Final Flashcards
(175 cards)
1
Q
what is a mutation
A
an alteration in nucleotide sequence in genome, any base-pair change in sequence, single base pair substitution, deletion or insertion, major alteration in chromosomal structure
2
Q
where do mutations occur
A
everywhere,Coding/noncoding regions, regulatory sequences,
Promoters, enhancers, splicing signals.
3
Q
what is a point or base substitution
A
change from one base pair to another
4
Q
types of point mutations
A
missense, nonsense, silent, neutral
5
Q
missense mutation
A
changes to a new amino acid (missed the signal)
6
Q
nonsense mutation
A
don’t hear it or make a stop codon prematurely stopped codon
7
Q
silent mutation
A
mutation but it doesn’t change anything down the road
8
Q
neutral mutation
A
mutations in noncoding regions
9
Q
types of base substitutions
A
transitions and transversions
10
Q
what is a transitions
A
pyrimidine replaces pyrimidine and pruine replaces pruine
11
Q
what are transversions
A
purine to pyrimidine
12
Q
frameshift mutation
A
Result from insertions or deletions of nucleotide.
Loss or addition of nucleotide causes shift in reading frame. Change the way in which its read
Frame of triplet reading during translation is altered.
Altered triplets may code for stop codon
13
Q
how many ways can we read double stranded DNA
A
6
14
Q
classifications of mutations
A
loss of funtion dominant dominant negative gain of function supressor
15
Q
loss of functions
A
reduces/eliminates function of gene product. Loss function of the gene
16
Q
null mutations
A
results in complete loss of function.
17
Q
dominant mutations
A
: results in mutant phenotype in diploid organism. Bad alleles can be dominant if it shows its phenotype regardless of the alleles
18
Q
dominant negative mutation
A
one allele may encode inactive gene product—interferes with function.
19
Q
what can a dominant negative mutation lead to
A
haploinsufficiency
20
Q
what is haploinsuffiency
A
one copy of the allele is not enough to sustain life
21
Q
famous loss of function mutation
A
sickle cell anemia
22
Q
gain of function
A
Result in a gene product with enhanced, negative or new functions, usually dominant
23
Q
suppressor mutation
A
Second mutation that reverts or relieves effects of a previous mutation, intragenic and intergenic
24
Q
intragenic
A
occurs within the same gene
25
intergenic
occurs in genome
26
mutation rates
Likelihood that gene will undergo mutation in single generation or single gamete.
Rate is low for all organisms.
Rate varies for gene to gene
27
how to study mutations rates
compare SNPs, see that a newborn has 60 new mutations compared to parents
28
what does the number of mutations depend on in babies
the fathers age at conception
29
how do mutations arise
from replication, DNA polymerase occasionally inserts incorrect nucleotides, bases can take several forms which increases the chance of mispairing during DNA replication
30
replication slippage
DNA polymerase slips or stutters during replication.
Loop occurs in template strand during replication.
More common in repeat sequences (hot spots).
Hot spots for DNA mutation
Contributes to hereditary diseases
Fragile-X, Huntington disease
31
where are mutational hotspots
in genes associated with cancers, hot spots in repeat domains to see if they relate to the cancer, hot spots in areas with lots of repeats
32
tautomer
purines and pyrimidines exist in tauomeric forms- alternates chemical forms
33
tautomeric shifts
can change the bonding strucutre, may lead to permant base pair changes and mutations
34
H bonds in G-C
3
35
H bonds in A-T
2
36
what form in thymine usually in
keto
37
what does thymine go to if a tautomeric shift occurs
enol
38
what happens when thymine is in an enol form
it will now bind to a guaine with 3 bonds
39
what form in cytosine usually in
amino
40
what form in cytosine in when a tautomeric shift occurs
imino
41
what happens when cytosine is in an imino form
bind to adenine with 2 bonds
42
what type of mutations is a tautomeric shift
spontaneous
43
what are transposable elements
D N A sequences that move within and between chromosomes.
Insert themselves into various locations within genome.
Found in all organisms
Their origins are unclear
44
how much of the human genome is TE
45%
45
what do TE contribute to
spontaneous mutation
genetic rearrangements
horizontal transfer of genetic material
46
types of TEs
DNA vsRNA
viral vs non-viral
replicative mechanism vs exision mechanims
47
2 classes of transposition
Class 1: copy and paste
| Class 2: cut and paste
48
Class one
use host RNA pol make RNA intermediate then use reverse transcriptase
49
class 2
no RNA intermediate at all, cut themselves out of genome and put them somewhere else
50
DNA transposons
```
Move their location without going through RNA intermediate stage.
Inverted terminal repeats (ITRs) are located at ends of transposable elements, part of class 2
```
51
what are ITRS for
to be recognized by transposase
52
direct repeats
not part of the trasnposon, foortpring os transpositions
53
cut and paste transposition
cut and paste, binds to both ends of the transposon which consist of inverted repeats, a sequecne of DNA that makes up the target site
54
transposase
encoded by the TE (autonomous) or from another TE (non-autonomous)
55
what is the DNA at the target site
cut in an offset manner, sticky ends
56
what happens after the transposon is ligated to the host
the gaps are filled in
57
what is a retrotransposon
RNA transposable element, main difference is the RNA intermediate, uses reverse transcriptase, makes a copy of itself in RNA, goes to DNA and then inserts itself into a new place
58
how many types of retrotransponsons are there and what are they
2
| LTR and nonLTR
59
LTR transposon
Long terminal repeat, on both sides of the transposon is the LTR in the same orientation, is the control center
60
what makes up the LTRs
U3
R
U5
61
what composes U3
enhancer and promoter sequences
62
what composes R
5' capping sequence and poly A tail
63
what composes U5
dont know, maybe something for adenylation
64
genes in the LTR transposon
gag
| pol
65
what does gag do?
group specific antigen, makes up inner shell of viral coat,
66
what does pol do?
one giant gene that encodes reverse transcriptase, inegrase and protease
67
what does integrase do?
what actually puts the RNA into the genome
68
what does protease do?
cleaves the products of these genes, makes the cut so you have 2 separate enzymes instead of 1
69
where does transcription start for LTR transposons
starts in 5' LTR at the 5' R sequence
70
what enzyme carries out transcription of the LTR trasnpsons
the hosts enzyme
71
where is transcription terminated in the LTR transponson
3' LTR
72
where do the enzymes bind when transcription of the LTR transposons begin
enzymes bind to U3 but transciption starts at R
73
steps for LTR transposition
1. host tRNA base pairs to the primer binding site near the 5' end
2. Reverse transcitpase copies R and U5 sequences into DNA
3. the new DNA sequence can base pair to the R of the 3' LTR
4. the first strand of DNA is then reverse transcribed
5. the RNA template is degraded by RNAse leaving a fragment to prime the second strand DNA synthesis
6. the small 3' fragment is used to make a DNA primer
7. synthesis proceeds in both directions to give double stranded DNA with an LTR (U3,R,U5)
74
what is the tRNA used as
the primer for DNA synthesis by reverse transciptase
75
Steps for non-LTR Transpositions
1. The ORFs are translated by the host’s enzymes. These are read by the host’s ribosomes to make an RNP.
2. The RNPs bind to the additional RNA copies of the transposable element, and place them into stress granules.
3. These stress granules empty the RNP/RNA complexes into the nucleus, where the RNAs are reverse-transcribed and integrated into new regions of the genome.
76
What are LINEs
Long Interspaced Nuclear Elements
77
What are SINEs
Short Interspaced Nuclear Elements
78
What do SINES rely on?
LINEs
79
Basic cancer definition
Genetic disease at the somatic level is characterized by gene products derived from mutated or abnormally expressed genes
80
Genomic Alterations found in cancer cells
Single-nucleotide substitutions
Large-scale chromosome rearrangements
Amplifications and deletions
81
what percentage of cancers are caused by germline mutations
5%
82
2 fundamental properties of cancer cells
proliferation and metastasis
83
proliferation
abnormal cell growth and division
84
metastasis
defects in normal restraints that keep cells from spreading and colonizing other parts of the body
85
benign tumor
The cell loses genetic control over cell growth
Result in multicellular mass
Removed by surgery, causing no serious harm
86
malignant tumor
Cells break loose, enter the bloodstream invade other tissue—form secondary tumors (metastases)—life-threatening
87
clonal origin
All cancer cells in primary and secondary tumors are clonal.
| Clonal: originated from the common ancestral cell that accumulated numerous specific mutations
88
driver mutation
give a growth advantage to tumor cells, Tens of thousands of somatic mutations are present in cancer cells.
Fewer than a dozen mutated genes may be sufficient to create a cancer cell
89
passenger mutation
Have no direct contribution to the cancer phenotype.
90
what is the cancer stem cell hypothesis
Tumor cells that do proliferate give rise to cancer stem cells that have the capacity for self-renewal.
Stem cells are undifferentiated cells with the capacity for self-renewal
91
what does carcinogen mean?
carcino--> cancer gen--> to generate, something that generates cancer, Delay between exposure to carcinogen and appearance of cancer is an indication of a multistep process.
92
tumorigenesis
development of malignant tumor
93
what are the genetic alterations from tumorigenesis
Release cancer stem cells from normal controls
Each step confers a selective advantage to the growth and survival of a cell
Propagated through successive clonal expansion
94
Cancer cells show higher than normal rates of
Mutation.
Chromosomal abnormalities.
Genomic integrity
95
mutator phenotype
High level of genomic instability in cancer cells
Highly improbable that these can revert
Mutate more than the normal mutation rate
96
translocation
swap pieces of DNA causes a disease, in cancer cells its easy to swap the chromosome pieces
97
Genomic instability in cancer cells is characterized by
Somatic point mutations
| chromosomal effects
98
Chromosomal effects
```
Translocations
Aneuploidy
Chromosome loss
DNA amplification
Deletions
```
99
reciprocal translocation
highly prevalent in cancers, both chromosomes swap
100
epigenetics
Study of chromosome-associated changes that affect gene expression but do not alter nucleotide sequence of DNA
Epigenetic effects may be present in somatic or germ-line cells.
101
epigenetic modification examples
DNA methylation, histone acetylation, and phosphorylation
102
what type of DNA do cancer cells have?
altered DNA methylation patterns
103
what are the altered DNA methylation patterns
Less methylation in cancer cells than in normal cells
| Promoters in genes are hypermethylated in cancer cells
104
what is the result of the DNA methylation patterns in cancer cells
repression of transcription
105
what modifications are disrupted in cancer cells
histone modifications
106
what is going on in the histone modifications in cancer cells
Genes that encode histone-modifying enzymes are often mutated or aberrantly expressed in cancer cells.
107
what control do cancer cells lose
cell proliferation control
108
development
the slow process of progressive change in an organism has to do with regeneration
the interface of the genotype and the phenotype
109
embryology
The study of development between fertilization and birth
110
is all developmental biology embryology?
NO
111
what do all organisms arise from
a single cell
112
what are the 3 interrelated processes in embryonic development
Cell division
Cell differentiation
Morphogenesis
113
what is morphogenesis
how to make organs
114
genomic equivalence
All cells in the zygote have the same genome
| indicates that cells need to regulate their genome during development
115
what does differentiation result from
differential gene expression
116
what is cleavage
type of mitosis
mitosis without growth (subdivides the fertilized zygote)\
subdivide one cell into many smaller things
117
what is the goal of cleavage
“Kick-starts” cell differentiation
Polarized Oocytes differentially localize mRNAs and proteins
Maternal Determinants
118
How Can We Make Cells Different During Development
Differential Gene Expression
119
cis regulatory element
Regions of non-coding DNA
Found in the vicinity of the genes that they regulate, on the same strand of DNA
Typically regulate gene expression by binding to transcription factors
120
what are the types of transcription factors
Promoters
Enhancers
Silencers
Insulators
121
what is an insulator
sequences that regulate the level of expression
122
what is a trans regulatory element
Genes that modify the function of distant genes
DNA sequences that encode trans-acting factors
These are usually transcription factors
These are also HIGHLY pleiotropic
123
pleiotropy
one gene = many functions
124
Methods of Differential Gene Expression
enhancer modularity
125
what is enhancer modularity
Enhancers or repressors for a gene “code” for expression in different tissues
126
methylation
Methyl groups can be added to DNA sequences to modify expression
127
what bases can be methylated
cytosine and adenine
128
CpG islands
Methylated regions of the vertebrate genome (CG repeats)
| Often occur in promoters
129
Cis-regulatory elements DO NOT include
TF
130
Trans-regulatory elements include
TF
131
Alternative RNA splicing
a single gene can encode multiple products
| depending on what exons are kept in mRNA you can make different proteins
132
splicing enhancers
promote the assembly of the spliceosome at specific intron/exon boundaries
Introns have lots of information specifically enhancers, DNA sequences but they recruit splicesosome to the middle of the area to splice out the intron
133
ribosomal selectivity
ribosomes show favoritism
Not all ribosomes translate every single mRNA
is how we make cells different from each other
134
gene regulatory networks are a set of
Genes
Proteins
mRNAs
135
what do the parts of gene regulatory networks do
Interact to control a specific function
| Controls transcription and cell signaling
136
what is the gene regulatory network
is the many ways genes interact with each other in a specific cell
137
what are the nodes in the gene regulatory network
gene, protein, or mRNA
138
what are the edges in the gene regulatory network
interactions between the nodes
139
what to GRNs control
animal development
| regulate expression of thousands of genes
140
Can GRNs be homologous
yes
141
what does it mean to be homologous
from the same gene or same common ancestor
142
maternal effect
Offspring’s phenotype of particular trait under control of mother’s nuclear gene products present in egg
Nuclear genes of female gamete are transcribed—genetic products accumulate in egg ooplasm
143
what are stem cells important for?
Important for maintaining tissue homeostasis throughout adult life
significant for the formation of organs
144
how can stem cells be linked to cancer
Mis-regulation of stem cells is linked to multiple cancers
145
what is a stem cell
Gives rise to differentiated cells through cell division, while maintaining its “steminess” (Self-Renewal)
146
what is one way stem cells can exist
in a quiescence state
147
what does it mean to be in a quiescence state
dormant non-proliferative
148
potency
the degree of different cell types a stem cell can generate
149
totipotent
Cell can make anything
| Only the first 4-8 cells are totipotent in humans
150
pluripotent
Can make a few different cell types
151
multipotent
when the stem cells only produce the cell types in the tissues in which they reside
Most adult stem cells in humans
152
how is self renewal achieved
symmetric and asymmetric cell division
153
what is symmetric cell division
Results in either the production of two identical stem cells, or two cells that are committed to differentiate
154
what is asymmetric cell division
Results in a stem cell, and one that is ready to differentiate
Stabilizes the stem cell pool
This is called “Single Stem Cell Asymmetry”
2 daughter cells are not the same
155
what is population asymmetry
Some stem cells are more prone to make cells to differentiate,
While others are prone to make more stem cells.
156
embryonic pluripotent stem cells
modified cell cycle,
157
modifications for embryonic pluripotent stem cell
Shortened G1
G0 Absent
the G1 and G2 phases lengthen
No oscillatory expression of cyclins or CDKs
ESCs are also characterized by a non-functioning G1 checkpoint
158
what cyclin is always on for embryonic pluripotent stem cells and why
cyclin E - Allows for the direct transition from M to Late G1, which is shortened
159
Why would we spend more time in S than G1 and G2 as a stem cell
because stem cells don’t need as much growth since its not specified
160
what do stem cells usually need
a niche
161
whats a niche
is an area of a tissue that provides a specific microenvironment, in which stem cells are present in an undifferentiated and self-renewable state
162
what can cells of the stem cell niche do
interact with the stem cells to maintain them or promote their differentiation
163
Common Mechanisms to Maintain Stem Cells in a Niche
Physcial Mechanisms
Chemical Regulation
intracellular mechanism
164
physcial mechanims
structural and adhesion factors
165
chemical regulation
proteins and hormones secreted from other cells
166
intracellular mechanisms
Cytoplasmic determinants
Transcriptional Regulation
Epigenetic regulation
167
cytoplasmic determinants
movement of these as the cell divides
168
transcriptional regulation
the internal network of transcription factors that silence or maintain specific gene expression
169
epigenetic regulation
chromatin accessibility
170
how is the pluripotency of stem cells maintained after they are harvested
maintained via niche transcription factors
171
what are the trasncription factors important for the niche and mainting the cell pluripotency
Oct4, Sox2 and Nanog
172
are all embryonic stem cells equal in potency
no
| there are 2 pluripotent states of stem cells
173
what are the 2 pluripotent states of stem cells
naive and primed
174
naive
has the greatest potential for pluripotency
175
primed
an ICM cell with some maturation towards the epiblast lineage
