Molecular Flashcards
1
Q
What is a nucleosome
A
2 loops of negatively charged DNA around a positively charged histone
2
Q
What amino acids are histones rich in?
A
Lysine and arginine
3
Q
Which histone ties nucleosome beads together?
A
H1
4
Q
Which histone is the only histone not in the nucleosome core?
A
H1
5
Q
What is orotic aciduria?
A
Autosomal recessive disease with a defect in UMP synthase (defect in de novo pyrimidine synthesis pathway)
6
Q
What would a patient with orotic aciduria have?
A
Increased orotic acid in urine
Megaloblastic anemia
Failure to thrive
7
Q
What is the treatment for orotic aciduria?
A
Oral uridine administration
8
Q
What disease has increased orotic acid with hyperammonemia?
A
OTC deficiency
9
Q
Which nucleotide pairing has 3 H bonds?
A
G-C
10
Q
Which 3 amino acids are necessary for purine synthesis?
A
Glycine
Aspartate
Glutamine
11
Q
What does ribonucleotide reductase do?
A
It converts ribonucleotides to deoxyribonucleotides
12
Q
What drug inhibits ribonucleotide reductase?
A
Hydroxyurea
13
Q
What does HGPRT and PRPP do?
A
Converts guanine to GMP
Converts hypoxanthine to Inosinic acid (IMP)
14
Q
What does APRT and PRPP do?
A
Converts adenine to AMP
15
Q
What does adenosine deaminase do?
A
Converts adenosine to inosine
16
Q
What does xanthine oxidase do?
A
Converts hypoxanthine or xanthine to uric acid
17
Q
What does adenosine deaminase deficiency cause?
A
SCID - prevents DNA synthesis and thus decreases lymphocyte count.
18
Q
What is the inheritance pattern of ADA deficiency?
A
Auto recessive
19
Q
What was the first disease to be treated by experimental human gene therapy?
A
ADA deficiency
20
Q
What is Lesch-Nyhan syndrome?
A
Absence of HGPRT - no purine salvage, excess uric acid, excess de novo purine synthesis.
21
Q
What will a Lesch-Nyhan patient exhibit?
A
Retardation Self-mutilation Gout Hyperuricemia Aggression Choreathetosis
22
Q
What is the inheritance pattern of Lesch-Nyhan syndrome?
A
X-linked
23
Q
What is the severity of damage with point mutations in DNA in descending order?
A
Frame shift
Nonsense
Missense
Silent
24
Q
What is a nonsense mutation?
A
Change resulting in a stop codon
25
What is a missense mutation?
Change resulting in a different amino acid that is similar to the original
26
What is a frame shift mutation?
Change resulting in misreading of all nucleotides downstream
27
How many origins of replication are seen in prokaryotes?
1
28
How many origins of rep are in eukaryotes?
2
29
What does helicase do?
Unwinds DNA at replication fork
30
What do single stranded binding proteins do?
Prevent strands from reannealing
31
What do DNA topoisomerases do?
Create a nick to relieve supercoiling
32
What drugs inhibit DNA topoisomerases?
Fluoroquinolones
33
What does primase do in DNA replication?
Makes an RNA primer for DNA polymerase III to initiate replication
34
What does DNA pol III do?
Adds nucleotides on leading and lagging strands from 3' to 5' using 5' to 3' synthesis
PROKARYOTIC ONLY
35
What does DNA pol I do?
PROKARYOTIC ONLY
| Degrades the RNA primer and replaces it with DNA using 5' to 3' exonuclease
36
What does DNA ligase do?
Catalyzes formation of a phosphodiesterase bond within a strand of double-stranded DNA
37
What does telomerase do?
Adds DNA to 3' ends of chromosomes to avoid loss of genetic material with every duplication
38
What is nucleotide excision repair?
Repairs bulky helix distorting lesions with endonucleases like pyrimidine dimers.
Endonucleases releases the oligonucleotide containing base
39
What disease has a defect in nucleotide excision repair?
Xeroderma pigmentosum - cant repair pyrimidine dimers caused by exposure to UV light
40
What is base excision repair?
Cut DNA at apurinic and a pyrimidine sites, empty sugar is removed, gap is filled and resealed
41
When would base excision repair be used?
To repair spontaneous/toxic deamination
42
What is mismatch repair?
Newly synthesized strand is recognized, mismatched nucleotides are removed and the gap is filled and resealed
43
In what disease is mismatch repair broken?
Hereditary nonpolyposis colorectal cancer
44
In what disease in no homologous end joining mutated?
Ataxia telangectasia
45
What is nonhomologous end joining?
Brings together 2 ends of DNA fragments to repair double stranded breaks
46
In what direction are DNA and RNA synthesized?
5' to 3'
47
What does DNA synthesis require?
The triphosphate bond on the incoming 5' base and a free OH on the 3' base
48
In which direction is mRNA read?
5' to 3'
49
In what direction is protein synthesis?
N to C
50
What is the most abundant type of RNA?
rRNA
51
What is the longest type of RNA?
mRNA
52
What is the mRNA start codon?
AUG
53
What amino acid does the start codon code for?
Methionine in euks
| F-met in proks
54
What are the stop codons?
UGA
UAA
UAG
55
What is the promoter site?
Site where RNA polymerase and multiple other transcription factors bind to DNA upstream from a gene locus.
Rich in A-T
56
What would a mutation in the promoter site result in?
A decrease in the amount of gene transcribed
57
What is the enhancer/silencer?
Stretch of DNA that alters gene expression by binding transcription factors
58
What does RNA pol I do?
Makes rRNA in euks
59
What does RNA pol II do?
Makes mRNA in euks
60
What does RNA pol III do?
Makes tRNA in euks
61
What does alpha-amanitin do?
It is a poison found in Amanita phalloides.
| It inhibits RNA polymerase II - causes hepatotoxicity if ingested.
62
What is the initial transcript in RNA processing?
Heterogenous nuclear RNA
63
Where does RNA processing occur?
In the nucleus
64
What are the post translation modifications to make mRNA?
Capping of 5' end
Polyadenylation tail on 3' end
Splicing out of introns
65
What are the steps of splicing?
1. Make spliceosome with snRNPs and the primary transcript
2. Lariat intermediate made
3. Lariat released to remove intron
66
What patients make antibodies to snRNPs?
Lupus patients
67
What enzyme checks the amino acids binding to the 3' end of tRNA?
Amino-acyl tRNA synthetase
68
Which DNA polymerase has 5' to 3' exonuclease activity?
DNA pol I
69
What kind of exonuclease activity does DNA pol III have?
3' to 5'
70
Which antibiotic class inhibits the binding of aminoacyl-tRNA?
Tetracyclines by binding the 30S subunit
71
What happens if aminoacyl tRNA synthetase recognizes that the tRNA has bound the wrong amino acid?
The bond is hydrolyzed
72
What is protein synthesis initiation activated by?
GTP hydrolysis
73
What catalyze a the peptide bond formation during elongation?
RRNA - ribozymes
74
What does the "A" site of the ribosome do?
It binds to the aminoacyl-tRNA
75
What is the "P" site of the ribosome for?
Accommodating the growing peptide
76
What is the E site for?
Holding th empty tRNA as it exits
77
What recognizes the stop codon?
Release factor
78
What do p53 and hypophosphorylated RB do?
Inhibit the progression from G1-S
79
What are the permanent cells and what cell cycle do they stay in?
Neurons
Skeletal and cardiac muscle cells
RBCs
They stay in G0 and regenerate from stem cells
80
What are the stable cells?
Hepatocytes
Lymphocytes
They enter G1 when stimulated
81
What are the labile cells?
```
Bone marrow
Gut epithelium
Skin
Hair follicles
Germ cells
These are always in G1. Never go to G0
```
82
What cells are rich in RER?
Goblet cells
| Plasma cells
83
What does the smooth ER do?
Steroid synthesis and detox of poisons and drugs
84
What does the RER do?
Synthesize secretory proteins and N-oligosaccharides
85
Which cells are rich in smooth ER?
Hepatocytes
| Cells of the adrenal cortex
86
What does the Golgi apparatus do?
Modifies N-oligosaccharides on asparagine
Adds O-oligosaccharides on serine and threonine
Adds mannose-6-phosphate to proteins for trafficking to lysosomes
87
What is I-cell disease?
Inherited condition where mannose-6-phosphate is not being added to proteins so they don't end up in lysosomes where they belong. They are dumped outside the cell
88
What are the features of I-cell disease?
```
Coarse facial features
Clouded corneas
Restricted joint movement
High plasma levels of Lysosomal enzymes
Often fatal in childhood
```
89
What is COPI?
The retrograde vesicular trafficking protein - tells the protein to go from the Golgi to the ER
90
What is COPII?
The anterograde vesicular trafficking protein telling the proteins to go from the ER to the Golgi
91
What is Clathrin?
It is the vesicular trafficking protein that does receptor-mediated endocytosis .
92
What is the fxn of a peroxisome?
Catabolism of long chain fatty acids and amino acids
93
What is a proteasome?
Barrel-shaped protein complex that degrades damaged or unnecessary proteins tagged for destruction by ubiquitin
94
What is a microtubule?
Tubes of polymerized dimers of alpha and beta Tubulin used for axoplasmic transport and locomotion.
Examples: dynein (retrograde transport from positive to negative end)
Kinesin (anterograde)
95
What is chediak-higashi syndrome?
Mutation in lysosomal trafficking regulator gene - have problems With the microtubule dependent sorting of the endosomal proteins and with lysosomes-phagosome fusion.
96
What is the presentation in chediak-higashi syndrome?
Partial albinism
Pyogenic infections
Peripheral neuropathy
Will see giant granules in the neutrophils
97
What is the structure of cilia?
9 doublets of microtubule
| Axonemal dynein causes bending of the cilium by differential sliding of the doublets
98
What is axonemal dynein?
An ATPase that causes the differential sliding of the doublets so the cilia can bend
99
What is Kartagener's syndrome?
Defect in dynein arm --> immotile cilia
| Male infertility, decreased female fertility, bronchiectasis, recurrent sinusitis
100
What is Kartagener's associated with?
Situs in versus
101
What are intermediate filaments responsible for?
Structure
| Examples: vimentin, desmin,cytokeratins, laming, GFAP
102
What is the most common type of collagen?
I - seen in bone, skin and tendons, dentin, fascia, cornea, late wound repair
103
What is type II collagen found in?
Cartilage, vitreous body, nucleus pulposus
104
What is type III collagen found in?
Reticulin- skin,bvs, uterus, fetal tissue, granulation tissue
105
What is type IV collagen found in?
Basement membrane
106
What disease is there a defect in type III collagen?
Ehlers-Danlos
107
What is the structure of procollagen?
Triple helix of 3 collagen alpha chains bound by hydrogen and disulfide bonds
108
What amino acids are in the alpha chains of collagen?
Glycine, proline, lysine
109
What is required for the hydroxylation of proline and lysine?
Vitamin C
110
What cell makes collagen?
Fibroblasts
111
What happens to procollagen outside of fibroblasts?
The disulfide bonds are cleaved to make insoluble tropocollagen. Then cross-linking between lysine and hydroxylysine via Cu-lysyl oxidase to make collagen fibrils
112
What's osteogenesis imperfecta?
An autosomal dominant gene defect resulting in abnormal type I collagen. Specifically, problems forming the triple helix of procollagen
113
What are the clinical findings in osteogenesis imperfecta?
Multiple fractures
Blue sclera
Hearing loss
Dental problems
114
What is Ehlers-Danlos syndrome?
Problems with the synthesis of collagen causing hyperextensible skin, easy bruising, and hypermobile joints.
Type I and V are most likely to be affected.
Can be auto Dom or recessive
115
What other conditions is Ehlers-Danlos associated with?
Berry aneurysms
Joint dislocation
Organ rupture
116
What is alport syndrome?
X-linked recessive disease resulting in abnormal Type IV collagen
117
What are the clinical findings in Alport syndrome?
Nephritis
Deafness
Ocular disturbances
118
What is elastin?
Stretchy protein rich in proline and glycine
119
What enzyme breaks down elastin?
Elastase
120
What enzyme inhibits elastase?
Alpha1-antitrypsin
121
What disease can be caused by excess elastase activity?
Alpha1- antitrypsin deficiency
122
What is the PCR?
A procedure used to amplify a fragment of DNA.
First, the DNA is denatured, then annealed with premade DNA primer, the elongated with heat stable DNA pol
This process is repeated multiple times for DNA sequence amplification
123
What is the southern blot used for?
Visualizing DNA segments
| DNA is denatured then exposed to radiolabelled DNA probe so that the complementary DNA binds and then it's visualized
124
What is the northern blot used for?
Studying mRNA levels
125
What is the Western blot used for?
Labelled antibody is used to bind relevant protein
126
What is the southwestern blot?
It identifies DNA-binding proteins using oligonucleotide probes
127
What are micro arrays?
Thousands of nucleoli acids sequences are arranged in a grid and then DNA or RNA probes are hybridized to the chip. A scanner identifies the amount of complementary binding
128
What are micro arrays used for?
Gene profiling, forensic analysis, cancer mutation, genetic linkage analysis
Able to detect single nucleotide polymorphisms for a variety of applications.
129
What is enzyme-linked immunosorbent assay?
A rapid immunologic technique testing for antigen-antibody reactivity
Patient's blood sample is probed with antigen (indirect) or antibody (direct) to see if the patient has a certain antibody. The added Ag or Ab is attached to a color-generating enzyme that lights up if they do have it
130
What is the ELISA test used for?
HIV testing. The specificity and sensitivity are 100%
131
What is FISH - fluorescent in situ hybridization?
A fluorescent DNA or RNA probe binds to specific gene site of interest on chromosomes
132
What is FISH used for?
Used for localization of genes and visualization of defects
133
What is the cloning method for DNA?
Isolate the mRNA, exposé to reverse transcriptase to make cDNA.
Insert the cDNA into bacterial plasmids and the bacteria will make it for you
134
What is the Cre-lox system?
Gene modification at different developmental points using an antibiotic controlled promoter
135
What is RNA interference?
Using dsRNA synthesized from mRNA of interest and transferring humans with it. The dsRNA separates in Vigo and promotes degradation of the target mRNA causing decreased expression of that gene
136
What is karytotyping?
A process by which metaphase chromosomes are stained, ordered and numbered so they can be visualized.
Used for looking for chromosomal abnormalities
137
What is an example of co-dominance?
Blood groups A, B, AB
138
What is an example of variable expressivity?
2 patients with neurofibromatosis 1
139
What is an example of incomplete penetrance?
BRCA1 mutation not always resulting in breast or ovarian cancer
140
What is an example of pleiotropy?
PKU causes seemingly unrelated sx
141
What is pleiotropy?
When one gene contributed to multiple phenotypic effects
142
What is imprinting?
Differences in gene expression depending on whether the mutations are maternal or paternal
143
What is an example of imprinting?
Prader-Willi and angelman's syndrome
144
What is an example of anticipation?
Huntington's disease
145
What is an example of loss of heterozygosity?
Retinoblastoma
146
What is a dominant negative mutation?
When a heterozygote produces a nonfunctional altered protein that also prevents the normal gene from functioning
147
What is linkage disequilibrium?
The tendency for certain alleles at 2 linked loci to occur together more often than expected by chance
148
What is mosaicism?
When cells in the body differ in genetic makeup due to post fertilization loss of change of genetic info during mitosis
149
What is locus heterogeneity?
When mutations at different loci produce the same phenotype
150
What is an example of locus heterogeneity?
Marfan's syndrome
Homocystinuria
Albinism
151
What is heteroplasmy?
Presence of both normal and mutated mtDNA causing a mitochondrial inherited disease of variable expression
152
Where was the error with heterodisomy?
Meiosis I
153
Where was the error in isodisomy?
In meiosis II or post zygotes duplication
154
When should you consider uniparental disomy?
When's patient presents with an autosomal recessive disorder but there is only one carrier
155
What are the Hardy Weinberg laws?
No mutation occurring at the locus
Random mating
No selection for any of the genotypes
No migration
156
What is the frequency of an X-linked recessive disease in males and females using he hardy-Weinberg equation?
```
Males= q
Females = q2
```
157
What is Prader-Willi syndrome?
An imprinting error in the parental allele causing it not to be expressed
Chromosome 15 inactivation
158
What are the clinical findings of Prader-Willi syndrome?
```
Mental retardation
Hyperphagia
Obesity
Hypogonadism
Hypotonia
```
159
What is Angelman's syndrome?
An imprinting error where the maternal allele is not expressed
Chromosome 15
160
What are the clinical findings of Angelman's syndrome?
Mental retardation
Seizures
Ataxia
Inappropriate laughter
161
What percent chance do 2 carrier parents of an auto recessive disease have of having a child with the disease?
25%
162
What is the pattern of inheritance of CF?
Autosomal recessive
163
What is the mutation if CF?
Defect in CFTR on ch. 7
| CFTR channel actively secretes Cl- in lungs and GI tract and actively resorts Cl- from sweat.
164
What are the clinical findings of CF?
Abnormally thick mucus of the lungs, pancreas, liver
Recurrent pulmonary infections
Chronic bronchitis, brochiectasis, pancreatic insufficiency
Nasal polyps
Meconium ileus
Infertility in males from absent Vas deferens
165
What is the test for CF?
Chloride sweat test. Positive if there is increased concentration of chloride
166
What is the most common lethal genetic disease of the white population?
CF
167
What is the second most common cause of genetic mental retardation?
Fragile X syndrome
168
What is the defect in Fragile X syndrome?
X linked defect in the FMR1 gene
169
What are the clinical findings in Fragile X syndrome?
Marcoorchidism
Long face with a large jaw and large diverted ears
Autism
MVP
170
What are the trinucleotide repeat expansion diseases?
Huntington's disease (CAG)
Myotonic dystrophy (CTG)
Friedrich's ataxia (GAA)
Fragile X syndrome (CGG)
171
What is the most common genetic cause of mental retardation?
Down's syndrome
172
What are the clinical findings in Down's syndrome?
```
Flat facies
Single simian palmar crease
Prominent epicanthal folds
Duodenal atresia
Gap between 1st 2 toes
Congenital heart disease
```
173
What is Down's syndrome associated with?
Increased risk of ALL
| Alzheimer's over 35 yo
174
What is the chromosomal abnormality of Down's syndrome due to?
Meiosis nondisjunction associated with increased maternal age
4% due to Robertsonian translocation
1% due to mosaicism
175
What are the results of the pregnancy quad screen in Down's syndrome?
Decreased alpha-fetoprotein
Decreased estriol
Increased inhibin A
Increased beta-HCG
176
What does the ultrasound show in Down's syndrome?
Increased nuchal? In first trimester lucency
177
What is Edwards syndrome?
Trisomy 18
Most common trisomy resulting in live birth after Down's syndrome
Death within the first year
178
What are the clinical findings of Edwards syndrome?
```
Severe mental retardation
Rocker bottom feet
Micrognathia
Low set ears
Prominent occiput
Congenital heart disease
```
179
What are the results of pregnancy quad screen in Edwards syndrome?
Decreased alpha-fetoprotein
Decreased beta-HCG
Decreased estriol
Normal inhibin A
180
What is Patau's syndrome?
Trisomy 13
181
What are the clinical findings in Patau's?
```
severe mental retardation
Rocker bottom feet
Microphthalmia
Microcephaly
Cleft palate
Holoprosencephaly
Polydactyly
Congenital heart disease
Death within the first years
```
182
What are the pregnancy quad test results of Patau's?
Decreased beta-HCG
Decreased PAPP-A
Increased nuchal translucency
183
What is the Robertsonian translocation?
Occurs when the long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms lost.
184
What is cri-du-chat syndrome?
Congenital micro deletion of the short arm of chromosome 5
185
What are the clinical findings of cri du chat syndrome?
```
Microcephaly
Mental retardation
High-pitched crying/mewing
Epicanthal folds
Cardiac abnormalities (VSD)
```
186
What is Williams syndrome?
Congenital microdeletion of long arm of chromosome 7 including the elastin gene
187
What are the clinical findings of Williams's syndrome?
```
Elfin facies
Intellectual disability
Hypercalcemia (more sensitivity to vit D)
Well developed verbal skills
Extreme friendliness with strangers
CV problems
```
188
What are the features of 22q11 deletion syndromes?
```
Cleft palate
Abnormal facies
Thymic aplasia
Cardiac defects
Hypocalcemia
```
189
What is velocardiofacial syndrome?
Palate, facial and cardiac defects
| 22q11 deletion syndrome
190
What is DiGeorge syndrome?
Thymic, parathyroid, and cardiac defects
191
What is the the result of 22q11 deletion syndrome?
Aberrant development of 3rd and 4th bronchial pouches
