Genetics Flashcards
1
Q
Silent mutations are:
A
Different codon but the same, intended AA
2
Q
Missense mutation
A
Intended AA changed; results may vary
3
Q
Nonsense mutation
A
Intended AA changed to a stop codon
4
Q
Frameshift mutation
A
1 or more nucleotide added/removed
5
Q
What 3 things happen to convert pre-mRNA to mature mRNA?
A
Splicing, poly A tail, and 5’ cap
6
Q
How does mRNA processing differ in prokaryotes?
A
They don’t have RNA processing
7
Q
AZT is a chain ____________. How does it work?
A
Terminator
It does not have a 3’ hydroxyl so when it gets incorporated it will not allow another base to add onto it
8
Q
Ara-C is what type of inhibitor
A
It’s a competitive inhibitor for DNA polymerase
9
Q
Xeroderma Pigmentosum individuals are sensitive to ________
A
Sunlight
10
Q
Xeroderma pigmentosum individuals are prone to developing what 2 things?
A
Melanomas and squamous cell carcinomas
11
Q
Xeroderma pigmentosum is caused by a defect in _________________ which causes the accumulation of _____________ in their DNA
A
Nucleotide excision repair
Thymine dimers
12
Q
What are the main 3 symptoms of cockayne syndrome
A
Developmental and neurological delay
Sensitivity to sun
Progeria
13
Q
Cockayne syndrome has a defect in what repair pathway
A
Transcription coupled repair
14
Q
Why is reverse transcriptase special?
A
It was previously thought that DNA –> RNA and there was no back track
15
Q
GC base pairs have __ h bonds while AT only have __
A
3, 2
16
Q
Histones are ________ that form _____ h bonds with DNA to form a ___________
A
Octamers, 142, nucleosome
17
Q
Histones _________ highly conserved among species
A
Are
18
Q
Approximately _____ % of histones primary structure are made up of positively charged AA ( ________ & __________)
A
20, Lys, Arg
19
Q
The two classes of DNA binding proteins are histones and ____________
A
Transcription factors
20
Q
Protein + DNA = ____________
A
Chromatin
21
Q
_______chromatin is the active form of DNA and is transcriptionally _________.
A
Eu, active
22
Q
Approximately __% of the genome is euchromatin
A
92
23
Q
Transcriptionally inactive DNA is called ______________
A
Heterochromatin
24
Q
What is the position effect?
A
The activity of a gene depends on it’s position in the chromosome. Actively expressed genes will be silenced if relocated near heterochromatin
25
In 1953, Watson and Crick describe _________________________
Double helical structure of DNA
26
In 1966, the ______ _________ was discovered
Genetic code (codon table)
27
The human genome project made ___ cop(ies)y of the genome and cost around ________
1 copy of the 23 chromosomes
| 1B
28
miRNA is important because it can ___________
Interfere with the translation of proteins by binding to complimentary strands
29
miRNA is made by enzymes called ________
Dicers
30
________ ____ _________ gives out exons the ability to recombine into different mature proteins
Alternative RNA splicing
31
Introns begin with _ _ and end with _ _
GT, AG
32
There are approximately ___ splice alternatives for each gene
2
33
When a histone is __________ it is transcriptionally inactive
Deacetylated
34
_____________ histones are transcriptionally active.
Acetylated
35
Acetyl groups are added to histones by _________ and removed by ___________
```
Histone acetyl transferase (HAT)
Histone deacetylase (HDAC)
```
36
Binding of a ligand to PXR causes it to become _________. How is this done?
Active
When a ligand binds to PXR there is a conformational change which causes the corepressor to come off the PXR/RXR complex and the coactivator binds and transcription begins
37
What are the big histone post-translational modifications (5) that we mentioned?
Methylation, acetylation, phosphorylation, ubiquitinylation, SUMOylation
38
Methyl groups are directed added to what nitrogenous bases
C and A
39
Directly methylated DNA has what effect
Repression
40
DNA is read __ to __ but is synthesized __ to __
3-->5, 5-->3
41
What protein unwinds DNA into ssDNA?
DNA helicase
42
What keeps the ssDNA from coiling on itself?
Single-stranded DNA binding protein
43
UV radiation most often causes what? How are they repaired?
Thymine dimers, NER
44
What are the two types of spontaneous DNA damage?
Depurination, guanine/adenine are completely removed from the 1' site of the sugar
Deamination, cytosine loses an amine group and becomes uracil
45
Spontaneous DNA damage results in
Depends on whether the correct or incorrect strand is used as the template during repair
46
Methylation of CpG islands can potentially _______ genes that are essential for the __________ process
Silence, repair
47
When 5-methyl cytosine is deaminated it forms ________. This accounts for 1/3 of all point mutations associated with inherited human disease.
Thymine
48
________ found in well done meats can be converted from a __________________ to a __________________ by out metabolism
Benzopyrene, pro-carcinogen, carcinogen
49
Hereditary nonpolyposis colorectal cancers are caused by what repair mechanism
Mismatch excision repair
50
BRCA1/2 breast cancer is associated with a defect in what repair mechanism
Recombination repair
51
Fanconi anemia is associated with
DNA interstran cross-link repair
52
Incorrect bases in base excision repair are recognized by what enzymes
DNA glycosylases
53
Errors in DNA bases are removed by __________ during base excision repair. The __________ bond is cut by AP endonucleases and _________ removes the deoxyribose phosphate
DNA glycosylase, phosphodiester, AP lyase
54
After a base has been excised (base excision repair) the correct base is added by _________________ and _______________ seals the DNA again
DNA polymerase beta, DNA ligase
55
Familial colorectal cancer assumes the pattern of being ________ __________
Autosomal dominant
56
What enzyme is permanently stalled at sites of damage in Cockayne syndrome?
RNA polymerase
57
Some new drugs have shown promise in cancer, Alzheimer's, and RA, they don't allow histones to be transcriptionally active by inhibiting what enzyme?
HAT
58
HDAC inhibitors have shown promise in anti-convulsives and anti-cancer. What do they do? What kinds of genes would these be important in?
They do not allow histones to be deacetylated
| Especially important in repair mechanisms as to prevent cancers
59
____________ is a drug that inhibits bacterial RNA synthesis but also increases the amount of CytP450 expressed in the liver cells. What is the effect of this upregulation?
Rifampicin, other drugs are metabolized more quickly causing faster clearance
60
What are the symptoms of rifampicin use?
Red color to urine, sweat, and tears (blood, sweat, and tears)
61
Rifampicin interacts with what 2 categories of drugs the most?
Contraceptives and anticoagulants
62
What are the 5 main epigenetic mechanisms?
```
Developmental stage
Environmental chemicals
Drugs
Aging
Diet
```
63
The most active AA in ubiquitin is _______
Lysine, Lys, or K
64
What portion of ubiquitin is connected to lysine residues?
GG (2 aspartates)
65
Where does transcription occur in Eukaryotes?
Nucleus
66
Where does translation occur in eukaryotes?
Depends on whether the protein is going to be in the cytosol (made on free ribosomes) or secreted/incorporated in a membrane (RER)
67
Proteins are synthesized from __ terminus to ___ terminus
N, C
68
The mRNA strand is like the __________ strand but ___ is replaced with ____
Coding, T, U
69
_ _ _ is the start codon in eukaryotes. _______ is the start codon in prokaryotes
AUG, met
| Fmet
69
Sickle cell anemia arises when ___ is incorrectly inserted instead of _____
Val, Glu
70
Sickle cell anemia results from an error in what subunit?
HBB (human beta globin)
71
Duchenne MD results from large _________ and ___________ deletions to ___________
In-frame, out-of-frame, the dystrophin gene
72
Muscle is replaced with what in Duchenne MD? What is elevated?
Fat and fibroid, elevated CK
73
______________ deletions cause a milder form of Duchenne MD, which is called __________ MD
In-frame, Becker
74
tRNA must be activated with ________ which is catalyzed by ____________________
ATP, aminoacyl-tRNA synthetase
75
The prokaryotic ribosome is made of two units _______ and ______ giving it a total sediment coefficient of ______
30, 50, and 70
76
The eukaryotic ribosome is made of a ______ subunit, a _______ subunit, and a total of ____________
40, 60, 80
77
The three sites in the ribosome are:
The acceptor site, the peptidyl site, and the empty/exit site
78
What is required for eukaryotic initiation of translation?
5' cap, polyA tail, Kozak sequence, and ATP dependent mRNA
79
What is the shine delgarno sequence?
The prokaryotic signal (AGGAGG) to begin initiation
80
The pre-initiator complex has 3 main events
1. GTP-bound-initiator-tRNA attaches to small subunit
2. IF in pro and eIF in euk attach to the small subunit
3. The large subunit meets with this complex, GTP is cleaved from IF-GTP complex, and translation begins
81
Streptomycin binds to the ______ subunit of ___________. What does this prevent?
30s (16s rRNA), prokaryotes, prevents assembly of the initiation complex
82
What are the energy requirements for adding an AA to a chain?
1 ATP to activate the tRNA
2 GTP, one on the elongation factor and one to translocate the tRNA in the ribosome
2 GTP for each protein (1 for association of complete ribosome and 1 for the dissociation of the ribosome)
83
What transfers AA to the incoming AA (still attached to original tRNA)?
Peptidyl transferase
84
What is the MoA of tetracycline?
Binds to the 30s subunit and prevents entry of tRNA to ribosome
85
What is the MoA of chloramphenicol?
It inhibits both pro and mito peptidyl transferase
86
Clindamycin and erythromycin bind to what?
The 50s subunit and block translocation of the ribosome
87
Erythromycin is commonly used to treat what?
Pertussis or whooping cough
88
Cycloheximide inhibits _________
Peptidyl transferase in euk
89
Diphtheria toxin inactivates _______________ which interferes with _________________
GTP bound eEF-2, ribosomal translocation
90
Shiga toxin and ricin both bind to ___________ which does what?
The 60s subunit, which blocks entry of aminoacyl-tRNA
91
Tetracycline is analogous to what?
Shiga toxin and Ricin. Tetracycline blocks entry of tRNA by binding to the large subunit in pro, while Shiga and Ricin bind to the large subunit in euk and also block tRNA entry
92
Chloramphenicol is analogous to what?
Cycloheximide, they both block peptidyl transferases
93
Diphtheria toxin is analogous to what?
Clindamycin and erythromycin because they all block ribosomal translocation
94
What does puromycin do?
It is a premature chain terminator in translation. It is resistant to hydrolysis so it blocks ribosomal action
95
What happens when a release factor is loaded?
tRNA dissociates, polypeptide chain is freed, ribosome complexes dissociate, and mRNA is released
96
What is the signal for proteins destined for the cytoplasm?
None
97
What is the signal for proteins destined for the nucleus?
KKKRK
98
What is the signal for proteins destined for the membranes?
N-terminal a polar region (stop-transfer sequence)
99
What is the signal for mitochondrial proteins? What does it allow?
N terminal hydrophobic alpha helix, allows interaction with chaperone proteins
100
Where do proteins get glycosylated?
In the ER as they are synthesized
101
How long is the ER targeting signal peptide?
15-60 AA and has 1 or 2 basic AA and a hydrophobic sequence of 10-15 AA
102
What causes I-cell disease?
Lysosomal proteins are not tagged with mannose 6p so they are found in high levels in the plasma
103
Protein folding is done by what major class? What is the name of the barrel shaped protein? What do chaperonins require?
Chaperones, chaperonins, ATP
104
Alzheimer's is due to _________ of __________ ___________ protein
Misfolding, amyloid precursor
105
Supplementation of __________ has been shown to help with Alzheimer's
Lysine
106
Creutzfeldt-Jakob aka ____________ is due to _______________
Mad cow disease or Kuru, prions
107
The most common glycosylation site is
N-linked on the -NH of Asn
108
What are the two types of glycosylation sites and what amino acids do they affect?
```
O linked (Ser and Thr)
N linked (Asn)
```
109
Over glycosylation can be done to what body part in what condition?
Eye lens, diabetes
110
Parkinson's results from ______________________ which aggregate to form __________. This reduces the availability of ____________
Mutated alpha-synuclein aggregates, Lewy bodies, dopamine
111
Huntington disease is a mutation in the ________ gene. What does this cause?
Huntingtin, this causes repetition of CAG triplet and the over-incorporation of Gln. This forms aggregates
112
_________ are segments of DNA in a chromosome
Genes
113
Location that a gene occupies
Locus or loci
114
Chromatid
One of the two identical copies of a chromosome
115
Centromere
Connects identical sister chromatids
116
___________ region at the end of a chromosome for stability
Telomere
117
__________ is a condition in which cells from a patient have different genotypes or karyotypes
Mosaicism
118
Down syndrome has a trisomy at chromosome __
21
119
Klinefelter syndrome has what two mosaicisms
Some 46XY; some 47XXY
120
Turner syndrome has what mosaicism:
46XX; some 45XO
121
__________ is called X-inactivation and happens _____________
Lyonization, randomly
122
_______________ is the failure of one or more pairs of homologous chromosomes to separate normally during division
Non-disjunction
123
There are 3 types of non-disjunction. What are they?
1 in meiosis I
1 in meiosis II
1 in mitosis early in embryology
124
____________ is the cells with abnormal chromosome number
Aneuploid
125
Are methylated genes up or down regulated? Can this be inherited?
Down, yes
126
How is genetic information used?
1. pedigree analysis
2. Gene defect
3. Molecular diagnosis
4. Personalized medicine
5. Population genetics
127
____________ is the first diagnosed person in the pedigree
Proband
128
What is a feature of autosomal dominant in a pedigree?
Affected children have an affected parent
| Does not prefer one sex over the other
129
What is a feature of autosomal recessive pedigrees?
Affected individuals have normal parents
| Increased occurrence in consanguineous mating
130
Why are females protected from x-linked recessive?
Lyonization of X chromosome
131
What is penetrance? What is one example of a disease with less than 100% penetrance?
The percentage of individuals with a disease genotype that don't show the disease phenotype
Retinoblastoma
132
Traits in which variation is thought to be caused by the combined effect of genes are called _______________
Polygenic
133
When environmental factors cause variation in a trait it is said to be ____________
Multifactorial
134
What is locus heterogeneity?
When a single disorder is caused by mutations at different chromosomal loci
135
Each nucleosome core particle is a complex of ____ histone proteins
8
136
Cytosine can be spontaneously delaminated to what base?
Uracil
137
Intercalating agents such as thalidomide cause what to happen?
They insert in between nitrogenous bases and cause frame shifts during DNA replication
138
________________ repair defects cause BRCA1/2 breast cancer
Recombination
139
Ataxia telangiectasia (AT) causes leukemia, lymphoma, gamma ray sensitivity, and genome instability. What repair pathway is affected? What kind of damage activates it?
ATM protein, a protein kinase activated by dsDNA breaks
140
What are the two types of dsDNA repair? How do they work?
1. Non-homologous end joining - after an accidental double break the protruding pieces are clipped to where both sides are flush and then pushed together (you lose whatever nucleotides were present in the "overhang")
2. Homologous recombination - again dsDNA break happens but this time, a sister chromatid is used as a template to repair and replace the the nucleotides
141
What protein is affected in Cockayne syndrome?
RNA polymerase is permanently stalled at sites of damage
142
HDAC inhibitors stop the removal of acetyl groups from histones, which allows the genes to remain transcriptionally active, what are 2 HDAC inhibitors?
Vorinostat and Entinostat
143
How do sickle cell RBCs differ from WT RBCs?
Sickle cell RBCs lost their disc shape so they are not able to fold and bend to get through capillaries and have a poor oxygen carrying capacity
144
What initiator do prokaryotes use? Eukaryotes? What initiating factor do they use?
Pro- n-formyl-methionine
Euk - methionine
Pro - IF
Euk - eIF
145
Hypophosphatemia follows which inheritance pattern? What does this cause? How do you treat it?
X-linked dominant
Low P in blood due to deficient reabsorption in kidneys, softening of bones due to poor absorption of Ca in intestines, vit D metabolism problems
Treated with oral phosphate and vitamin D
