Genetics S1 Y1 Flashcards
1
Q
How is the bacterial genome replicated?
A
Plasmid replication - replication begins at the origin of replication and the strands separate and replicate until two daughter plasmids separate (made up of a new and old strand)
2
Q
2 characteristics of plasmids that make them useful
A
- Used for adaptation (not essential for life though.
- Promote genetic exchange or encode genes to kill other bacteria
3
Q
What enzyme is used to break the double helix structure of DNA?
Why is it used?
A
-Topoisomerase ii
-Used to supercoil the DNA to reduce the space it takes up
4
Q
How is the genome structured in eukaryotes?
How was this discovered?
A
-In nucleus, arranged into linear chromosomes that are comprised of chromatin condensed with histones. The chromosomes have many origins of replication.
-Giemsa patterning
5
Q
Levels of structure to form a chromatid?
A
DNA associated with histones (condense + support) to form nucleosomes which fold to form a chromatin fibre which is coiled and condensed to form a chromatid
6
Q
Why are mitochondria and chloroplasts different to other organelles?
A
-They were both engulfed via endocytosis and were eubacteria before they became associated with eucarya.
-They exchanged genetic material with the nucleus - now depend on nuclear transcription e.g. the proteins in mitochondria are encoded in the nucleus and must be translated and taken up by the mitochondria
-They have much smaller genomes as most of their genome has migrated to the host nuclei
7
Q
-What were chloroplasts and mitochondria before they they became symbionts (closely evolved association via endosymbiosis)?
-Which parent are they inherited from?
A
-Chloroplasts = cyanobacteria
Mitochondria = proteobacteria
- Female parent
8
Q
What are the genes in mitochondria for? (4)
A
- Respiration and oxidative phosphorylation
- Transcription and translation
- RNA processing
- Importing proteins into cell
9
Q
Why is the mitochondrial genome shorter than the normal genome?
A
Contains fewer genes, has no introns, only one promoter per strand, 2 strands
10
Q
Why are diseases associated with mitochondrial mutations complex?
A
Mitochondria segregate randomly during cell division, so random daughter cells will contain mutated mitochondria. Even if a mother shows no signs of mitochondrial disease, she may produce diseased gametes that means her offspring may get symptoms of mitochondrial disease
11
Q
What is variation in mitochondrial DNA called?
A
Heteroplasmy
12
Q
How is it possible that embryonic stem cells with the same genome can be differentiated to form many types of cell?
A
Differential gene expression (different genes are expressed)
13
Q
What is the promoter region used for?
A
To initiate transcription (where transcription factors and relevant proteins such as DNA pol. bind)
14
Q
6 stages of gene expression regulation?
A
Chromatin –> transcription –> RNA processing –> RNA stability –> translation –> posttranslational modification
15
Q
- Why must chromatin condensation vary?
- How does it vary?
A
- Must be less condense when transcription is occurring so proteins can access it
- Histone tail methylation and acetylation, DNA methylation
16
Q
What does DNA methylation cause?
A
Changes chromatin structure, nucleosome positioning and modifies histones
17
Q
What is the effect of heavy DNA methylation (especially on CpG islands)?
A
It prevents transcription (and silences corresponding genes when CpG islands are methylated)
18
Q
How is the issue of 2 copies of the X chromosome dealt with in females?
A
One X chromosome is inactivated through engulfing by RNA to change the chromatin structure
19
Q
How are transcription factors involved in transcription?
A
Two main types are repressors and activators:
- Repressors bind to promoter region and inhibit translation
-Activators bind to enhancer regions and increase rate of transcription
20
Q
How do all genomes in all organisms relate?
A
All have ROUGHLY the same number of exons (individual of their size)
21
Q
What organism has the largest genome?
A
Protozoa
22
Q
What is the C-value paradox?
A
Term given for the lack of a link between an organism’s complexity and the size of its genome
23
Q
2 reasons why eukaryotic genomes vary in size?
A
- Polyploid chromosomes
- Levels of introns vary
24
Q
2 things repeated sequences in a genome can be?
A
Dispersed or tandem (clustered)
25
What are transposable elements?
Sequences that can replicate and insert into new positions - this can restore normal function of a gene but it can reinsert somewhere where another gene's function is disrupted
26
What is the difference between negative and positive supercoils?
Negative = underwinding (less tight) - MORE COMMON IN EUKARYOTES
Positive = overwinding (more tight)
27
What do supercoils in bacterial DNA form?
A nucleoid
28
Which eukaryotic cells do not have mitochondria and why?
Those that live in anaerobic environments (have hydrogenosomes instead)
29
2 hypotheses for the origin of eukaryotic cells?
1. Evolved from ancestral archaeon that later incorporated the proteobacterium (mitochondria)
2. Evolved from symbiosis of archaeon and proteobacterium (mitochondria)
30
3 ways some genes are regulated by RNA degradation?
1. 5' cap removed (prevents initiation of translation)
2. poly (A) tail shortened
3. Degradation of 5' UTR, coding sequence and 3' UTR
31
What is the poly (A) tail for and what does it enhance?
- They act as cap-binding proteins and prevent degradation
- They enhance binding of the 5' end of mRNA to the ribosome
32
2 ways RNA is modified to make proteins for diverse?
1. Alternative splicing (removal of some exons and occasionally introns so one gene can produce many products)
2. RNA editing (modifies nucleotides to change protein)
33
3 ways RNA interference is used to regulate genes?
1. Translation inhibition (via small and microRNAs e.g. by methylating DNA or histones or degradation)
2. Transcriptional silencing (by changing chromatin)
3. Lowering gene expression and degradation by siRNAs
34
How do siRNAs and miRNAs prevent translation?
Form DNA hairpin and then enzymes cleave the stem to form double-stranded fragments - one of these strands of RNA enters RNA-induced silencing complex (RISC) to result in degradation and inhibited translation
35
2 types of transcriptional regulation?
1. Positive regulation - activator binds to DNA near gene to allow transcription (RNA polymerase can bind to promoter)
2. Negative regulation - repressor binds to DNA near gene to inhibit transcription (RNA pol. cannot bind to promoter)
36
How do activators work?
Bind to enhancer region and cause an allosteric change in DNA so RNA pol. can bind
37
- How do repressors work?
- How does an inducer affect this process?
- Bind to operator and cause allosteric change so RNA pol. cannot bind
- They allow transcription as they bind to repressors and change their structure so they cannot bind
38
What is an operon?
Cluster of structural genes and sequences that control transcription that are transcribed together
39
Lac operon:
- What is produced to break down lactose?
- How is it ensured that the enzyme is not synthesised when lactose is not present?
- How does this change when lactose is present?
- Beta-galactosidase
- Repressor coded for by lacI is bound to operator so lacZ (B-galactosidase) and lacY (lactose permease) cannot be expressed
- Inducer called allolactose binds to repressor so RNA pol. can bind and express the enzymes to allow for lactose digestion
40
Lac operon:
- What is constitutive expression?
- What happens when glucose levels are low in some bacteria?
- Mutation where lacZ and lacY are always expressed
- [CRP-cAMP] increases which induces positive regulation so lactose is digested for energy
41
Regulatatory transcription factors:
- What are their 2 binding sites?
- Enhancer on DNA and other to recruit general transcription factors (activators and promoters) which are assembled near TATA box in promoter
42
What do general transcription factors do? (2)
1. Attract RNA pol.
2. Bind to silencers and repress transcription
43
What enzyme removes introns and binds exons?
Spliceosomes
44
What is the purpose of postranslational modification?
Regulates structure and function - can change conformation to activate/inactivate a protein
45
What does methylation of cytosines on CpG islands cause?
Heavy methylation = no transcription
- this can be as a response to environmental signals
46
What does epigenetics change?
The way DNA is packaged which affects gene expression
47
What is an example of gene expression occurring on a chromosomal level?
One X chromosome out of the two in females is inactivated by becoming covered in Xist RNA from the X-chromosome inactivation centre
48
What happens to transcription when antisense RNA binds to some bacterial genes?
Prevents it
49
What are riboswitches?
Regulatatory sequences of mRNA that bind to ribosomes and change secondary structure which alters gene expression as translation cannot occur
50
2 players of human genome project?
1. Public effort, international spread of chunks of genome and stored in yeast mini-chromosomes
2. Celera genomics (private) - whole genome shotgun strategy
51
6 steps of public human genome sequencing strategy?
1. DNA is partially digested and overlapping fragments are cloned in bacteria
2. Large-insert clones analysed for markers or overlapping restriction sites
3. Allows large-insert clones to be assembled into a contig (continuous DNA stretch)
4. Subset of overlapping clones that cover entire chromosome are selected and fractured and cloned
5. Small-insert clones sequenced and overlaps in these are used to assemble them in the right order
6. Final sequence made by putting sequences of large clones together
52
How does whole genome shotgun sequencing work?
Small-insert clones are prepared directly from genomic DNA and are sequenced in an automated way
53
3 subsections of genomics?
Structural
Comparative
Functional
54
Structural genomics:
- What is the genome made up of?
Tandem repeats (highly conserved), transposable elements (can change position on genome), heterochromatin (condensed DNA) and non-conserved sections
55
Comparative genomics:
- Purpose?
- 3 sections of predicting function from sequence?
- Compares genomes to understand gene and species evolution, identify conserved and functional areas, finding how species relate and the function of genes
- Homologous, orthologs, paralogs
56
What is meant by homologous?
Evolutionary related genes
57
What are orthologs?
Homologous genes in different species from the same gene in a common ancestor
58
What are paralogs?
Homologous genes from duplication of a gene in the same organism
59
Comparative genomics:
- How can specific phenotypes be identified as having a role in evolution?
- What does it mean when genes show low rates of evolution?
- Genes that show accelerated evolution in evolution in lineages with specific phenotype
- Probably have a key function
60
Functional genomics:
- What does it determine?
- What is the transcriptome?
- What is a proteome?
- Gene function
- All RNA molecules transcribed from genome
- All proteins encoded by genome
61
Functional genomics:
- What is transcriptomics?
- 2 ways of doing it?
- Assessment of gene activity of many genes at a time
- 1. Microarrays (nucleic acid hybridisation, known DNA fragment used as probe to find complimentary sequence)
2. Next generation sequencing (RNA fragments sequenced then annotated by aligning them to a reference genome sequence)
62
What is cell division for?
Growth, cell replacement, healing and reproduction
63
How is bacterial genome organised?
Highly expressed genes near origin of replication and genes with similar functions are clustered together
64
Purpose of meiosis, meiosis I and meiosis II?
Meiosis = produces haploid gametes
Meiosis I = separation of homologous chromosome pairs
Meiosis II = separation of sister chromatids
65
3 causes of variation?
Crossing over, independent segregation and fertilisation
66
How do prokaryotic cells divide?
Binary fission (intitiated at origin of replication):
1. 2 plasimids form (each bound to different part of membrane)
2. Cell elongates and plasmids separate
3. Constriction at midpoint and division
67
4 parts of interphase in eukaryotes?
G1 phase = prep for DNA synthesis
S phase = synthesis of DNA
G2 phase = prep for mitosis, increase in size
G0 phase = nondividing
68
What does karyotype mean?
Number and shapes of chromosomes in a species
69
Phases of mitosis and meiosis are in week 5 reading
Prophase, prometaphase, metaphase, anaphase, telophase, prophase I, prometaphase I, metaphase I, anaphase I, telophase I etc
70
How does cytokinesis work?
Actin filaments form a contractile ring and the cytoplasm is pinched (animals)
In plants a phragmoplast is formed to form the cell wall
71
What do cyclin-CDK (cyclin dependent kinases) complexes control?
- Passage through the cell cycle (known as proteins seem to appear and disappear in cell cycle as they are activated and inactivated) --- CDKs are only active when bound to cyclin
- They bind to a target protein and phosphorylate it to promote cell division and activate transcription factors in S phase
72
Role of cyclin B-CDK?
Prepares cell for mitosis
73
Role of cyclin D and E-CDK?
Prepare cell for DNA synthesis
74
Role of cyclin A-CDK?
Initiates DNA synthesis and prevents DNA replicating more than once in a cycle
75
3 checkpoints in cell cycle?
1. Spindle assembly checkpoint (checks if chromosomes are attached to spindle)
2. DNA damage checkpoint (checks if DNA is damaged)
3. DNA replication checkpoint (checks if all DNA is replicated)
76
How is a tumour suppressed if DNA is damaged by radiation?
Protein kinase activated which phosphorylates p53 protein which acts as a tumour supressor by binding to DNA and turning on genes such as one to prevent G1 to S transition so DNA can be repaired (BUT p53 exposure over a long period increases Bax gene = apoptosis)
77
Why can cancer come from mutations in genes that control cell division?
1. Loss of checks = uncontrollable division
2. Proto-oncogenes (altered genes) have cell division role
78
Why is overactivation of one oncogene (possibility to cause cancer if activated) or inactivation of a single tumour suppressor not enough to cause cancer?
Requires greater build-up of mutations
79
How is division of cytoplasm different between sexes for gametes?
All products of meiosis in males become sperm, only one is an egg in females and the other 3 are polar bodies
80
- What is an oncogene?
- Protoncogene?
- A gene that causes cancer if it is mutated
- Mutated gene that causes cancer
81
3 ways mutations can be?
- Deleterious (leads to disease/disorders)
Neutral
Advantageous
82
What is mutagenesis?
Tools to understand genetic and developmental mechanisms
83
What are polymorphisms?
Changes in nucleotide sequence
84
How were mutations seen to arise?
Bacteria were plated, then half were picked up with a velvet disc and plated on another plate - one is a control and the other had a selective medium - some colonies lived meaning they were already mutated (did develop from exposure)
85
What are somatic mutations?
Mutations in non-reproductive cells that can cause cancer and are passed on in mitosis but aren't heritable
86
What are germ-line mutations?
Less common mutations in gametes that can be passed onto half of next generation (but plants do not have a segregated germ-line)
87
Why do multiple mutations cause cancer?
Tumour suppressors are deactivated
88
When is the variation of mutation site and generation highest?
In small genomes
89
Why are most new mutations from males?
Sperm mutate much more than eggs as they divide much more
90
3 types of mutations?
1. Substitution of a base (point mutation/SNP)
2. Insertion of bases
3. Deletion of bases
(insertion and deletion = indels or frameshift)
91
Point mutation:
- What causes it?
- 2 types?
- What does it not change?
- Why is location relevant?
- Wobble
- Transition (purine to purine or pyrimidine to pyrimidine) and transversion (purine to pyrimidine or pyrimidine to purine) in 2:1 ratio in rate
- Gene size
- If it occurs in introns there is no effect, if it is in exons there will be predictable consequences
92
Insertion and deletion:
- Why is indel difficult to use?
- What fraction of point mutation rate is the indel rate?
- Does not differentiate between insertions and deletions
- Between 1/10 and 1/20
93
What is the size of the region duplicated or deleted in copy-number variation?
One of more complete genes
94
Why tandem repeats/microsatellites used in forensics?
Change rapidly
95
5 causes of mutations in DNA?
1. Single-stranded break
2. Double-stranded break
3. Missing bases
4. Cross-linked T bases caused by UV radiation
5. Bulky side group attached to a base
96
What is strand slippage?
New strand loops out and a nucleotide is added to new strand, then template strand loops out and one nucleotide is left out from new strand which results in insertions or deletions
97
What does unequal crossing over cause?
One product has insertion, the other has deletion
98
What is repeat expansion?
A special insertion whereby there is an increase in copies of groups of nucleotides
99
What is the mechanism of repeat expansion?
1. DNA has many copies of a triplet
2. Strands separate and replicate
3. Hairpin forms on newly synthesised strand and part of the template will be replicated twice which increases the number of repeats on the new strand
4. Two strands of new DNA separate and the strand with extra CAG copies is the template for replication
5. Resulting DNA has 5 additional copies of CAG repeat
100
4 ways of repairing DNA damage?
1. DNA ligase sealing breakage in sugar backbone (uses ATP to join 3' OH and 5' phosphate)
2. Post-replication mismatch repair (single misplaced base is recognised by Muts proteins is removed and replaced by DNA segment using DNA polymerase, MutL, MutH and exonuclease)
3. Base excision repair (incorrect base and sugar removed by AP endonuclease, and replaced)
4. Nucleotide excision repair (multiple mismatched bases in a region recognised, enzymes to cleave DNA signalled, area of damage removed and replaced)
101
Difference between forward and reverse mutation?
Forward = wild (model) to mutant type
Reverse = mutant to wild type
102
What are:
- Silent/synonymous mutations?
- Missense/non-synonymous mutations?
- Nonsense mutations?
- Codon to synonymous codon
- Amino to different amino acid
- Sense to nonsense (STOP) codon
103
- How do different types of mutations affect fitness?
- Why is not that simple?
- Deleterious = decrease, can be lethal
Advantageous = increase
Neutral = no effect
- Can be dependent on genetic background = epistasis
104
4 types of mutations by phenotypic effect?
1. Loss-of-function mutations
2. Gain-of-function mutations
3. Conditional mutations (effect depends on another factor)
4. Suppressor mutations (hides/suppresses previous mutation)
105
3 types of chromosome mutations?
1. Duplications (most intra-chromosomal)
2. Aneuploidy (1 chromosome has >2 copies)
3. Polyploidy (all chromosomes have 2> copies)
106
- What is tandem duplication?
- Displaced duplication?
- Reverse duplication?
- Duplicated regions are adjacent to one another (special copy-number variation)
- Duplicated regions are separated by a non-duplicated region
- Segment flipped so genes are in opposite order to before
107
Why do duplications affect phenotype?
Unbalanced gene dosage
108
What can deletions cause (2)?
1. Unequal crossing over
2. Loop inpairing
109
What are inversions?
Segments of DNA breaking off and reattaching in the reverse orientation
110
Difference between paracentric and pericentric inversion?
Pericentric affects the centromere, paricentric does not
111
3 effects of inversions?
1. Genes are split
2. Position of genes affected which affects expression
3. Meiosis is disrupted (loops change crossing over products so one has no centromere (this is lost) and the other has two - genes missing from gametes produced
112
What is translocation?
Material moves from one chromosome to another non-homologous chromosome (mostly reciprocal)
113
What is robertsonian translocation?
2 acrocentric chromosomes (1 long arm one side of centromere and 1 short arm the other) do translocation to produce 1 metacentric (normal) chromosome and a small-armed one that is not viable
114
- 4 types of aneuploidy?
- Example?
1. Nullisomy (homologous pair lost, 2n-2)
2. Monosomy (single chromsome lost, 2n-1)
3. Trisomy (single chromosome gained, 2n+1)
4. Tetrasomy (homologous pair gained, 2n+2)
- Down syndrome (91% nondisjunction in maternal meiosis, 7% paternal)
115
3 causes of aneuploidy?
1. Deletion of centromere in mitosis/meiosis
2. Robertsonian translocation
3. Nondisjunction in mitosis/meiosis
116
What is the difference in what is made from nondisjunction in mitosis vs meiosis?
Mitosis = monosomic and trisomic cells
Meiosis = 2 gametes with extra chromsome,
2 gametes without
117
Why are older mothers more likely to produce children with down syndrome?
Higher aneuploidy due to reduced cohesin which means that chromosomes do not always go to right side so they are not divided fairly
118
Why is polyploidy mainly found it plants not animals?
Animals can only develop this if they reproduce parthenogenetically (fertilise themselves) which is unusual
119
Difference between autopolyploidy and allopolyploidy?
Autopolyploidy = all chromosomes from single species
Allopolyploidy = chromosomes from 2 species
120
How can autopolyploidy arise?
Nondisjunction in mitosis to form tetraploid cells if no cell division occurs, if it occurs in germline (meiosis) and diploid gametes form a triploid offspring is made
121
What affects phenotype?
Genotype and environment
122
What factors affect the effect of a mutation?
- If it is homozygous or heterozygous
- Genotype
- Environment
123
What are hotspots?
Sites on genome most prone to mutations
124
3 factors that cause damage to DNA?
1. Radiation
2. Reactive metabolism molecules
3. Environmental chemicals
125
Why is a frameshift mutation so damaging?
Can change ALL the amino acids
126
Why can large-scale mutations be so damaging?
There can be a gain or loss of DNA on the chromosomal level and alter the order of genes
127
Why can deletions persist in a population?
Has another copy in homologous pair
128
How do gene families arise?
Duplication and divergence (which also creates new genes)
129
What is proper gene dosage?
Both parts of reciprocal translocation and one copy of each of the normal homologous chromosomes
130
- What is nondisjunction?
- Difference between first-division and second-division nondisjunction?
- Failure of pair of chromosomes to separate during anaphase
- First-division = homologous chromosomes not separating
Second-division = sister chromatids not separating
131
What are Mendel's 2 laws and the central principle he discovered?
- Law of segregation
- Law of independent assortment
- Principle of dominance
132
What are monohybrid crosses?
Two parents that differ in a single characteristic crossed - led to discovery of dominant/recessive alleles in a 3:1 ratio (AA,Aa,Aa,aa)
133
What are these generations:
- P1?
- F1?
- F2?
- Parental
- First filial (from P1)
- Second filial (from F1)
134
What is inheritance said to be?
Particulate (hereditary elements passed on as discrete units, not a blend of them all)
135
What does the F1 generation have?
Information for both phenotypes
136
What is the law of segregation?
Each diploid organism has 2 alleles for a characteristic which segregate in gamete formation
137
What is a backcross?
F1 crossed with a parent
138
What is a test cross?
Individual with an unknown genotype crossed with an individual with a known homozygous recessive genotype to show if unknown is heterozygous or homozygous
139
What is incomplete dominance?
Both alleles are expressed ( e.g. red and white alleles for flowers make pink flower)
140
What are dihybrid crosses?
2 separate traits, 9:3:3:1 ratio
141
What is independent assortment?
When genes are separated and found of different chromosomes
142
What can genes on the same chromosome be?
Linked (only get parental phenotype) or unlinked (half recombinant progeny, half non-recombinant progeny)
143
Equation for percentage recombination frequency?
recombinant progeny/total progeny x 100
144
6 complications of Mendel's discoveries?
1. Epistasis not taken into account (effect of 1 locus on phenotype depends on genotype of second locus)
2. Penetrance (how many individuals with genotype show phenotype)
3. Expressivity (how variable is the degree/severity of the phenotype)
4. Pedigrees show dom. traits in every generation, recessive are rarer and more likely to skip a generation
5. Most genes are quantitative (few non-disease related)
6. He probably cheated (ignored linkage, results too close to expected)
145
What are B chromosomes?
Chromosomes that act as selfish genetic (transposable) elements that drive through both males and females
146
What kind of inheritance is the inheritance of autosomes?
Biparental
147
What is a common symptom of mitochondrial disease?
Myopathy (neuromuscular disease causing muscle weakness)
148
Difference between homoplasmy and heteroplasmy?
Homoplasmy = all organelles are genetically different
Heteroplasmy = multiple distinct DNA sequences within the cytoplasm
149
Why can a heteroplasmic parent cell form both heteroplasmic and homoplasmic daughter cells?
Mitochondria segregate randomly and independently (replicative segregation)
150
How are cytoplasmically inherited traits inherited from a variegated female?
For example if the female plant was variegated in colour (mix of white and green) then the offspring can be variegated, white or green (usually inherited from mother)
151
What is the genetic maternal effect?
When the phenotype of the offspring is dependent on the maternal phenotype (not their own) EVEN if the maternal genotype is recessive to the fathers - then the F2 generation will return to the dominant trait
152
Why is the mitochondrial genome used to estimate most recent common ancestor?
It is clonally inherited - mutation rate can be used to identify time of most recent common ancestor
153
What is gene conversion?
- Type of homologous recombination whereby genetic material is transferred from donor sequence to homologous acceptor
- There is a double stranded break and strand invasion as crossing over goes wrong during meiosis and either double-stranded break repair occurs or synthesis dependent strand annealing to create mostly non-crossover products
154
What is meiotic drive?
Gametes that are produced have an unequal chance to fertilise due to chromosomal level distortion, death of half the gametes and non-random fertilisation (eggs picking sperm)
155
What are selfish genetic elements?
Nuclear non-mendelian loci that increase in frequency rapidly due to UNFAIR INHERITANCE
156
How do cytoplasmic selfish elements cause female-biased sex ratios?
- Male killing
- Feminisation of males in development
- Parthenogenesis (fertilisation of a female without a male gamete)
157
What are reciprocal crosses?
Crosses where a trait is interchanged between being on female and male parents (dominant trait will be expressed regardless if its from male or female)
158
What is the molecular basis of dominance?
Dominant allele only needs ONE copy to function whereas recessive needs TWO
159
Which trait will reappear in the F2 generation if it was not in the F1 and the progeny were a result of true-breeding strains fertilising one another?
Recessive traits as the F1 generation should solely be dominant
160
Why do gametes only contain one type of allele?
Genes in pairs are segregated in gamete formation if true breeding has occurred and therefore the zygote will be a combination
161
What is incomplete dominance?
Phenotype of heterozygous genotype is intermediate between those of homozygous genotypes (e.g. CrCr and CwCw will make CrCw)
162
What is codominance?
2 alleles producing a characteristic phenotype that can be detected in heterozygous genotypes (e.g. type AB blood)
163
The probability of a genotype's occurrence lies between 0 and 1, how are probabilities of 2 or more outcomes combined (2 rules)?
1. Addition rule - outcomes cannot occur simultaneously as the possibilities are mutually exclusive, so they are added
2. Multiplication rule - outcomes can occur simultaneously as they are independent events, so they are multiplied
RULES CAN BE USED TOGETHER
164
What is the principle of independent assortment?
Segregation of one set of alleles of a gene pair is independent of the segregation of another set of alleles of different gene pair
165
What does independent assortment show?
The random alignment of chromosomes in meiosis as they are randomly pulled to a pole
166
Why do some genes not undergo independent assortment?
If they are linked (genes very close on the chromosome) they will not assort separately
167
How can phenotypic ratios be modified?
By the interactions between genes as some genes can code for proteins in the same biochemical pathway meaning epistasis occurs (phenotypic expression of genotype is affected)
168
What is a pedigree?
Record of ancestral relationships in a family - dominant traits in every generation, recessive ones usually skip a generation
169
What do individuals with recessive traits in a pedigree usually result from?
Inner-family mating (usually first cousin)
170
How do different alleles of a gene arise?
Mutation to the gene nucleotide sequence creates a new allele which can be mutant (impairs function) or non-mutant (produces functional protein)
171
2 reasons inheritance patterns may be obscured?
1. Incomplete penetrance (have genotype but it is not expressed in phenotype)
2. Variable expressivity (phenotype expressed with different severity in different individuals)
172
What are X-linked genes?
Genes present anywhere on X chromosome
173
When is genetic linkage most evident?
Lack of independent assortment that means offspring do not follow expected phenotypic ratios
174
Difference between recombinant and non-recombinant progeny?
Recombinant = different allele combination from parent as a result of crossover
Non-recombinant = same allele combination as parent
175
If genes are far what will the crossing over of one gene produce?
2 recombinant, 2 non-recombinant
176
What is produced if genes are close and more than 1 gene in a row crosses over?
4 non-recombinant produced for those genes
177
What is the other way non-recombinant progeny are produced?
2 crossover events so the initial crossover is reversed
178
What does a low % of recombinants indicate?
Genes are far away from one another
179
What is the likelihood of a crossover event proportional to?
Length of interval between 2 points
180
What is a genetic map and what is it used for?
- Diagram showing position of genes on a chromosome
- Used to identify genetic risk of a disease, SNPs and mutations via markers to see if they cause a disease
181
How are mitochondria and chloroplasts inherited?
Uniparentally (usually maternally) and segregate independently from chromosomes in the nucleus SO if a mother has a trait in the mitochondrial genome is will always be passed on
182
How can maternal and paternal ancestry be traced?
Maternal = mitochondrial DNA
Paternal = X chromosome
183
4 sex determination mechanisms?
1. Chromosomal
2. Genic
3. Environmental
4. Sex chromosome aneuploidy
184
Difference between monoecious and dioecious?
Monoecious = individual has male and female reproductive structures
Dioecious = individual has either male OR female reproductive structures
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- 4 traits sex involves?
- 3 ways the traits can be categorised?
- 1. Genetics
2. Hormones
3. Morphology
4. Behaviour
- 1. Strict binary (male or female)
2. Bimodal (2 peaks in one trait)
3. Multivariate (many traits with many peaks)
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Difference heterogametic sex and homogametic sex?
Heterogametic sex = produces gametes with different types of sex chromosome
Homogametic sex = produces gametes that all contain the same type of sex chromosomes
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As the X chromosome is bigger than the Y chromosome they are not homologous, how is this overcome?
Have homologous tips so they can pair in cell division
188
What is haplo-diploidy?
Females are diploid, males are haploid (if egg is fertilised it is female, if it is not its male)
189
What is genic sex determination?
A sex-determining gene is present but no sex chromosome
190
What can environmental sex determination be affected by?
Temperature e.g. in turtles
191
What is:
- Sequential hermaphroditsm?
- Protogyny?
- Protandry?
- Sex change during life
- Female to male
- Male to female
192
How is determining the sex of flies different to humans?
Flies are determined by the ratio of X chromosome:autosome - e.g. normal chromosome separation and mating between a white-eyed female and a red-eyed male produces red-eyed female and white-eyed male BUT nondisjunction creates males with X chromosome and female with 2X and 1Y
193
What does the SRY gene on the Y chromosome determine?
Maleness and triggers male development
194
What do aneuploidies of sex chromosomes cause?
Disorders e.g. Turner syndrome
195
What do extra X chromosomes become?
Barr bodies which are just inactivated X chromosomes (but not all genes inactivated so are present in phenotype)
196
What is androgen-insensitivity syndrome?
- XY females make SRY and testosterone
- Mutations in androgen receptor mean no effects of testosterone
- No functioning reproductive system
197
What is parthenogenesis?
No male is needed for offspring fertilisation
198
Define:
- Sex limited?
- Sex biased?
- Sex linked?
- Genes present in both sexes but only expressed in one
- Genes present in both sexes but expressed more in one than the other
- Genes on sex chromosomes
199
Why are there more X linked traits than Y linked traits?
Y chromosome is shorter and it does not recombine
200
Which individuals will have a trait that is only found on the Y chromosome?
Males
201
3 male specific/beneficial traits?
1. Spermatogenesis
2. Testis-specific expression
3. Body colour
202
Which traits are shown in all male offspring?
Y-linked
203
What is X mosaicism?
Pattern of X chromosome inactivation in females
e.g. results in tortoiseshell cats or anhidrotic ectodermal dysplasia in humans
204
Why are there less women?
Female embryos less likely to survive
205
What will be produced if a female who is heterozygous for a mutant and non-mutant allele mates with an unaffected male?
1 male offspring that is affected
206
Who passes on X chromosome mutations?
Mother
207
What is criss-cross inheritance?
X chromosome in a male must be passed to a female in the next generation to the be displayed in the generation after that (females will not as mutation is recessive, nondisjunction stops the process) - these are called rare X-linked recessive alleles and only a female with an affected father can pass it on
208
How is paternal ancestry traced?
Origin of ancestors after migration found by looking at halotype (accumulation of Y chromosome mutations)
209
Define population?
Interbreeding groups of organisms in the same area
210
What causes genetic variation?
Mutation and recombination
211
What is an allele?
The fundamental unit of variation that specifies different DNA sequences at a locus (can vary by SNPs or structural differences?
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What do genes with different alleles result in?
Different phenotypes
213
What does the phenotypic variation contributed by a locus depend on?
Frequency of alleles
(Frequency of allele = number of allele /
total number of alleles)
214
What does evolution change?
Allele frequencies in a population (not individuals)
215
3 things population differences in allele frequencies show?
1. Migration/gene flow
2. Favouring of alleles
3. Phenotype variation associated with sequence differences
216
How to calculate genotype frequencies?
No. of individuals with genotype/no. of
individuals
217
What does Hardy-Weinberg state?
2 alleles in a diploid individual are randomly and independently sampled from a large gamete pool
218
Hardy-Weinberg equation?
p^2 + 2pq + q^2 = 1
- p = homozygous dominant
- pq = heterozygous
- q = homozygous recessive
219
- 5 assumptions of Hardy-Weingberg?
- What do they all act as?
- 1. Population is very large
2. Random mating
3. No migration in or out
4. No selection
5. No mutation
- A baseline to create a null model (ideal state) so certain assumptions can be seen and gene evolution can be measured
220
Large population:
- What does it eliminate?
- What does it minimise?
- What does it prevent?
- Sampling error
- Genetic drift as allele frequencies are stable
- Allele fixation
221
Random mating:
- What does this mean?
- What does it prevent?
- What does it minimise?
- What does it maintain?
- All individuals have an equal chance of mating regardless of genetic traits
- Assortative mating (decreases bias for alleles)
- Inbreeding (if it is not minimised homozygosity increases and deleterious alleles are exposed)
- Genetic equilibrium
222
No migration:
- What remains stable?
- What is prevented?
- Allele frequencies
- Gene flow
223
No selection:
- What does not change?
- What are alleles equal in?
- What are individuals equal in?
- Allele frequencies
- Fitness
- Chance of survival
224
No mutation:
- What does not change?
- What does it facilitate?
- Allele frequencies
- Theoretical predictions
225
3 predictions of Hardy-Weinberg?
1. Allele frequencies of a population do not change solely due to random mating
2. Genotypic frequencies are the product of allele frequencies and will be at these frequencies after a generation of random mating
3. Predicted genotype frequencies (equation)
226
What kinds of alleles are almost always in heterozygotes?
Rare and those that arise from mutation
227
What are the main issues with HW assumptions?
1. Non-random mating (changes allele frequencies)
2. Homozygous individuals inbreeding (which increases homozygosity and decreases heterozygosity) - can lead to inbreeding depression which causes reduced viability and fecundity (and then outbreeding occurs)
3. Self fertilisation (decreases heterozygotes and will eventually lead to only homozygotes)
228
What are the 2 ways alleles can be identical?
1. By state (just happens)
2. By descent (inbreeding)
229
When does mean fitness of a population reduce?
When F (inbreeding coefficient) increases
230
Deleterious recessives:
- Where are they protected from selection?
- When are they selected against?
- What happens if 2 copies are inherited?
- In a diploid population as they are spread across genome and protected by genetic load
- Generations of inbreeding that increases homozygosity exposes them
- Negative effects
231
What is genetic drift?
Random changes in allele frequencies by chance (some alleles lost and gained, alleles are fixed so some are lost, violates HW as population is finite)
232
What are genetic bottlenecks?
Drastic population reduction
233
What is a founder event?
New population founded by a few individuals
234
Natural selection:
- What happens as a result?
- What is overdominance?
- Allele fixation as the fittest allele is selected for
- Heterozygote has highest fitness so both alleles are maintained
235
- What is gene flow (migration)?
- What does it reduce?
- What does it cause?
- Alleles moved from one population to another over time (without it populations change and become different through isolation by distance)
- Genetic variation between populations
- Homogenisation of populations
236
What does recombination lead to?
New permutations as mutations are shuffled
237
What is allele fixation?
Process of one allele replacing all the other alleles in a population for that specific gene
238
3 ways of measuring genotype and allele frequencies?
1. Observable traits
2. Gel electrophoresis
3. DNA sequencing
239
Why can observable traits not be used solely?
Traits are usually encoded by a large number of genes and the phenotype is affected by genotype and environment
240
What can gel electrophoresis be used for?
Detecting mutations that affect amino acids as these alter the migration of the protein
241
What are polymorphisms?
Variable nucleotide positions
242
How are allele frequencies found from DNA sequences?
Counting mutation occurrences and multiplying by 2 and then dividing by number of individuals
243
Why can evolution occur without allele frequencies changing?
The frequencies of different genotypes may change
244
What does HW relate?
Allele and genotype frequencies
245
What is an allele's frequency the same as?
The probability of an allele being chosen in random mating
246
Examples of:
- Adaptive mechanism?
- Non-adaptive mechanisms?
- Natural selection
- Genetic drift, migration, mutation, non-random mating (cause evolution though)
247
Why do small allele changes have a small effect on a large population?
Small change to expected frequency
248
Non-random mating:
- What does it alter?
- What does it redistribute?
- Why does inbreeding depression occur?
- Genotype frequencies (NOT allele frequencies)
- Alleles already in gene pool
- Result of deleterious recessive mutation
249
What are:
- Discontinuous (qualitative) traits?
- Continuous (quantitative) traits?
- Qualitative traits?
- Quantitative traits?
- Traits with few classes of categorisation
- Traits with a long scale of measurement
- Complex traits with genetic and environmental influence
- Traits that can be complex if categories reflect continuously variable underlying traits
250
What is meant by biomdal?
2 peaks of frequency of considerable size of a continuous trait
251
What are meristic traits?
Countable traits that are determined by multiple genetic and environmental factors
252
What are threshold traits?
Measured by presence or abscence (e.g. susceptibility to disease)
253
Why are complex traits usually polygenic?
A single genotype cannot make up a distinct phenotype so many genotypes are required
254
What is continuous variation?
Multiple genes underlying a trait
255
What is phenotypic variance?
The total amount of variation among individuals in some traits
256
Equation for phenotypic variation (Vp)?
Vp = Vg + Ve + Vge
Vg - genetic variation
Ve - environmental variation
Vge - genotype-environment interaction variance
257
Difference between heritable and non-heritable variation?
Heritable - reason for parent-offspring resemblance (additive genetic variance (Va))
Non-heritable - genetic variation that does not contribute to parent-offspring resemblance (dominance genetic variance (Vd) and epistatic variance (Vi))
258
Equation for genetic variation?
Vg = Va + Vd + Vi
259
- What is broad-sense heritability?
- Equation?
- Proportion of phenotypic variation attributable to all types of genetic differences between individuals
- H^2 = genetic variance / phenotypic
variance
260
What is narrow-sense heritability?
Proportion of phenotypic variation that contributes to the resemblance between parents and offspring (proportion of trait variation that is 'additive genetic')
261
What is regression?
Predicting the value of one variable if the value of the other is given
262
What is the regression coefficient?
An indicator of how much one value changes on average per increase in the value of another variable (represents the slope of the regression line)
263
What aspects of the social environment can alter phenotype via indirect genetic effects?
Aggression, parental care, intrafamilial interactions, competition and cooperation
264
What are maternal effects?
Causal influence of maternal genotype/phenotype on offspring
265
- As organisms are not univariate, what can be said about the traits?
- If correlation is 0?
- If correlation is >0?
- They can be correlated using a genetic correlation plot which correlates via shared genetic basis
- Even distribution
- Can predict trait 2 based on trait 1 (uneven distribution of trait combinations)
266
What is pleiotropy?
Multiple effects from one locus (single gene would undergo pleiotropy to trigger many traits)
267
What is not made when there is no recombination?
No new halotypes
268
Linkage disequilibrium:
- What is it?
- What does it act as?
- How is it used for genetic correlation?
- What undoes linkage disequilibrium?
- When else are traits genetically correlated?
- Random assortment of alleles at loci is disrupted (with a statistical association)
- Origin of correlation
- Favoured pairings of chromosomes are more likely to be inherited (equal frequencies of coupling affected - dominant and recessive alleles on the same chromosome vs 1 dom and 1 rec)
- Recombination
- When there are only coupled gametes
269
What is repulsion and coupling?
- Repulsion is when dominant traits repel and recessive traits repel (1 dominant and 1 recessive together)
- Coupling is when traits that are both recessive or both dominant associate together (e.g. 2 dominant alleles)
270
What are trade-offs?
An origin of correlation whereby traits trade-off due to limited resources (such as seed size and number)
271
Correlational selection:
- What is it?
- When does genetic correlation arise?
- The fitness of combinations of phenotypes is measured over time for survival (using recapture)
- When fitness increases due to right behaviour arising for patterning
272
What constrains some correlated traits such as birds' vision?
Physics
273
Why can correlations be misleading?
Trade-offs occur on a smaller scale of a bigger picture (e.g. different environments will show variation within themselves, but in the bigger picture it will look like all the environments are correlated)
274
When can the effect of a locus be measured independently of other loci?
When there are no interactions or epistasis
275
When does epistasis occur?
When effect of alleles at a locus depends on alleles present at other loci (loci interact in a statistical sense, the appearance of this interaction depends on the presence of variation at each locus)
276
What is the broad term for epistasis?
Genetic background dependence
277
What does epistasis come from?
The fact genes have no effect on their own and they just contribute to regulatory networks and biochemical pathways etc...
278
Interaction networks:
- What is the pairing of epistatic interactions said to be?
- What do the interactions occur through?
- Naive
- Complex connected networks
279
How are loci located to see quantitative effects?
- Quantitative Trait Locus (QTL)
- Genome-Wide Analysis (GWA)
280
Quantitative trait locus (QTL):
- What is identified?
- What does it not have to be caused by?
- Mainly associated with?
- What does it use?
- What does it identify that is linked to the markers?
- How are they usually identified?
- Location in the genome that causes different values of the trait in question
- Changes in exons (can be in introns)
- Differences in gene expression
- Genetic markers
- Causal variation
- By crossing strains that are fixed for dominant and recessive alleles - loci underlying phenotypic differences looked for
281
Genome-wide analysis:
- What is shown?
- What is plotted?
- What is identified?
- Way of plotting?
- Marker positions across a chromosome
- QTLs and their significance
- Loci associated with trait variation
- A Manhattan plot that shows significance of SNPs
282
Genetic markers:
- What do they allow?
- What do they show different types of?
- What do they differ in?
- Differentiation between different alleles
- Differences
- The technology used to assay them and the evolutionary processes shaping variation (e.g. mutation)
283
3 main roles of markers?
1. Providing information on genetic differences
2. Finding complex trait genetics like QTLs
3. Measuring genetic diversity
284
What is assay?
Determination of composition by methods like SNPs, DNA sequencing and CAPs etc...
285
Copy number variation (CNVs):
- What are they?
- Are they reflected in markers?
- 3 ways of detecting them as its so hard to detect them?
- Identical duplicated areas that can create phenotypic variation
- No
- 1. Level of sequence coverage measured
2. Regions showing deviation incoverage measured
3. Assay individuals for polymorphic pattern
286
What was used to detect protein variation before DNA technology?
Allozymes - different electric charges meant different migration through electric field affected
287
Where are markers derived from?
Raw DNA (oldest DNA methods profiled DNA directly) and rely on amplication by PCR
288
What is restriction fragment length polymorphism (RFLP)?
Undegraded DNA is cut into fragments at specific sites using restriction sites - different lengths of varies due to differences in number of large DNA repeats
289
Simple sequence repeats:
- What is used and why?
- How are repeats identified?
- What can they distinguish?
- Amplified using?
- Short tandem repeats (micro-satellite markers) because they are highly polymorphic due to rapid mutation
- More repeats = lower distance moved on gel
- Many alleles at a locus
- PCR
290
SNP markers:
- What are they?
- Why are they useful?
- Why can they track halotypes?
- A single-base difference between alleles
- Abundant
- Each block that is inherited as a unit for measurement is a halotype and mutations create new halotypes
291
What is low coverage sequencing?
A low number of reads per base of genomic DNA (coverage) which is used to infer halotypes (lots of data about the genotype is missing but it is inferred)
292
Mitochondrial genome markers:
- When are they used?
- 3 reasons why they are good?
- Population studies
- 1. No recombination (uniparental inheritance)
2. Haploid
3. Highly variable sequence
293
Genotyping arrays:
- What are identified?
- How is the genotype identified?
- SNP loci
- K-mer probes bind to DNA and hybridise it to spots on array
294
3 pros of genotyping arrays?
1. Low error
2. Low cost (if using past arrays)
3. Reliable and comparable
295
4 cons of genotyping arrays?
1. Needs adequate information on SNP loci
2. Costly to create new array
3. Fixed SNP set may not represent all variation
4. Biased to reference group to identify SNPs
296
What is an illumina infinium assay?
Silica beads in wells of an array have a probe with a complimentary SO-mer sequence that stops one base pair from SNP location and then a single base extension adds a label to the SNP position
297
What is chromosome painting?
Different genealogies are assigned genomic locations and segments are assigned different origins of ancestry
298
4 things ancient DNA tells us?
1. How diseases evolved
2. Migration of populations
3. Interbreeding
4. Evolution
299
What is environmental DNA and what does it tell us?
- It is DNA shed by organisms into the environment (e.g. air, water soil and sediment)
- It is a non-invasive way of detecting species diversity, finding DNA markers and can add a unique challenge to research via a new discovery
300
How is environmental DNA (eDNA) retrieved?
- Filtering water to catch DNA
- Sediment coring to retrieve DNA from different layers of the sediment and showing the previous composition of the ecosystem
301
4 applications of eDNA?
1. Quickly and comprehensively assess which species were/are present in an ecosytem
2. Easy detection of rare or invasive species
3. Monitoring ecosystem health e.g. keystone species
4. Forensic ecology (identifying illegal trade)
302
What is meta-barcoding?
Type of bioinformatic technique to identify diversity of species in the same ecosystem
303
5 pros of eDNA?
1. Non-invasive (no harm to organisms)
2. Very sensitive even at low abundances
3. Can access hard-to-reach places
4. Comprehensive (entire ecosystem)
5. Standard and repeatable
304
4 cons of eDNA?
1. DNA degradation affects accuracy
2. Contamination with foreign DNA
3. Taxonomic resolution of matches can be low
4. Standardisable workflows are specific to different environments (difficult to choose which one)
305
