result of recombination specifically between loxP sites
101
Q

Why does CreA provide an advantage in determining breakpoints?

A
  • can decide where want breakpoints to occur for inversions, instead of at random
  • DIAG*
102
Q

How is the targeting vector inserted into chromosome? (gen mouse balancer chromosomes)

A
  • DIAG*
  • targeting vector has 2 regions of homology w/ chromosome at desired inversion breakpoint
  • targeting vectors designed to disrupt and inactivate gene at each target site, therefore creating recessive lethal genotype that’s assoc w/ balancer chromosomes
103
Q

What are the components of targeting vector? (gen mouse balancer chromosomes)

A
  • DIAG*
  • Neo = selectable marker in ES cells
  • loxP = future inversion breakpoint
  • 5’ HPRT = half selectable marker in ES cells (3’ HPRT in other vector, 2 halves arranged so recombination between loxP sites will gen complete HPRT gene w/ loxP site as intron) –> allows selection for ES cells w/ successful inversions, as HPRT expression allows recombinants to grow in selective medium (HAT)
  • Ag = dominant visible marker in mice
104
Q

What is the structure of a blastocyst, into which ES cells are injected?

A
  • DIAG*
  • trophectoderm forms outer ring = gives rise to placenta etc.
  • ES cells injected into ICM (inner cell mass)
105
Q

What is a chimera?

A
  • individual from more than 1 zygote
106
Q

How do we generate and identify transgenic adult mice heterozygous for engineered balancer chromosome?

A
  • cross chimaera (ccaa and CCAA) w/ albino (ccaa)
  • prod albino and agouti (CcAa) in unknown ratio
  • w/in agouti progeny 1:1 ratio of balancer chromosome (lighter tails and ears) to normal agouti
107
Q

What is the gene pool?

A
  • sum total of breeding pop genomes
108
Q

How is the freq of an allele calculated?

A
  • eg. for freq of A (=p)
  • no. of A alleles / 2N
  • where 2N is total no. copies of that gene in gene pool
  • p will also = freq A homozygotes + 1/2 all poss heterozygotes for A
109
Q

How can H-W be proved?

A
  • let fA = p ; fa = q ; p+q=1
  • assume p, q same in males and females (reasonably in most cases, can prove w/o just req extra step)
  • Aa x Aa –> p^2 + 2pq + q^2
  • if consider freqs of matings between diff genotypes then see freqs of 3 diff genotypes remain exactly same from 1 gen to next
110
Q

How long does it take to achieve H-W eq for an autosomal gene?

A
  • 1 gen
111
Q

How is H-W eq reached for multiple alleles?

A
  • same way, assign letters p, q, r etc.

- sum total of results of cross will = 1

112
Q

How is H-W eq reached for sex-linked genes?

A
  • genotype freqs in XX females follow H-W
  • XY males hemizygous for sex-linked genes, so genotype freqs reflect allele freqs
  • allele freqs in males and females same at H-W eq, but don’t reach eq in 1 gen
  • in males in any 1 gen, freq same as females of previous gen
  • in females in any 1 gen, freq is mean of male and female freqs in prev gen
  • X chromosomes being exchanged
  • final freq of allele in both sexes is weighted mean of original freqs (females double weighted as 2 X chromosomes)
113
Q

For sex-linked genes, what proportion of rare alleles are in homozygotes/heterozygotes?

A
  • few homozygotes for rare alleles, mainly carried in heterozygotes
  • DIAG*
114
Q

What is Darwinian fitness (W)?

A
  • relative reproductive ability of genotype

- W=1 for genotype prod most offspring

115
Q

What is the selection coefficient (s)?

A
  • intensity of selection against genotype
116
Q

In incomplete dominance, what is the value of t?

A
  • 0
117
Q

What diff genotypes can be selected against in directional selection?

A
  • recessive homozygote (aa)
  • dominant allele (AA, Aa)
  • 1 allele, no dominance (Aa, aa)
118
Q

What is directional selection?

A
  • 1 allele favoured so increase in freq in pop over time –> can go towards fixation or deletion
119
Q

What is purifying selection?

A
  • directional selection can also remove new deleterious alleles
120
Q

What is an eg. of directional selection?

A
  • peppered moth
  • dark carbonaria phenotype initially rare phenotype
  • increased to over 90% in industrial revolution, over 50 years
  • classic series of studies by Kettlewell provided evidence that carbonaria form less visible to bird predators than typica form on soot-polluted tree trunks in industrial areas
  • after clean air legislation and de-industrialisation, freq of typical form increased again
121
Q

How does rate of increase in dominant allele, A, change during directional selection?

A
  • slow when few copies of A
  • faster as more copies of A
  • slow when a mostly in heterozygotes
122
Q

What is balancing selection and an example?

A
  • selection operates to maintain balanced polymorphism in pop
  • so heterozygotes show higher fitness than either homozygote (not necessarily same but both less than 1) = heterozygote adv
  • eg. maintenance of sickle-cell allele Hb-S through resistance of heterozygotes to malarial parasite
123
Q

What is disruptive selection, and what can it lead to?

A
  • against heterozygote, both homozygotes equally fit

- can lead to speciation through reproductive isolation

124
Q

What is freq dep selection, and 2 examples?

A
  • fitness of phenotype varies with frequency
  • eg. birds have search image for prey –> rare snail shell morph may have high fitness as not recognised, as freq increase, fitness decreases, as birds start to recognise
  • eg. butterfly that protects itself by being distasteful to birds –> for strategy to work must be commonest form so birds learn to avoid, so fitness decreases as freq decreases
125
Q

How does H-W assume an infinite pop size?

A
  • assuming other H-W assumptions true, if p1 and p2 represent freq of allele A in 2 successive gens:
  • -> for infinite pop p1 = p2
  • -> for finite pop p1 ≈ p2
126
Q

What are Monte Carlo simulations, and what do they show?

A
  • computer simulations of small polymorphic pops, demonstrate random genetic drift can lead to fixation
  • for allele w/ initial freq of 0.5, equally likely to be lost or fixed
  • for allele w/ initial freq of >0.5 likely to be lost
  • initial freq of new allele will be low, so likeliest fate is to be lost, even if pot gives high fitness
127
Q

What is a pop bottleneck?

A
  • temp reduction in pop size
128
Q

What can affect pop bottlenecks?

A
  • strong genetic drift
129
Q

Why can effective pop size (Ne) be less than actual pop?

A
  • in ideal pop all individuals have same chance of prod offspring and pop size constant
  • if this not true then Ne less than actual pop
130
Q

What is the Ne for a fluctuating pop?

A
  • harmonic mean
131
Q

What is the founder effect?

A
  • when new pop arises from few founders
  • allele freqs in founders differ from parent pop due to random sampling, may not be representative of original pop
  • genetic drift in small pop
  • any rare allele inc in founding pop will have freq of at least 1/2N
132
Q

What is an example of the founder effects?

A
  • Afrikaner pop of South Africa mainly descended from 1 shipload Dutch immigrants
  • 40% current pop share surnames of original 20 settlers
  • modern pop inc 30,000 carriers of dominant gene for porphyria variegata –> much higher freq than modern Dutch pop, defective protoporphyrinogen oxidase gives severe reaction to barbiturates
133
Q

Why is mating not always random?

A
  • assortative mating

- inbreeding

134
Q

What is +ve assortative mating, and some examples?

A
  • choose mates phenotypically similar to themselves
  • eg. early and late flowering plants, human height, IQ, no. rooms in parents house
  • increased homozygosity of pop for genes affecting trait used for mate selection
135
Q

What is -ve assortative mating, and some examples?

A
  • choose mates phenotypically different to themselves
  • eg. MHC (major histocompatibility complex) in humans, being heterozygous beneficial, identified by smell
  • decreased homozygosity of pop for genes affecting trait used for mate selection
136
Q

What is inbreeding, how does it affect pops and what are some examples?

A
  • mating between relatives
  • more likely in small pops
  • increased homozygosity of pop for all genes
  • eg. 1st cousin matings in humans –> tends to approx double risk of inheriting serious recessive condition
  • selfing in plants –> doesn’t take long for whole genome to become homozygous
  • leads to inbreeding depression
137
Q

What is the inbreeding coefficient?

A
  • F = (He - Ho) / He
  • where Ho = observed heterozygosity from H-W
  • where He = expected heterozygosity from H-W
138
Q

How can we measure extent of inbreeding?

A
  • look at extent heterozygosity decreased compared to H-W

- look at extent homozygosity increased compared to H-W

139
Q

What is identity by descent (IBD) for 1st cousin matings?

A
  • chance of inheriting A1/A1 from grandparents = 1/64

- F (increase in homozygosity) = 1/64 x 4 (for 4 diff alleles) = 1/16

140
Q

How will the av coefficient of inbreeding and its rate change in a finite pop?

A
  • increase every gen

- rate increase faster in smaller pops

141
Q

How can pop structure, ie. subpops affect H-W?

A
  • H-W assumes all individual scan pot mate w/ each other
  • but many local subpops may exist, w/in which mating may be truly random
  • random genetic drift may result in fixation in diff subpops (could be in either direction)
  • -> pop as whole will show higher homozygosity than predicted by H-W
  • -> special eg. of inbreeding
  • more conventional inbreeding may also be promoted if subpops small
142
Q

When can subpops fixed for 1 gene, become fixed for others?

A
  • new mutation must be assoc w/ particular allele at each closely linked locus
143
Q

Why does recombination decrease linkage diseq?

A
  • allows other alleles to occur w/ mutation
144
Q

What is hitch-hiking?

A
  • new beneficial mutation selected for
  • for closely linked neutral gene, allele that happens to be assoc w/ new mutation also favoured
  • may occur simultaneously for no. genes in vicinity of new adv allele, resulting in selective sweep (decreases genetic variation in vicinity of new adv allele as it goes through fixation)
  • DIAG*
145
Q

What decreases the effect of hitch-hiking?

A
  • recombination, breaks assoc of beneficial mutation and neutral allele
146
Q

What is finding a selective sweep area an indicator of?

A
  • recent +ve selection event
147
Q

How can linkage diseq be maintained, instead of decaying over time?

A
  • selection for haplotypes in which tightly linked alleles show beneficial epistatic interactions
  • eg. genes for mimicry in butterflies
148
Q

What are the phenotypes of Papilio memnon butterflies?

A
  • only females show mimicry

- all males bright blue, as makes more successful at mating, even if damaging to own survival

149
Q

How is Batesian mimicry shown in Papilio memnon?

A
  • palatable species mimics distasteful one
  • at least 3 tightly linked loci in supergene postulated to account for mimicry patterns
  • putative recombinants poor mimics, so selected against
  • if freq palatable increases too much and gets more common, then system not effective
  • so often see wide variety of morphs that mimic diff distasteful species
150
Q

What is Mullerian mimicry?

A
  • distasteful species resemble one another
  • more effective at deterring predators if high freq
  • expect only 1 morph in 1 geographical location, but may be diff morphs in diff geographical locations
151
Q

What is a supergene, and their characteristics?

A
  • group of closely linked polymorphic genes in linkage diseq w/ one another
  • diff haplotypes, where each corresponds to diff phenotype
  • complex epistatic interactions
  • > 1 haplotype assoc w/ high W
152
Q

How are supergenes maintained?

A
  • if recombination (not common) then would gen haplotypes w/ low W
  • so selected against
  • therefore maintain supergene through selection against recombination
153
Q

When are supergenes found and why?

A
  • when diff morphs in same geographical location (Batesian)

- if geographically separate (Mullerian) then no chance of recombination, so have no. diff genes

154
Q

How is Mullerian mimicry shown in Heliconius numata, and what studies were carried out?

A
  • (unusually) many morphs in same location
  • aurora dominant to silvana
  • no recombination in P locus, but is to either side
  • did assoc study between series of SNPs alleles and aurora/silvana wing morphs –> found high assoc in P locus and low outside
  • looked directly for linkage diseq between SNPs using heat map (uses r^2)
  • polymorphism for inversion locked in haplotypes, so can’t undergo COs
  • aurora assoc w/ 1 arrangement caused by inversion and silvana by another
155
Q

What is a heat map?

A
  • looks at pairwise combos of particular SNPs

- to look at degree of linkage diseq between them

156
Q

How is sex-limited Batesian mimicry shown in Papilio polytes?

A
  • males don’t show mimicry and only some females do
  • single polymorphic locus that decide if females show mimicry and if they do, what morph
  • supergene locus co-localised region already known to play role in sex determination
  • in butterflies, sex determination by autosomal doublesex gene, the transcript of which shows differential splicing, gender dep on way splices
  • assoc study showed v strong assoc between morphs and doublesex gene –> suggesting supergene is only 1 gene (w/in gene polymorphism for at least 1 inversion, has tight control of COs w/in gene)
  • -> haplotypes are just alleles of this gene
  • -> each haplotype corresponds to series of specific mutations at diff points w/in gene, so to maintain allele, need inversion to suppress COs
157
Q

Why does a single crossover within an inversion loop have different effects, depending on whether the inversion is pericentric or paracentric?

A
  • paracentric inversion = centromere outside inversion
  • pericentric inversions inc centromere
  • diff effects arise from special properties of centromere
  • -> no centromere means chromosome cannot be processed on spindle and lost
  • -> 2 centromeres means chromosome will form bridge at anaphase 1 and may break
158
Q

How is change in allele freqs due to inbreeding calc?

A
  • AA = +pqF
  • Aa = -2pqF
  • aa = +pqF

MBB262 (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions