1
Q
What did Darwins theory or natural selection require?
A
Offspring to inherit information (I.e. Height, eye colour) from parents, but also required information to vary slightly from generation to generation.
2
Q
Why did medal use pure breaking plants instead of something like humans to measure offspring?
A
- most parents I.e. Humans give rise to too much variation, making it difficulty to tell exactly what info each parent passes on.
3
Q
What are pure breading plants?
A
They have been in read for several generations to produce strains that display very little variation in phenotype from one generation to the next.
- you can predict exactly how fast they will grow, how big they’ll be and what they’ll taste like etc.
- perfect for mental as you know exactly what information will be passed from parents to offspring.
4
Q
How did Mendal’s work help rule out ‘blending inheritance’ ?
A
By showing that when you crossed two pure breading lines, all of the offspring looked like one line, rather than a mix of both.
I.e. If mixing one tall pure breading with one small pure breading
Either get a tall plant or small one. Not a medium one.
5
Q
In summary what was Mendal’s suggestions?
A
Each phenotype (= the trait you can see) is determined by genotype (=the material of hereditary you can’t see).
- the genotype consists of 2 alleles (one from the father, one form the mother).
- it’s the exact combination of these alleles that determines the phenotype of the organism.
6
Q
What is the name given to an organism when both alleles in the genotype are the SAME?
A
Homozygous.
7
Q
What is the name given to an organism when both alleles in the genotype are DIFFERENT?
A
Heterozygous.
8
Q
What is the most common from of dwarfism called and what is it caused by?
A
Achondroplasia, result of dominant mutation in a growth signalling molecule.
9
Q
What is the ‘principle of segregation’ ?
A
When we cross 2 F1 individuals, we find that their alleles are divided into offspring randomly.
= only one parental allele is given, at random, to each gamete the parent produces.
10
Q
What is the ratio when we cross Tt X Tt ?
A
3:1
T: t
11
Q
What did Mendal’s do to discover the principle of random assortment? And what is it?
A
Looked at what happened when he crossed pure breading plants with 2 traits of interest ( we call these ‘dihybrid crosses’).
- the alleles of different genes are allocated to gametes independently of each other.
12
Q
What is the ratio seen with a dihybrid cross?
A
9:3:3:1
13
Q
If the organism displays a dominant trait what can its genotype be either?
How can we work out which one it is?
A
Homozygous dominant or heterozygous.
- we cross the mystery-genotype-plant with a homozygous recessive trait strain, and look at the ratio of offspring produced.
- this is known as a ‘test cross’.
14
Q
What is ‘modern synthesis’?
A
It provides a mathematical description that links evolution and genetics.
15
Q
What is Mendelian genetics?
A
Uses the term gene to refer to a unit of information, this information can be passed on to offspring according to various rules.
16
Q
What did Walter Flemming do, and how did this serve as a breakthrough for genetics?
A
Used aniline dyes to show chromosomes in the nucleus divide when the cell does; a process that Flemming called mitosis.
- we now know the cell passes through 4 main cycles of the ‘cell cycle’
17
Q
What is the G1 phase?
A
Most cells are in G1 phase, this is the normal, diploid, cell going about its business.
18
Q
What is the S phase?
A
A number of signals hormones, environmental stress and so on can tell a cell that it’s time to divide.
- the first step to nuclear division is DNA replication, which occurs during the DNA SYNTHESIS phase.
- the genome remains relatively open during the S phase, to allow the DNA machinery to access the DNA.
- lasts a couple of hours in euk. Minutes in prok.
19
Q
What is ‘n’ used to refer to?
A
Used to refer to the genetic content of a cell.
1n = the number of alleles present for a gene locus in a haploid cell.
20
Q
What does ‘C’ refer to?
A
Used to refer to the DNA content of the cell.
- 1C = the amount of DNA present in a haploid cell.
21
Q
Using n and C notation what would a diploid cell have during G1?
A
2n and 2C.
22
Q
Using n and C notation what would a cell in G2 have? And why?
A
2n and 4C. (There’s twice as much DNA in the G2 cell, as its replicated, but the same amount of genetic information- there’s still only 2 alleles per gene locus).
23
Q
What are the 5 stages of the M phase (mitosis)?
- the cell equally divides its contents between 2 daughter cells.
A
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase
24
Q
What happens in prophase?
A
The chromosomes condense and become visible. Remember they have replicated, so each chromosome consists of 2 copies (sister chromatids) held together at the centromere.
25
What happens in prometaphase?
The nuclear envelope breaks down.
26
What happens during metaphase?
All of the chromosomes line up along the middle of the nucleus (at the equatorial plate.)
27
What happens during anaphase?
each chromosome is pulled apart into its 2 chromatids.
- one chromatid goes into one daughter cell and the other goes into the other daughter cell. The chromatids are pulled apart by a spindle that attaches to the centromere.
28
What happens during telophase?
A nuclear envelope forms around each of the 2 daughter nuclei and the daughter chromosomes relax and decondense.
29
What did Theodor Boveri do?
He used microscopy to look at the patterns of chromosome inheritance in ployspermic sea urchin embryos.
- he showed that if you don't get the correct assortment of chromosomes into cells at mitosis then the daughter cells die.
30
What is the structure of chromosomes at metaphase?
(Paired sister chromatids)
- sister chromatids (each of which is a double helix).
- short arm = p arm (petit)
- long arm = q arm
Sister chromatids are joined at the centromere.
31
What is the structure of chromosomes after telophase?
Sister chromatids have separated leaving one condensed chromosome.
32
What are G bands on chromosomes?
(Condensed chromosome, Giemsa stained).
- Euchromatin (white bits)
- Heterchromatin (black bits)
33
How do chromosomes exist in diploid organisms?
In homologous pairs.
- Each of your (diploid) cell carries 2 complete copies of the genome.
- every chromosome you get from mum you get one with the same basic structure from dad.
34
Why evolutionarily are chromosomes dived up?
Genomes are too big and unwieldy to carry about in one DNA strand so evolution has divided them into smaller chunks.
35
What do homologous chromosomes have in common?
- the gene loci are in the same order on each member of a pair, but the alleles at a given gene locus don't have to be the same.
36
What did Nettie Steven's and Edmund Wilson do?
Uses chromosomes spread to look at male and female karyotypes and identify sex chromosomes.
37
Why does mitosis fit with Mendal's principle of segregation?
In mitosis each daughter cell receives all the alleles present in the parent. The principle of segregation suggests that gamete cells only receive half the alleles present in the parent.
38
What did Edouard Van Beneden discover?
Another mechanism of cell division, found a second mode of division that began with 2 lines of chromosomes lining up at metaphase rather than one.
39
What are the 2 lines of chromosomes at the Equatorial plate made up of?
Formed by homologous chromosomes pairing up with each other, and the process that this starts with was named 'meiosis'.
40
What are the 3 main differences between meiosis and mitosis?
I. They happen in different places- mitosis in somatic cells, meiosis in germ cells.
II. Mitosis has one cell division, but meiosis actually has 2 cell divisions.
- one immediately after the other, Meiosis I and Meiosis II.
- so mitosis produces 2 daughter cells, but meiosis produces four.
- both mitosis and meiosis start with the same amount of DNA in the cell (= 2n/ 4C produced in S phase).
> mitosis divides once so produces diploid (2n, 2C) daughter cells.
> meiosis produces haploid (n, C) gametes.
III. Homologous chromosomes don't associate with each other during the mitotic prophase. But they DO associate with each other during the prophase of the first meiosis division (=Meiosis I), as you can see in the right-handed cell of the figure above, hence the Van Beneden's two lines of chromosomes- each line contains one member of a homologous pair. This pairing up of homologous chromosomes drives an incredibly important process called recombination.
41
What is genetic?
Comes from Greek roots meaning 'race' or 'kind' and therefore the study of how and why offspring become the same 'kind' of organisms as their parents.
42
What happens during meiosis 1?
- appart from the prophase of meiosis 1 (M1) the phases are basically the same as mitosis.
43
What happens during prophase of meiosis 1?
The chromosomes condense BUT homologous chromosomes also pair up = the big difference. They do so in 5 sub-phases.
44
During prophase of meiosis 1 what are the 5 sub phases?
A. Leptotene- 'thin threads' chromosomes become visible.
B. Zygotene- 'yoked threads' homologous chromosomes pair up (synapsis)
C. Pachytene- ' thick threads' crossover occurs.
D. Diplotene- Homologous chromosomes move slightly appart.
E. Diakinesis- Homologous pairs move to the equatorial plate.
45
What happens after prophase of meiosis 1?
Prometaphase
| - nuclear membrane breaks down
46
What happens in metaphase of meiosis 1?
Homologous pairs are now all lined up on the equatorial plate.
47
What happens during anaphase of meiosis 1?
Homologous chromosomes seporate, so that each daughter nucleus is now haploid (unlike in mitosis where sister chormatids separate the daughters are diploid).
48
What happens in telophase of meiosis 1?
Events of prometaphase are reversed and nuclear envelope reforms.
49
What happens in meiosis II?
M1 produces 2 daughter cells ( the two n, 2C cells)
Both of these cells undergo meiosis II.
Basically just like meiosis the sister chromatids seporate to give a total of 4 gametes.
50
What happens if two different gene loci are on the same chromosome?
And are filled by two particular alleles then those alleles will be inherited together. This is known as linkage.
51
When an experiment was carried out into linkage, the results produced a 10:2:2:2 ratio, what was the reason for this?
The result sits half way between mono/di hybrid crosses. (Half between independent and complete linkage)
- they proposed that although the genes were found on the same chromosome one or both of these alleles sometimes crossed over.
52
What is genetic mapping?
The likes hood of crossover between any two genes gives some idea of how far apart they are.
53
What was Morgan's and Sturtevants 'stroke of genius' regarding the didstance between 2 genes on a chromosome?
- they suggested that alleles found together on chromosomes were linked but those chromosomes were quite fragile and could break appart. They realised that the further appart any two genes are on a chromosome the more likely they'd be separated by random chromosomal breaks and crossover.
- this meant they could use the frequency of linkage breaking of alleles as an indication of how far those alleles were from one another.
54
What are crossovers?
Recombination between homologous chromosomes in prophase I.
| - they occur when homologous pairs line up (synapsis) during zygotene.
55
How do crossovers occur?
When they're sitting close together the double helix that makes up one sister chromatid in one homologous chromosome, can UNWIND AND INVADE the double helix that makes up the sister chormatid in the other homologous chromosome, this forms a holiday junction.
- cutting of the holiday junction results in 1 of 2 things:
> non crossover products
> recombination that leads to crossover products, therefore generate new combinations of alleles.
56
SEE diagram on page 7
3/9 section Bothwell
57
Explain how Mendelian genetics gives us a 'null hypothesis'
Gives us a model we can use to redact how information is passed from parents to offspring; it allows testable predictions to be made about how many offspring will have XYZ phenotype based on a number of assumptions.
- we can then compare those predictions with observations- if the predictions aren't met, then we need to reconsider our assumptions.
58
What 3 assumptions are made by the Mendelian model?
I. Genes are on nuclear chromosomes
II. Only one gene locus determines a trait
III. Alleles are either dominant or recessive.
59
How is number III of Mendelains assumptions flouted in nature?
( alleles are either dominant or recessive)
Alleles can have a wide range of effects; they can be incompletely dominant, co-dominant or they can show varying degrees of expressivity.
60
How is number II of Mendelains assumptions flouted in nature?
( Only one gene locus determines a trait)
More than one gene can be involved; this is called gene interaction.
61
How is number I of Mendelains assumptions flouted in nature?
( Genes are on nuclear chromosomes.)
Sometimes a trait isn't determined by nuclear DNA sequence.
A. If it's determined by extra unclear DNA (I.e. Mitochondrial or chloroplast)
B. If it's determined by something other than the DNA sequence (this is epigenetics)
62
What actually is an allele why do they play such a huge part in inheritance?
An allele is a DNA sequence that codes for a protein.
- different alleles have slightly different sequence therefore produce slightly different proteins.
- sometimes an allele will procedure a protein that doesn't work (= a loss unction mutation) or a protein that does something novel (= a gain function mutation).
- because most genes are large this means that any gene has a large number of possible alleles.
63
What is incomplete dominance?
In some, slightly unusual case, phenotype is determined by a blend of the products of different alleles; the best studied case is probably flower colour in snapdragons, in which the pigments produced by different alleles 'blend' together.
64
What is co-dominance?
More common than incomplete dominance, alleles produce products that are co-expressed; the best known example is blood groups.
65
Explain co-dominance in relation to blood groups.
Blood cells express a surface antigen that's determined by the genotype at the I locus; alleles can be A, B or O.
The Ia Ib genotype give both A and B antigens, and an AB phenotype.
- this isn't a blending as with incomplete dominance it's a dual phenotype.
66
What is lethality?
It is a reality let common complication to Mendal's ratios occurring when the homozygous recessive just isn't variable, it's said to be 'lethal' a famous example is the Agouti gene in mice.
67
What does the Agouti gene in mice do?
| What are the 2 alleles?
Determines coat colour.
A is the recessive agouti allele and homozygous are brown
Ay is the yellow allele and is dominant for yellow coat colour.
BUT the AyAy is lethal and the embryo doesn't develop properly.
Therefore the Ay allele is dominant for one thing (coat colour) but recessive for another (embryonic development).
68
What is so lethal about hyper-yellow fur?
Turns out to be an example of linkage.
- the Ay allele contains a deletion in the Agouti gene, and this deletion also knocks out the gene next to it, which IS involved in embryonic development.
69
What is genetic interaction?
When more than one gene is involved.
- many traits are determined by more than one gene, often because several genes take part in the metabolic pathway that determines phenotype.
70
What is Epistasis?
When 2 genes work together
71
If we do a cross of IaIb, Hh X IaIb, Hb (aka F1 generation are all heterozygous for blood group and H factor synthesis) the F2 generation segregates in units of 1/16 but not 9:3:3:1 why?
We're only meeting the phenotype of one trait with co-dominant alleles (blood group) so we'd expect a 1:2:1:0 ratio of A:AB:B:O if the I locus was the only one responsible.
In stead we get 3:6:3:0.
It turns out the hh homozygous are O even though their blood group genotypes are IAIA, IBIB, or IAIB.
72
Why do we use complimentation?
Because genes can have multiple alleles, because different alleles can produce similar phenotypes, and because some phenotypes are the result of multiple gene interactions, it's often quite hard to tell whether two mutants that produce the same phenotype are:
I. mutants in the same gene (I.e. They're different alleles, each giving a similar phenotype:
II. Mutants in different, epistatic, genes.
To distinguish between these 2 possibilities we carry out complementation tests.
73
How can we use complimentation to find out whether the mutations are in the same gene? (Imagine we have 2 mutants, a and b, each of which have short wings).
We cross pure-breeds of each mutant.
74
Once crossed with pure breeds if the a and b mutations are in different genes what happens?
The offspring inherits one working copy of each gene, so the normal phenotype is restored and the genes are said to 'complement' each other.
75
Once crossed with pure breeds if the a and b mutations are in the same genes what happens?
the offspring inherits 2 broken copies of the gene (each broken at a different sport, but both still broken), so retains the mutant phenotype.
76
What is Extranuclear (aka uniparental or cytoplasmic) inheritance?
Not all genes are in the nucleus and on nuclear chromosomes; ,mitochondria and chloroplasts have their own genomes and occasionally, mutations in these can cause trouble.
77
What usually results from mitochondrially-determined traits?
Because mitochondria are involved in energy generation, mitochondrial mutants often cause phenotypes with diseases of energy generation (e.g. MERRF).
- Mitochondria are inherited through the mother, so that skews the inheritance pattern.
78
Explain the principles of chloroplast inheratance?
| mention Carl Correns discovery
The classic example is leaf colour in the 4 o'clock plant, discovered by Carl Correns in the early 20th century.
- Leaf colour in these plants is determined by chlorophyll content, which is determined by a gene in the chloroplast genome.
Because plant embryos get their cytoplasm from their mothers leaf colour is inherited from the mother rather than the father.
79
Are genes the only things that determine phenotypes?
- it is not strictly speaking genes that determine phenotypes, but instead gene expression.
. This can be effected in a number of ways.
80
What other 2 phenomena must we consider when thinking about how genotypes are determined?
I. Epigenetics
| II. Environment
81
What is the concept behind Epigenitics?
Either DNA or the histones its wrapped around can be 'tagged' with small molecular groups; (common on histones = acetyl group) ( common on DNA is methyl groups).
- these tags act as switches to turn genes on or off- if DNA is methylated, it's genes are less likely to be expressed.
- these 'tags' can also be passed from parents to offspring.
>>>> so they're HERITABLE but NOT DNA.
82
In what way is the Agouti gene effected by epigenetics?
The A gene is recessive partly because it's got an Epigenitic tag on it (I.e. The DNA is methylated). In some circumstances, that tag can be removed.
83
What is interesting about the Agouti genes associated epigenetic tag?
1. The tag can be passed from the F2 generation to its offspring but whether or not the tag is removed can depend on whether the chromosome that it's on is being packed into the sperm or eggs.
- this means you can get inheritance patterns that look like the uniparental ones. The maternal allele can have a tag; while the paternal one goes without or vice versa.
2. many of the Epigenitic tags are reset during meiosis in response to the cells environment. They are reset when the germ cells are produced and fuse to form an embryo.
- this means that the health of the mother or father at the exact time they proud ice their gametes can, in theory, have long lasting effects o not he phenotype of their offspring.
84
What are some finding of epigenetics in humans?
- observations suggests that some Epigenitic tags can be passed down several generations.
- the famous Overkalix study showed the health of individuals could be affected in parts by what their grandparents ate.
- many human diseases e.g. Cancer, diabetes and obesity involve the epigenome.
85
How can environmental factors play a part in genetics?
Environmental effects act to increase the variability of the phenotype produced by a genotype.
86
Why do continuous traits pose a problem?
Traits such as height, weight are even more difficult to discect into genetic and environmental determinants.
87
What is the multiple gene hypothesis? Explain the term 'additive'
Suppose multiple genes exist, and suppose that each of these genes have 2 alleles, one increases the amount of a trait and the other has an opposite effect.
- the final trait will then be given by the sum of all these alleles of different genes ( we say the genes are additive).
88
As the number of contributing genes increases how does the distribution change?
Distribution looks more and more normal.
89
If we have a trait with a continuous phenotype, how can we tell the difference between:
A) no genetic influence, lots of enviro entail influcence
B) lots of genetic influence little environmental influence
The early exponents of modern synthesis reasoned the following:
1. If variation of phenotype depended on ENVIROMENTAL factors, then the range of phenotypes that would be seen in the offspring of any 2 individuals would be the same range seen in the original group and wouldn't depend on which 2 individuals you picked as the parents.
2. On the other hand, if the observed variation in phenotype depended mainly on genetic factors, then the range of phenotypes that would be seen in the offspring would depend exactly on which parents you picked.
90
What is Heritability?
The proportion of phenotype variation that is due to genetic variation.
91
How can heritability be calculated?
Plot the phenotype of offspring against mean parental phenotype (I.e. Plot your height against average height of your parents); the heritability (=h^2) of the trait is then given by the slope of the regression fit.
92
What can estimates of heritability show you?
Whether you should be looking for a 'gene responsible'
| Or focusing on environmental factors.
93
Why is estimating heritability big business in animal and plant breading?
High heritability drives selective breeding for crop or animal improvement.
- in humans heritability is often estimated using identical twins.
94
What had the advent of Next generation DNA sequencing (NGS) helped?
It has made it cheaper and easier to carry out Genome-Wide association studies which attempt to link particular regions of DNA with particular traits in large populations.
95
What is Aneuploidy?
Where organisms gain or loose individual chromosomes, or large chunks of them.
96
What is Polyploidy?
Where organisms gain another copy of their entire genome (lots of chromosomes).
97
What does Aneuploidy usually result from?
Usually through chromosome non-disjunction during either Meiosis I or Meiosis II.
Animals don't usually support Aneuploidy that well and its associated with a number of developmental conditions.
98
How can Aneuploidy be sub-divided by?
The number or chromosomes lost/gained.
99
What is: monosomy?
Loss of one individual chromosome (e.g. The Y chromosome.) or part of one chromosomes.
100
What is: trisomy?
Gain of one individual chromosome
101
What is: tetrasomy, pentasomy and so on?
Gain of 2,3 etc individual chromosomes.
102
Look at page 2. Bothwell 6/9 to see how the different aneuploidies are formed.
Wnwjn
103
Why are aneuploidies so damaging?
- Humans in particular are v sensitive to genome loss; losses or gains of only 1-5% of your genome can have highly deleterious effects.
- most expalinations of this invoke gene dosage - which is the idea that gene expression is balanced across a pair of homologous chromosomes.
> if chromosome numbers aren't quite right then gene expression will be out of balance, producing deleterious effects.
104
What are aneuploidies thought to be responsible for in Humans?
Estimated to be responsible for around 20-50% of spontaneous abortions.
105
Why are plants thought to be more tolerant to aneuploidies?
Possibly because their developmental pathways are much more plastic and less closely tied to their genomes.
- the textbook example is thorn Apple.
> this has 12 pairs of chromosome, and a characteristic trisomy can variety exists for each chromosome.
106
How are 97% of Down's syndrome cases caused?
Spontaneous aneuploidies when meiosis goes wrong.
107
Explain inheritance of Down's syndrome using the 2 different pathways that the t(14,21) can go at meiosis.
I) can go on its own. M2 will produce 50/50 gametes with the following features:
- gametes with one copy of 14 and one 21 (I.e normal)
- gametes with one copy of 14fused21 i.e normal phenotype- all DNA there in right order but Down's carrier.
2) can go with one of the other chromosomes
- Monosomic
, gametes with one copy of 14 but no 21; these lack a complete genome and die.
- Trisomic
- gametes with one copy of 14 but 2 copies of 21 therefore inherited Down's.
108
How is polyploidy formed?
If the whole genome is duplicated, the resulting organism is said to be polyploid. This is rare in animals but reasonably common in plants.
109
What is the big problem faced by organisms with polyploidy?
Getting through meiosis.
- during the most important phase of meiosis, homologous chromosomes need to segregate correctly, otherwise few viable gametes will be produced and the polyploids will be sterile.
Auto/Allo ploids face different problems getting their chromosomes to segregate during meiosis.
110
What is autopolyploidy
= Multiple sets from the same species or individuals.
- they have too many homologous chromosomes.
- so instead of 2 chromosomes pairing up at meiosis they get what is known as multivalents.
111
How does Autopolyploidy effect segregation?
The multiple homologous chromosomes (multivalents) create a jumble at the spindle that can be hard for the cell to untangle.
- this is especially a problem for non-even polyploids odd numbers when divided by 2 leave a remainder.
112
What is allopolyploidy, this explanation will need to include their formation as this effects how problems at meiosis are caused.
Allopolyploid formation often starts when 2 gametes, from different species, fuse to form a hybrid zygote.
- such inter-specific hybridisation happens in animals, but the chromosomes from each parent aren't similar enough to form homologous pairs at meiosis, which means that chromosome segregation into gametes end up being essentially random.
- given how many chromosomes there are, the chances of getting a full set in any one gamete are pretty low. So, animal hybrids of this sort can grow (by somatic cell mitosis) but they can't produce gametes and so are sterile.
113
How can plants overcome the problems associated with allopolyploidity with somatic doubling?
- basically the s phase without cell division afterwards.
114
Summarise somatic doubling with regards to the domestication of wheat bread example.
I. Gametes from two species form hybrid, diploid zygotes but these wouldn't be able to produce viable gametes because the chromosomes aren't closely related enough to form homologous pairs during meiosis.
II. The hybrid, diploid zygotes undergo somatic doubling (= all the chromosomes replicate at S phase, but the cell doesn't divide).
This leads to hybrid tetraploid (2n X 2 = 4n) zygote but now each chromosome has a homologue. (=its own copy produced during the somatic doubling) so the zygote can grow up into a plant that can undergo meiosis and produce gametes.
115
What are the advantages of polyploidy?
1. Allows genes to be brought in from closely related species (though hybridisation) which can broaden the gene pool.
2. Allows extreamly rapid speciation which may allow the plants to expand into other ecological niches.
3. Can often have more gene product per cell then diploid relatives, can make them more productive.
4. Having more copies of a gene in a cell can allow some copies to change providing the raw material for evolution; evidence that vertebrates evolved from a polyploid ancestor.
116
What are the 2 main theories for meiosis (sex) as the reason for non-self fertilisation?
I. Leigh Van Valens red queen hypothesis
| II. Mullers ratchet
117
How is sex specified environmentally? Can give example
Sex of crocodile babies depends on the temp at which the eggs are incubated over the middle of their gestation. If between 31-34 will be male
118
How is sex specified genptypically?
There can be genes responsible for sex determination.
- they've evolved from autosomal independently in a number of animals and plant lineages and still carry a number of other, non-sex-determine genes.
119
Why don't we sometimes get XY females?
The reason is that the X and Y chromosomes unlike all the autosomal don't form crossover products with each other.
- recombination is supressed in the Y chromosome.
- the reasons for this are subtle- the Y chromosome doesn't code for genes as much as it codes for a difference (between 2 sexes); there's no evolutionary advantage to mixing X and Y though recombination, as the difference might be perturbed.
120
What is meant by the lack of degeneracy of the Y?
No recombination occurs on the Y. So the Y chromosome has accumulated mutations that have knocked out most of its genes and turned them into pseudogens. We say that it's 'degenerate' and it will one day be replaced.
121
What are the three possible reasons that allow females to make twice the gene product?
I. Could run both X chromosomes at half the power. (This happens in female C.elegans)
II. Could hyper activate the X chromosome in males, so that it produces as much gene product as the two X chromosomes in females.
III. Could shut down one of the X chromosomes in females (this is what happens in mammals). One X chromosome is turned off and called 'Barr body'.
- X inactivation happens to one chromosome per cell at random in early development. The inactivated X chromosome expresses one gene called Xist, which shuts down the rest of the chromosome by converting it into heterochromatin.
122
What happens in mammalian embryos about 12 days after conception?
In each cell one X chromosome at ransom is inactivated, so that mamillian females become mosaics.
123
What causes the coat colour change?
The gene for cat coat colour is on the X chromosome:
- O allele = reddish colour.
- o allele = brownish colour.
So if the cat is heterozygous at the gene colour, then the mosaic nature of the X inactivation will mean that 100-ish cells in the embryos at the time of X inactivation will grow up into 'patches' in the adult cat.
- Each patch will have one or the other chromosome active, and so one or the other colour is expressed, hence the patchiness.
- there is also another gene that is sometimes expressed that produces white.
124
What is the difference between genetic and genomics?
```
Genetics = the study of how a few genes determine a phenotype.
Genomics = the study of how lots of genes and their architecture determine phenotype.
```
125
What is G banding used for today?
Diagnosis of chromosomal abnormalities.
126
What is thought to have caused 'Junk DNA'
Genetic drift rather than natural selection.
127
What were the 4 main aims of the human genome project?
1. To physical map of the human genome (G banding in situ hybridisation)
2. A genetic map of the human genome (genes,polymorphism)
3. The nucleotide sequence of the human genome.
4. Free public access to all the data generated.
128
What is the idea behind 'sequencing-by-synthesis' ?
Allows the DNA to keep extending rather than stopping to read the fragments, this really speeds it up.
129
How is sequencing by synthesis done?
Each DNA template is exposed to one nt per sequencing round.
- PPi is released when DNA pol incorporates a nt.
- PPi reacts with sulphate adenyl transferase to generate ATP, ATP acts as a substrate for luciferase to generate light.
- Apyrase is then added to break down unreacted nt and PPi, the whole thing is washed and stated over.
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What is bioinformatics?
The analysis of genome sequencing normally in stages.
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What is base calling and how is it done?
It is the quality of the read being assessed.
- the industry standard for doing this is Phred, which gives quality scores. These QS get progressively worse as we go along a read and once they drop below a certain value, we chuck the rest of the read.
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What is draft assembly?
Once we've selected the 'good' reads we then assemble them into contiguous (= using computers as per shotgun sequencing).
- then we assemble reads into contiguous and supercontigs and, ideally, asign these to linkage groups or a genetic map.
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Next we can feed the sequence into various pipelines which ask 2 types of questions, what are they?
1. Where are the coding regions (CDS)?
| 2. Where are the regulatory elements?
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How are the CDS found?
A. First CDS tend to show some degree of conservation. So if a region of DNA in one genome looks like a region of DNA in another, then it might be a CDS. We look for simmialriteis using BLAST>
B. Second, proteins are usually constructed as molecules. So we can feed a sequence into a protein prediction database to see whether it contains any known structural motifs.
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How can the regualtory elements be found?
This is a bit harder and in many ways is the focus of the ENCODE consortium, which aims to identify all functional regions in the human genome, ENCODE is ongoing and there's much heat and perhaps less light at the moment.
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Why do we sometimes also need to use expert annotation?
BLAST tools are very fast but not that accurate. So can't always trust their results. Must draw proper phylogenetic trees to distinguish orthologs.
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Expalination the formation of the 3 corn kernels colours.
- dominant C allele gives blue/purple colour. Recessive c allele (un-pigmented but ends up looking yellow)
- blue allele can mutate to give yellow allele and sometimes these yellow alleles will mutate back to give blue flecks.
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What is the 'breakage-fusion-bridge' mechanism?
Some corn chromosomes brake easier than others.
- McClintock was able to develop this into a way of nibbling bits from the ends of target chromosomes. She could remove some alleles and study their effect.
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What was the proposed Ac/Ds/C system for corn kernel colour?
BFB system allowed Mclintock to investigate which genes helped the C gene. BY Nibbling bits off the p arm of the chromosome 9, she showed that part of it was needed to make the yellow 'mutant' unstable, and she proposed that the p arm contained a gene that 'activated' instability which she called the Ac gene (activator gene).
she then identified another gene that was needed to give the unstable yellow mutants. This gene was associated with a slight weird phenotype that gave characteristic beaks in chromosomes was called the D (dissociatior) chromosome.
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What was her so not big failure in genetic mapping?
She was unable to map the D genes location. BUT she realised that linkage mapping concept was dependant on genes remaining in the same place. She realised her results could be explained if genes JUMPED around.
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What were her specific proposals about genes JUMING?
She proposed that if Ds gene moved into the C allele then it would turn it off (and the kernel would change from blue to yellow).
- I'd the Ds elements were to move agin during a later stage of mitosis back out of the C allele then the daughter cells would switch back to being blue again this would explain the freckling pattern seen.
- in fact the number and size of blue speckles can tell us the frequency and timing of transposition events. Larger = earlier transposition.
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What are class 1 and class 2 transposons?
Class 1 = move using RNA intermediates
| Class 2 = move using DNA intermediates.
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How do class 2 transposons move?
Some transpons actually physically move: the DNA that codes for them is cut out of the genome and moves somewhere else.
- mechanism is pretty simple and is often referred to as 'cut and paste'.
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What enzyme catalysts the 'cut and paste' activity of class 2 transposons?
Transposase
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List the 5 steps involved in class 2 transposons?
1. Transposases recognise, and bind to, each inverted repeats.
2. The transposases then also bind to each others to make a loop out of the transposon
3. The tranposase makes a staggered cut.
4. And then inserts the transposon
5. The caps are filled to leave direct repeats (I.e. Read in the same direction).
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How do reverse transposases move?
Movement is mediated by an RNA intermediate.
- Transposon is first transcribed (usually RNA pol II) to give an RNA transcript, and that transcript is then reverse transcribed (by an enzyme called Reverse transcriptase) to give an RNA sequence that's then insertd back into the genome somewhere else.
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What are LTR retrotransposons?
Usually sever 100 nt sequences that contain various signals for the targeting and movement of transposons.
- the best studied examples of LTR retrotransposons are probably the Ty elements of yeast, which have been adapted into a transformation system and the Human Endogenous Retro virus.
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What are Non-LTR retrotransposons?
Don't always need LTRs to identify where TEs are sitting, Many TEs make do with much shorter sequences called Target Site DUplications (TSDs), which are 10-20nt long.
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What are 2 common non-LTR retrotransposons?
1. Long interspersed Nuclear Elements (LINEs): these are relatively long (a few Ib), have TSDs at each end, and are often autonomous, encoding their own reverse transcriptase. An important example in humans is the L1 transposon.
2. Short interspersed Nuclear elements (SINEs): again these have TSDs at each end, but this time are much shorter (a few hundred bp) because they don't contain any coding regions (and hence are non-autonomous). The Alu element that we saw previously is an example of SINE.
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What does it mean by the silencing of transposons?
- there are a lot of potential transposons in our genome, there are few actual transposons because most of them are silenced in a variety of ways.
- we've already come across epigenetic silencing (e.g. DNA methylation) and many transposons in our genome are methylated in exactly this fashion. There's also a lot of evidence to suggest that other silencing methods most notably RNA silencing, act to suppress transposon expression.
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How can transposon movement cause mutation?
- despite all the silencing transposons can be active in our genomes.
- the most visible effect of transposon activation is when a gene ends up getting knocked out, or mutated,where an transposon gets inserted into tit, and this sort of de novo insert action (particularly by L1 transposons) has been observed to cause disease in a number of cases.
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How might transposon movement confer evolvability?
Transposons carry bits of the genome with them when they move, causing exon shuffling and the rapid creation of new proteins;
- if the transposases bind to IR from different TEs, then the loop that gets cut out can contain exons.
Genetics
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