Module 2: Molecular Biology & Genetics And Module 3: Human Molecular Genetics Flashcards
(175 cards)
1
Q
Aneuploidy
A
An abnormal number of a particular chromosome
2
Q
Example of aneuploidy, and what causes it
A
Down syndrome caused by trisomy 21.
Three copies of chromosome 21, caused by failure of chromosomes to separate during meiosis.
3
Q
Nondisjunction
A
Failure of chromosomes/ chromatids to separate during anaphase of cell division
4
Q
What does XXY cause?
A
Klinefelter syndrome
5
Q
What does XO cause?
A
Turner syndrome
6
Q
Polyploidy
A
Possession of multiple sets of chromosomes
7
Q
How does polyploidy come about?
A
Gametes contain same number of chromosomes as parent cell (2n). When fertilised, the two gametes produce a tetraploid (2n + 2n = 4n)
8
Q
Example of a triploid species
A
Bananas
9
Q
What is a sure cause of infertility? Why?
A
Odd number of chromosome sets. Not all chromosomes will have homologous chromosomes to pair with due to gametes having different chromosome set numbers
10
Q
What are the four chromosomal aberrations?
A
Deletion
Duplication
Inversion
Translocation
11
Q
Deletion, and what disease can it cause?
A
Small part of a chromosome is removed
Lejeune syndrome/ cri du chat: deletion of the top of short arm on chromosome five
12
Q
Duplication
A
One part of a chromosome is repeated
13
Q
Inversion, and what effect does it have?
A
Part of a chromosome is taken out, then re-added in the reverse order.
Inversion prevents the production of viable zygotes during meiosis, because crossing over results in uneven chromosomes.
14
Q
Translocation
A
Part of a chromosome is moved to a non homologous chromosome
Can be reciprocal
15
Q
Philadelphia translocation
A
Ends of chromosomes 9 and 22 are swapped (translocated)
95% of the time this results in myeloid leukaemia
16
Q
Familial Down syndrome
A
One 14 chromosome and one 21 chromosome are joined in the parent.
A potential gamete, when fertilised, will produce an embryo with three chromosome 21’s.
17
Q
Why do we inactivate an X chromosome?
A
Because only one X is necessary- females have an extra one.
18
Q
What does the inactivated X chromosome show up as?
A
Barr body
19
Q
When is the X chromosome inactivated?
A
After four days- after the cell has divided several times
20
Q
How is the X chromosome inactivated, and which one is chosen?
A
DNA is packed closer together, and methyl groups are added to prevent enzymes from interacting with it.
Can be from mother or father
21
Q
Describe the three components of the Central Dogma of Molecular Biology and their roles
A
DNA- information
RNA- messenger
Protein- worker
22
Q
Which five processes occur in the central dogma of molecular biology?
A
Transcription Translation Reverse transcription DNA replication RNA replication
23
Q
Gene expression
A
Process by which information from a gene is used in the synthesis of a functional gene product
24
Q
Functional gene product (2)
A
Protein or non-coding RNA
Product of gene expression
25
What does a gene do?
Produces a type of RNA with a specific function
26
Transcription
Synthesis of double-stranded DNA from a single-stranded RNA
27
Which enzyme catalyses transcription?
RNA polymerase
28
Coding strand
The DNA strand containing the information the cell needs
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Non-coding strand
The strand that doesn’t contain information the cell needs. Is there for replication
30
Other name for non-coding strand
Template strand
31
In which direction along the template strand does RNA synthesis occur?
3’-5’
32
Three stages of transcription
Initiation
Elongation
Termination
33
Which stage of transcription differs between eukaryotes and prokaryotes?
Termination
34
Where does initiation of transcription start?
At the TATA box in the promoter region of the template strand
35
TATA box
A segment of DNA that contains bases T,A,T,A / is AT heavy
36
How does initiation of transcription start?
TATA box allows transcription factors to bind
37
Transcription factors
Proteins that bind to DNA and help bind the RNA polymerase
38
What is the name of the complex which includes transcriptions factors and RNA polymerase?
Transcriptional initiation complex
39
RNA polymerase function
Starts mRNA synthesis, contains hydroxyl group which means it doesn’t need a primer
40
Elongation (transcription)
RNA polymerase continues to synthesise mRNA from template strand in the 5’-3’ direction
41
Which regions flank the coding sequence in a gene?
5’UTR and 3’UTR
42
UTR
Untranslated region
| - a region which is copied in transcription but is not translated
43
Which nucleotide connects to the 5’UTR before translation?
5’G cap
| A chemically modified guanine nucleotide
44
5’G cap function
Prevents enzymes from degrading mRNA
45
What connects to the end of the 3’UTR?
Poly-A tail
46
Functions of poly-A tail (2)
Prevents enzymes from degrading RNA
Facilitates transport of mRNA from nucleus into cytoplasm, through a nuclear pore
47
What connects to the 5’UTR before transcription?
Promoter region, including TATA box
48
What changes does the gene undergo after transcription?
Promoter region is lost
5’G cap and poly-A tail are added
49
Which part of the gene makes it through translation?
Coding sequence
50
Introns
Non-coding regions
51
Exons
Coding regions
52
Splicing
Process of removing introns and joining exons together in the coding sequence before translation
53
Before splicing, what kind of RNA exists?
Pre-mRNA (precursor)
54
After splicing, what kind of RNA exists?
mRNA (mature)
55
What is the name of the triplet-based genetic code?
Triplet codon hypothesis
56
How many possible codons are there? How many codons code for amino acids?
64
61
57
UAA UAG UGA are what kind of codons?
Stop codons
58
Start codon
AUG
59
Adaptor molecule between mRNA and amino acid
tRNA
60
Structure of tRNA
Single strand of RNA, 70-80 nucleotides in length
Looped and twisted into 3D L-shape
61
Where does the tRNA connect the amino acid?
At the amino acid attachment site
62
Anticodon-triplet
The triplet of bases on a tRNA which base pairs to the mRNA strand
63
What happens at the amino a acid binding site?
An enzyme joins tRNA to an amino acid by using ATP to form a covalent bond
Different enzyme for each amino acid
In general, it’s called aminoacyl-tRNA synthetase
64
Three stages of translation
Initiation
Elongation
Termination
65
Ribosome structure
Small subunit
Large subunit with A P and E sites
- above the P site is the exit tunnel
66
Locations of ribosomes (2) and where the proteins go
Bound to the rER- used within the plasma membrane or exit (exocytosis)
Free in the cytosol - released into the cytosol and used in the cell
67
Describe initiation (translation)
Small subunit meets tRNA molecule carrying methionine
They find and bind to the 5’G cap of the mRNA
They scan along the mRNA until the start AUG codon, where large subunit joins and methionine is carried by P site
68
Describe elongation (translation)
A charged tRNA arrives at the A site of the large subunit
Simultaneously:
- amino acid at P site attaches to new amino acid at A site- forming peptide bond
- ribosome moves along mRNA, shifting positions of the tRNAs so the growing polypeptide sits in the exit tunnel
Then the uncharged tRNA exits out the E site by detaching from its codon
69
Charged tRNA
tRNA molecule with an amino acid attached
70
Describe termination (translation)
Release factor enters A site once ribosome reaches a stop codon
- breaks bond between P site and final amino acid using water
Polypeptide chain detaches from the tRNA, and both subunits and mRNA dissociate
71
Genotype
Set of genes/ DNA combinations responsible for a particular trait
72
Phenotype
Physical expression of a genotype
Defined by what happens at the protein level
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_____ variation commonly leads to _____ variation
Genetic
| Phenotypic
74
F1
First filial generation
75
F2
Second filial generation
76
Monohybrid
A cross that is heterozygous with respect to one specific gene
77
What does Mendel’s peas experiment show about how information is inherited?
Information is passed on to offspring packaged in particles called genes
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Test cross
Crossing a dominant phenotype with a homozygous recessive genotype to find the genotype of the first one
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Mendels law of segregation
Genes segregate at meiosis so that each gamete contains only one of the two possessed by the parent
(Diploid—> haploid)
80
Mendels law of independent assortment
Alleles of different genes assort independently during gamete formation
(Where R or r goes does not determine where Y or y goes)
81
Product rule is for ?
Independent events
82
Sun rule is for ?
Mutually exclusive events
83
Polymorphism
When one gene controls more than one allele
84
Incomplete dominance
One allele is partially dominant, so a new phenotype is produced
This is not blending
85
Co-dominance
Both phenotypes exist side by side
86
Example of co-dominance
AB blood type
87
Polygenic traits
Traits that are controlled by groups of genes
88
If you graphed a polygenic trait of the population, what would it look like?
Normally distributed
89
How does the environments effect on a phenotype change the variation?
It smooths out differences
90
What is the name of a trait which is determined by genes on the X or Y chromosome? Give an example
Sex-linked trait
| Red-green colour blindness
91
Hemizygous
Describes an individual who only has one allele. Often a male, referring to a gene on the X chromosome.
92
Will the sons of a father with red green colour blindness also have this?
No- it is a trait on the X chromosome- which fathers do not give to sons
93
Recombinant type
A new genotype which wasn’t one of the parents
94
Parental type
A genotype of one of the parents
95
How do recombinant types occur?
They are a result of crossing over during meiosis, where homologous chromosomes exchange parts of a gene and form chiasmata
96
The smaller the distance between two genes, the _____ the recombination frequency?
Smaller
97
Recombination frequency
Percentage of gametes expected to be recombinant types
98
centiMorgan cM
A unit of recombination (1% = 1cM) used for a genetic map
99
Hardy-Weinberg equation (proportions of alleles)
p^2 + 2pq + q^2 = 1
100
If 1 in 2500 people have a rare disease, how is this expressed in p and q terms?
q^2 = 1/2500
101
Causes of genetic change in a population (7)
```
Non-random mating
Random genetic drift
- bottleneck effect
- founder effect
Natural selection
Gene flow or migration
Mutation
```
102
Two types of non-random mating
```
Inbreeding
Assortative mating (mating within same phenotype)
```
103
Random genetic drift
A random change in allele frequencies due to sampling error over generations
104
Sampling error
Who happens to leave offspring out of a population
105
Which factor will increase random genetic drift?
Size of the population (smaller)
106
Bottleneck effect
An event causes most of the population to die, and the remaining alleles don’t show as much genetic diversity
107
Founder effect
genetic diversity of new population in a new location is limited by the genotypes of the founding organisms
108
Stabilising selection
Mean stays the same, variation is reduced
Type of natural selection
109
Directional selection
Type of natural selection
Mean changes toward one extreme
110
Disruptive selection
Type of natural selection
Favours the two extremes of the population
111
Sexual selection
A type of natural selection
Favours the phenotype that attracts females more (or males)
112
Frequency dependent selection
Type of natural selection
Favours the rarer phenotype
113
Cline
Geographic change in genetic/ phenotypic composition
| As location changes, frequency of a genotype changes
114
Comparative genomics
Comparing genomes to find what is conserved and what is different between or within species
115
Aligning (sequences)
The process of lining sequences up next to each other and marking each point where sequences are the same
116
What might differences in genomes within a species be associated with? (3)
- disease
- characteristics
- evolutionary history
117
Which two species are the closest relatives of humans?
Chimpanzee and bonobo
118
We share all our genes with chimps. How do we differ genetically?
We use the genes in different ways
119
What happens when DNA degrades?
It's sequence changes
120
What can ancient DNA be used for?
To determine the relationships of extinct animals
121
Closest relative of modern humans
Neanderthal
122
Why are Neanderthal remains good for DNA extraction?
They are in cold, sealed caves
123
What types of Neanderthal evidence have been found?
Tools, art, jewellery
124
Some people carry Neanderthal DNA. What does this mean?
They carry alleles that arose in Neanderthals rather than in modern humans
125
Why do some people carry Neanderthal DNA
When homosapiens left Africa, some interbred with Neanderthals
126
What allele does Denisovan contribute to the Tibetan population?
One that allows them to handle hypoxia (low oxygen)
127
How can we work out what the function of a gene is?
By studying organisms that are mutant for that gene
128
Polydactyly
Above average number of fingers or toes
129
What is the role of the gene which causes polydactyly?
To prevent polydactyly
The mutant form of this gene is unable to do this, so extra fingers or toes grow
130
Does variation in a gene always affect phenotype?
Only sometimes
131
How is mutation linked to variation?
Mutation is a subset of variation
132
Do mutations affect fitness?
Not all the time
133
Myotonia congenita
Inherited condition in which muscles fail to relax after contraction,
Due to defect in the gene which encodes a chloride channel receptor
134
Three functional molecular genetics techniques
Genetic screen
Transgenesis
Targeted mutation
135
Genetic screen
Mutations are introduced to a gamete by treating them with mutagens
The organism is studied for any changes in phenotype
136
Mutagen example
X rays or chemicals
137
What makes a model organism
It can be easily raised in a controlled environment (not too large or too long lifespan)
Easy to manipulate genetically
138
Transgenesis
Foreign DNA is added from one organism into another (inserted into embryo pronucleus)
DNA code is universal- DNA from one organism can be used in another
139
Transgenesis
The gene placed into another organism during transgenesis
140
Novel variant
A variation of a gene in an organism which isn’t present in the parents’ genomes
141
Targeted mutation
Damage or modify the gene we are interested in to work out its normal function
142
Explain the components of the Cas9- guide RNA complex
Cas9 is a protein with active sites that can cut the DNA
It forms a complex with a guide RNA with a complementary sequence that can bind to a target gene
By designing the guide RNA, we can choose which gene is cut by Cas9
143
Explain targeted mutation with CRISPR-Cas9
Complex enters nucleus and finds target sequence (complementary to the guide RNA) on the DNA
Cas9 makes a double stranded break in DNA at the target site
DNA enzymes try to repair the cut- resulting in small insertions/ deletions in the gene (no template, causes errors)
- this causes mutated gene
We can provide a specially designed repair template for the enzymes to copy, to create our own gene
144
Two conditions for using targeted mutation to treat genetic disease
Targets only the cells or organs affected
Is not a change to the germ line/ doesn’t affect next generation
145
Example of gene editing for genetic disease
Sickle cell disease
CRISPR-Cas9 used to break a gene (BCL11A) which shuts down gamma genes at birth
Gamma chains help make haemoglobin
146
Sickle cell disease
Red blood cells have sickle shape due to two recessive copies in the HBB gene
147
What is cystic fibrosis caused by?
Mutation to gene which encodes a chloride ion channel
148
Pre-implantation genetic diagnosis
IVF is used to filter out embryos containing a genetic disease
149
Three parent babies
If the faulty gene is on mitochondrial DNA
A donor egg is used- with nucleus destroyed- and parents nucleus is transplanted
Contains donor mitochondrial DNA, and prenatal nuclear DNA
150
How does an embryo begin?
As a small number of totipotent cells
151
Toro potent
Capable of giving rise to any cell type
152
Is trophectoderm totipotent like other embryonic stem cells?
No, it’s pluripotent
153
Pluripotent
Capable of giving rise to several (not any) cell types
154
During development, cells become more ____ and less ____
Specialised
Flexible
155
What is cell polarisation in an embryo?
Cells making right connections with each other
Microvilli develop on outer cells at this stage
156
What do the outer cells of the embryo develop into?
Trophectoderm
157
What happens once an embryonic cell’s fate is determined?
Certain control genes that code for transcription factors become activated
158
Why is it difficult for a cell to switch to a different cell type once it’s fate has been determined?
Once transcription factors are made, they make more, which turn on certain genes to transcribe mRNA for cell-specific proteins
159
What does it mean for a cell to be terminally differentiated?
It has developed into its cell type, fully functioning in the body
160
Genomic equivalence
The theory that all types of differentiated cells contain all the DNA required to build an entire new organism
(All cells contain full genome)
161
Is it easier or harder to create a new cell from the nucleus of a fully differentiated cell than from a less differentiated cell?
Harder - but still possible because of genomic equivalence
162
Where can we get embryonic stem cells? They are ____potent
Harvested from the inner cell mass of mammalian blastocyst embryos
Pluripotent
163
How are iPS cells made? They are ____potent
Induced pluripotent stem cells are made by reprogramming adult skin cells
Pluripotent
164
Adult tissue stem cells are ___potent cells
Multi potent
They can divide without limit
165
Umbilical cord stem cells are ___potent
Multi potent
Stem cells are isolated from blood of umbilical cord, and frozen
166
Why are umbilical cord stem cells less restricted than adult blood stem cells?
They are younger and immature (less differentiated)
167
What disease can umbilical cord stem cells be used to treat?
Leukaemia- where affected cells are somatic
168
What are stem cells in our bodies important for?
Constant renewal of tissues such as skin and blood
169
Haematopoietic stem cells
Where are they found?
Blood stem cells
In the bone marrow
170
Three examples of adult stem cells
Fat, bone and white blood cells
171
A fertilised egg is ___potent
Totipotent (can give rise to all cell types)
172
What separates totipotent, multi potent and pluripotent cells?
Totipotent cells can divide to create an entire organism- including placenta and embryo
Pluripotent cells can divide into all cell types within an organism, but can’t create an entire organism on their own (like totipotent cells can)
Multi potent cells can differentiate into different cell types, but not all
173
What is used to persuade stem cells to develop into different kinds of cells?
Different culture conditions
174
How do we use a virus to correct single gene disorders?
RNA containing the normal allele is inserted into virus (viral RNA)
Virus infects bone marrow cells that have been removed from patient
Viral DNA carrying the normal allele inserts into chromosome
Engineered bone marrow cells are injected into patient
175
Regenerative medicine is based on the idea that _____
Pluripotent stem cells can be used to repair or replace damaged tissues or organs
