Genetics Flashcards
1
Q
Wild type
A
An unmodified natural isolate of a species
2
Q
Mutant
A
An organism that differs from the wild type as a result of a specific change to its DNA sequence
3
Q
Mutation
A
A specific change in the DNA/RNA sequence of an organism that is different from that in the wild type
4
Q
Allele
A
Different forms of a gene that arise by mutation and that are found at the same place on a chromosome in both the wild type and in a mutant
5
Q
Phenotype
A
An identifiable or observable trait that can be altered by a mutation
6
Q
Genotype
A
The nucleotide sequence of a region of DNA
7
Q
Advantages of using bacteria?
A
– Relatively simple organisms
– Easy to genetically manipulate
– Short generation times
– Haploid organisms
8
Q
Why is bacteria being a haploid organism an advantage?
A
It is much easier to identify cells with a particular type of mutation as they have an immediate effect on the behaviour/appearance of the organism
9
Q
What are Darwinian principles?
A
Mutations occur randomly and are passed on by vertical gene transfer
10
Q
How do bacteria inherit DNA?
A
Via vertical gene transfer and lateral gene transfer
11
Q
What is vertical gene transfer?
A
Inherit DNA from parents
12
Q
What is lateral gene transfer?
A
Inherit DNA from other bacteria / viruses in the environment
13
Q
What is genetic transformation?
A
The ability of a bacterial cell to take up cell-free DNA from the environment. First discovered in 1928 by Fred Griffith
14
Q
What is bacterial conjugation?
A
Gene transfer from one bacterial cell (the donor) to another (the recipient) by direct cell-to-cell contact
15
Q
What is transduction?
A
Gene transfer mediated by a bacterial virus
16
Q
What is the central dogma?
A
DNA makes RNA makes protein
17
Q
What are the 3 stages of transcription?
A
Initiation, elongation, termination
18
Q
What is initiation?
A
RNA polymerase binds to a promoter sequence in the DNA and starts transcription
19
Q
What is elongation?
A
RNA polymerase moves along the strand of DNA using the template strand to decode the DNA to RNA
20
Q
What is termination?
A
RNA polymerase recognises sequence in the DNA that tells it to stop synthesising RNA
21
Q
What are the most common types of RNA?
A
Messenger RNA, ribosomal RNA, transfer RNA
22
Q
What term is used to describe the direction of chromosomal replication?
A
Bidirectional
23
Q
Name 6 types of mutation
A
Base pair changes, frameshifts, deletions, inversions, duplications, insertions
24
Q
What are the 3 potential consequences of base change mutations?
A
Silent mutation, missense mutation, nonsense mutation
25
What is mutation frequency?
Frequency at which mutation occurs over time
26
Equation for mutation frequency
MF =m / N
Where m= number of mutants and N= total number of bacteria
27
How do frameshift mutations occur?
By the insertion or deletion of a number of bases not divisible by 3
28
What are the 2 types of base changes that can occur?
Transitions and transversions
29
What is a transition (base change)?
Purine → purine or pyrimidine → pyrimidine
30
What is transversion (base change)?
Purine → pyrimidine or pyrimidine → purine
31
How many codons are stop codons?
3
32
Name 3 ways in which we can select mutants
Negative selection, enrichment, positive selection
33
What is negative selection?
Selects against the mutant growing
34
What is enrichment?
The use of negative selection to inhibit growth of mutants and then killing wild type growing cells using an antibiotic
35
What is positive selection?
Uses selective conditions where only the mutants win grow
36
Genome
The sum total of genetic material in an individual organism
37
Genomics
The acquisition, storage, retrieval and analysis of DNA sequence data
38
Which direction does E. coli replicate in?
Bidirectionally
39
How many proteins does E. coli encode?
4400
40
What rate does E. coli replicate at?
850 bases per sec per replication fork
41
What is metagenomics?
The study of genetic material recovered directly from environmental samples
42
What is recombinant DNA?
When 2 pieces of DNA are ligated under artificial conditions to perform a modified function
43
Function of DNA ligase?
Sticks fragments of DNA together
44
Function of Taq polymerase?
PCR - creates multiple copies of DNA fragment
45
Function of reverse transcriptase?
Copies RNA into DNA
46
Name 2 types of cleavage patterns
Symmetrical cleavage (blunt ends)
Asymmetrical cleavage (sticky ends)
47
Intron
Any nucleotide sequence within a gene that is removed by RNA splicing during maturation of the final RNA product
48
Exon
Any part of a gene that will encode a part of the final mature RNA produced by that gene a introns have been removed by RNA splicing
49
Advantages of bacteria as a host
Simple cells
Short generation time
Large yields of product
Low costs
50
Disadvantages of bacteria as a host
Eukaryotic proteins can fold correctly and lose biological activity
Proteins can be toxic to the bacterial cell
No post- translational modifications
51
Advantages of yeast as a host
Simple unicellular eukaryote
Resembles mammalian cells
Grows quickly and cheaply
Performs post-translational modifications
52
Disadvantages of yeast as a host
Contains proteases → degrade some recombinant proteins
Post - translational modifications may differ from mammalian cells
53
Advantages of insect cells as a host
High-level protein expression
Correct folding of mammalian proteins
Post-translational modifications
Cheaper than mammalian cell culture
54
Disadvantage of insect cell as a host
Post- translational modifications may differ from mammalian cells
55
Advantages of mammalian cells as a host
Best place to produce mammalian proteins
Correct folding of mammalian proteins
Post-translational modifications
56
Disadvantages of mammalian cells as a host
Complex cells
Grow to lower cell densities
Expensive
57
What is a model organism?
A well established experimental biological system
58
Characteristics of model organisms
Rapid rate of development
Easily manipulated
Short lifespan
Readily available
Large numbers of offspring per generation
59
3 types of model organism
Genetic, genomic, experimental
60
Name some common eukaryotic models for genetic analysis
Yeast, fruit fly, worm, zebrafish, mouse
61
Homologue
A gene related to another gene by descent from a common ancestral DNA sequence
62
Orthologue
Genes in different species that evolved from a common ancestral gene
63
Prologue
Prologues are genes generated by a duplication event (e.g. Human alpha and beta haemoglobin genes)
64
Define gene knockout
Gene sequences are completely or partially removed and gene expression is completely eliminated
65
Define gene knockdown
Techniques that reduce/interfere with the expression of the gene
66
Characteristics of S. Cerevisiae
Small size and simple growth and storage conditions
Rapid growth rate
Can exist as diploid or haploid cells
12.8 Mbp genome~ 6000 genes
67
What is a disease model?
A mutant mode organism that mimics the phenotypes observed in a human disease
68
Characteristics of S. pombe
Fission yeast - splits to divide
13 Mbp with ~5000 genes
69
Characteristics of Drosophila melanogaster
Small ~ 3mm
Life cycle approx 2 weeks, females can lay up to 100 eggs per day
Genome 165 Mbp, encoding ~14,000 genes
70
Characteristics of C. elegans
Small (~1mm)
Short life cycle, egg to egg takes approx 3 days
Short lifespan 2-3 weeks
Genome 97 Mbp, 5 pairs of autosomal chromosomes and one pair of sex chromosomes
~ 20,000 genes
71
Characteristics of zebrafish
Lay ~ 200 eggs per week = ~35,000 eggs ( 2-4 years)
Sexually mature by 3-4 months old, a generation interval of 2-3 months
Transparent embryos
1.7 Gbp genome - 25 chromosomes
72
Characteristics of mouse
25,000 genes on 20 chromosomes (2.6 Gbp)
2 month breeding cycle, 6-15 offspring perlitter
73
Name some diseases a mouse can model
Down syndrome, cystic fibrosis, cancer, glaucoma, epilepsy, heart disease, muscular dystrophy, ovarian tumours
74
Pros and cons of mouse disease models
Pro- A very powerful approach to understanding the role of a particular gene in a mammal and its role in a disease
Con- The production of knockouts is very expensive and time consuming. Also ethical considerations
75
Banding pattern for G - banding
Dark bands are AT rich
76
Banding pattern for R- banding
Dark bands are GC rich
77
Banding pattern for Q - banding
Dark bands are AT rich
78
Banding pattern for C - banding
Dark bands are constitutive heterochromatin
79
What is letter for short arms?
P
80
What is the letter for long arms?
Q
81
What are telomeres?
Specialised regions at the end of chromosomes
82
What are the major functions of telomeres?
1. They allow the cell t distinguish a real chromosome end from an unnatural end caused by a chromosome break
2. They solve the problems that cells have replicating the ends of linear chromosome – the end replication problem
83
What is euchromatin?
Relatively uncondensed chromatin associated with active (expressed) genes
84
What is heterochromatin?
Condensed chromatin, associated with repetitive gene poor regions that are inactive (silenced)
85
What are minichromosomes?
Relatively short chromosomes but rich in genes
86
What are B chromosomes?
Additional chromosomes possessed by some but not all individuals in a population
87
What are holocentric chromosomes?
Do not have a single centromere but have multiple kinetochores throughout their length
88
What are polytene chromosomes?
Giant chromosomes
89
What are kinetochores?
Protein structures located at the centromere that serve as an attachment point for the mitotic spindles
90
What is the centrism?
A region of the cytoplasm containing a pair of centrioles
91
What is the synaptonemal complex?
A nucleoprotein zipper that forms between the paired homologous chromosomes
92
What is a trisomy
3 copies of a particular chromosome rather than 2
93
What is aneuploidy?
Chromosome number is not an exact multiple of the haploid number
94
Trisomy 8
Warkany syndrome 2
95
Trisomy 12
Chronic lymphocytic leukaemia
96
Trisomy 13
Patau syndrome
97
Trisomy 18
Edward's syndrome
98
Trisomy 21
Down syndrome
99
What is the klinefelter karyotype?
More than one X chromosome
100
What is the turner karyotype?
Single X chromosome
101
Features of the Y chromosome
PARs = pseudo autosomal regions – share pomology with X chromosome
MSY = male specific region of the Y – does not synapse with the X chromosome
SRY = sex determining region Y – produces testis determining factor (TDF) which triggers undifferentiated gonadal tissue of the embryo to form testes
102
What is the Lyon hypothesis?
1. Inactivation is random at an early point in development
2. Once inactivated all progeny cells have the same X chromosome inactivated
103
Which codon does translation start on?
Methionine
104
What are Mendel's laws?
1st law - the 2 copies of each gene segregate
2nd law - the copies of each gene segregate independently of those of other genes
105
Name some autosomal recessive conditions
Albinism, tay-sachs, cystic fibrosis
106
Name some autosomal dominant conditions
Huntington's disease, polydactyly, achondroplastic dwarfism
107
Name some x-linked recessive disorders
Haemophilia, deuteranopia (red-green colour blindness)
108
Name an X - linked dominant disorder
Vitamin D - resistant rickets
109
What is epistasis?
A situation where one mutation hides the phenotype of another
110
How is recombination frequency expressed?
As a percentage
111
What is the equation for recombination frequency?
(No. Of recombinants/ total progeny) x 100
112
What are syntenic genes?
Those grouped in the same way on the chromosomes of two or more species
113
What is modern genome organisation?
The result of mistakes in the replication and segregation of ancestral genomes
114
Result of duplication events
Generation of multi-gene families, within which individual genes evolve to have different functions
115
What is a haplotype?
A set or linked polymorphic markers
116
How old are prokaryotes?
Very old - predate 3.75BYA
117
Are eukaryotes older or prokaryotes?
Prokaryotes
118
How did the mitochondrion originate?
As an endosymbioticbacterium that colonised the common ancestor of eukaryotic cells approximately 2BYA
119
How do we know mitochondria were bacteria?
They have their own small genome and its genes are bacterial genes
120
What is Hsp 70
70 kD mitochondrial heat shock protein
121
What are the roles of Hsp 70?
1. Allows proteins made in the cytosol to be imported into the mitochondrion
2. The assembly of Fe-S clusters (essential cofactors of some mitochondrial proteins that function in the ETC)
122
What are the two main theories for the origin of modern humans?
The multinational model and the Out of Africa hypothesis
123
Why is yeast a good model for human genetic disease?
These diseases are commonly associated with conserved fundamental processes such as the cell division cycle
124
Examples of cancer linked genes found in Saccharomyces cerevisiae
DNA repair gene - MSH2
Coul cycle checkpoint gene - ATM
125
Examples of human disease genes found in Saccharomyces cerevisiae
WRN/BLM genes
NF1
126
What is developmental biology?
The study of the process by which organisms grow and develop
127
What is developmental genetics?
- Uses developmental biology knowledge and techniques to understand congenital anomalies and genetic disease
- Involves the use of model organism to study developmental processes
128
How long is human pregnancy usually?
38-40 weeks
129
How is human pregnancy broken up?
Into embryonic (up to 8 weeks) and foetal ( 8 weeks - term) periods
130
When does organogenesis occur?
During embryogenesis
131
When do most congenital anomalies occur
In first 8 weeks
132
What is a model organism?
A well established experimental biological system
133
What was the last common ancestor of humans and flies?
Ikaria wariootia - 550 million years old
134
Why is Drosophila useful?
- Genome sequence
- Short life cycle
- Easily accessible larvae
- Most genes have homologues in mammals
135
Why are zebrafish useful?
- Transparent as embryos
- Genome sequenced
- Easy to manipulate genetically and experimentally
- Capable of regenerating many body parts
136
Why are amphibians useful?
- Large embryos that can be easily manipulated
- Capable of regenerating many body parts
137
Why are birds useful?
- Large accessible eggs
- Easy to manipulate and image
- Genetics very complex
138
Why are mice useful?
- Genome sequenced
- Large numbers of mutants available
- Relatively rapid life cycle
- Possible to manipulate genome
139
Why do we need animal models?
- Can't experiment on humans
- Can’t model disease processes in cell culture
- Can’t test toxicity of new drugs or disease treatments in cell culture
140
What are 3 fundamental processes of developmental biology?
1. Morphogenesis
2. Differentiation
3. Growth
141
What is morphogenesis?
The emergence of form
142
What is differentiation?
Process by which cells become specialised
143
What is body plan?
The map of an organism
144
Where does the antero-posterior axis run?
Head to tail
145
Where does the dorso-ventral axis run?
Back to belly
146
Where does the left-right axis run?
Between the two lateral sides of the embryo
147
What are the four components to cell-signalling?
- Release and transmission of signal by source cell
- Reception of the signal by the target cell
- Transduction of the signal
- Cellular response
148
What are morphogens?
Growth factors that pattern the embryo
149
What are congenital malformations?
Those already present at birth
150
What are possible genetic causes of congenital malformations?
Chromosomal defects, syndromes, single genes, multi-gene interactions
151
What are possible environmental causes of congenital malformations?
Maternal diabetes, fever, prescription drugs, recreational drugs, pollutants, dietary deficiencies
152
What is cytogenetics?
A branch of genetics concerned with how the chromosomes relate to cell behaviour
153
When do we see chromosomes?
In mitosis
154
What is metacentric?
P arm and q arm approx. same length
155
What is sub-metacentric?
P arm shorter than q arm
156
What is acrocentric?
Satellite structure present on p arm
157
What does a BLAST search allow you to do?
Identity similar protein sequences to one that you search with?
