Unit 2 Part II Flashcards
(470 cards)
1
Q
a parent is a known carrier of a structural chromosome rearrangement or there is a previous child with a chromosome abnormality
A
familial abnormality
2
Q
ONTD
A
open neural tube defect
3
Q
recurrence risk if you already have one child with ONTD
A
2-5% (multifactorial, genetic component
4
Q
largest portion of abortuses are due to which chromosome abnormality
A
trisomies, followed by 45, X
5
Q
what is the trisomy that causes the most abortuses
A
trisomy 16
6
Q
what percentage of 45, X conceptions spontaneously terminate
A
95%
7
Q
two types of non invasive prenatal tests
A
examination, ultrasound
8
Q
three types of invasive prenatal tests
A
cytogenetics, biochemical, molecular studies
9
Q
this test can: detect multiple pregnancy, determine gestational age, determine the sex, identify possible abnormalities, may indicate further testing is needed
A
ultrasound
10
Q
when is ultrasound usually performed during the pregnancy
A
18 weeks gestation
11
Q
what is a nuchal translucency thickness of 6mm observed by ultrasound associated with
A
Down Syndrome
12
Q
what test is used to detect a cleft lip
A
ultrasound
13
Q
absence of brain caused by severe ONTD
A
anencephaly
14
Q
brain outside of head caused by severe ONTD
A
encephalocele
15
Q
MSAFP
A
maternal serum alpha fetal protein, an albumin produced by fetal liver
16
Q
how is AFP detected in the maternal circulation
A
it crosses the placenta from the fetus into the mother
17
Q
AFP level is likely to be (higher/lower) in a heavy set woman because the assay gives a result in amount per unit volume
A
lower
18
Q
factors that affect MSAFP
A
gestational age (usually do it at 16-18 weeks), mother’s weight, maternal diabetes, diabetic status, race
19
Q
low levels of MSAFP may risk of
A
Down syndrome and other chromosome abnormalities
20
Q
high levels of MSAFP may risk of
A
ONTD
21
Q
maternal serum quad test performed at 15-21 weeks
A
since AFP tests only give risks, combine with other tests to get closer to a diagnosis
22
Q
PAPP test performed at 10-13 weeks, when low, is associated with risk of
A
Down Syndrome
23
Q
non invasive prenatal screening uses _____ for testing
A
cell free placental DNA–free floating DNA comprised of DNA from mother and fetus
24
Q
what percent of the cfpDNA is from fetus
A
about 15%
25
detection of anuesomy using cfpDNA is a (screening/diagnostic) test
screening
26
2 confirming diagnostic tests when the result is out of the normal range for a cfpDNA test
FISH, karyotype analysis performed on amniotic fluid collected by amniocentesis
27
a procedure where a needle is inserted through the abdomen into the amniotic cavity and withdrawing amniotic fluid
amniocentesis
28
at what age is amniocentesis usually performed
16-18 weeks
29
what is the risk of doing amniocentesis early at 13 weeks
less fluid in the cavity, removing fluid can limit the mobility of the fetus, could lead to developmental defects
30
AFAFP
amniotic fluid alpha fetal protein
31
low AFAFP levels indicate
chromosomal abnormalities
32
elevated AFAFP levels indicate
ONTD, MZ twins, fetal death, body wall defect, anencephaly
33
elevated MSAFP levels but not elevated AFAFP levels
DZ twins, small mother
34
closed neural tube defects present as (high/normal/low) AFP levels in mom and amniotic fluid
normal
35
confirmatory test if you see elevated AFP
acetylcholinesterase
36
why would acetylcholinesterase be present in amniotic fluid
if there is a defect in the neural tube
37
confirmatory test if you see low AFP
karyotype analysis
38
CVS testing
chorionic villi sampling
39
risk of fetal loss in CVS testing
1 in 100
40
what does the CVS sample
the placenta
41
how do you confirm abnormal CVS result
amniocentesis
42
if a mosaicism occurs, what makes it possible that CVS will work
the mosaicism must occur in both placental and fetal cells
43
when only part of the placenta has a mutation and the mutation is not in the fetus
confined placental mosaicism
44
implications of CVS testing with a confined fetal mutation mosaic
the CVS testing may miss the mutation
45
when is CVS the method of choice despite risks
if you want to know early on if there is a problem so you have the option to terminate the pregnancy
46
when would a trisomy in an uncle not affect the fetus
if it's a nondisjunction error and not heritable
47
when would a trisomy in an uncle affect the fetus
if there's a Robertsonian translocation and heritable
48
why use polar body analysis
when it is known that one or both partners carry a gene mutation, like with CF. the mutation may be in the polar body, so then you can use the egg. if it's not in the polar body, then it's in the egg, so don't use that egg.
49
preimplantation genetic diagnosis
test the 8 cell stage of the developing embryo--take one cell out and do the general assay to look for chromosomal aneuploidies
50
what to do if mom has known mitochondrial disease
enucleate a donor egg and use donor cytoplasm, mom's nucleus
51
risky prenatal tests
amniocentesis, CVS
52
why would you perform a risky prenatal test
if a parent has a structural abnormality
53
a dizygotic twin pregnancy (does/does not) elevate amniotic fluid alpha fetoprotein
does not
54
prenatal diagnosis (can/cannot) identify males with huntington disease
cannot
55
when do most couples learn that they are both carriers for CF
after they have an affected child
56
tumors such as leukemias are known as ___ tumors
dispersed
57
uncontrolled cell growth characterized by a change in the normal organizational pattern of tissues or cells
malignancy
58
when cells become invasive or migrate to another site
metastasis
59
cancer of mesenchymal tissue (bone, cartilage, muscle, fat)
sarcoma
60
cancer of epitheloid tissues
carcinoma
61
cancer of bone marrow
leukemia
62
cancer of lymph and spleen
lymphoma
63
a primary cancer in a secondary location is known by the __classification
primary
64
gain, loss, or rearrangement of chromosomes
chromosome instability CIN
65
a dominantly acting gene involved in unregulated growth and proliferation
oncogene
66
how are oncogenes carried
by viruses
67
two ways to get an oncogene
mutation of proto-oncogene, from virus
68
structurally important "housekeeping genes" involved in cell proliferation and development
proto oncogene
69
proto oncogenes code for: (five things)
growth factors, cell surface receptors, intracellular signal transduction, DNA binding proteins (transcription), regulation of cell cycle
70
activation of proto-oncogene
mutation to its oncogene potential
71
(gain/loss) of function mutation in proto oncogene tumorigenesis
gain of function
72
number of alleles that must be mutated to activate a proto oncogene
one
73
genetic marker associated with chronic myelogenous leukemia
translocation between chromosome 9 and 22
74
type of translocation involved in chronic myelogenous leukemia
imbalanced--breaks within two genes and gets rearranged, promoter from one gene and coding from another > chimera
75
diagnostic marker of chronic myelogenous leukemia
Philadelphia chromosome
76
what does the 9;22 translocation in chronic myelogenous leukemia produce
an abnormal tyrosine kinase
77
how have negative side effects been minimized in chronic myelogenous leukemia
drug that targets aberrant tyrosine kinase specifically (targeted to a specific genetic lesion)
78
how is acute promyelocytic leukemia detected
FISH probe flanks break point of translocation
79
positive FISH result that indicates acute promyelocytic leukemia
yellow fusion signal
80
genetic element whose loss or inactivation allows the cell to display an alternate phenotype leading to neoplastic growth
tumor suppressor
81
(gain/loss) of function in tumor supressor gene tumorigenesis
loss of function
82
number of alleles that must be mutated to lose function in a tumor suppressor
two (recessive)
83
type of tumor suppressor gene that suppresses tumors by regulating cell cycle or growth inhibition
gate keeper
84
type of tumor suppressor gene that repairs DNA damage and maintains genomic integrity
caretaker
85
why is effect of loss of function of a tumor suppressor indirect
loss of this function may not be directly linked to disease
86
tumor suppressor genes are usually involved in growth of ____ tumors (solid/dispersed)
solid
87
classic gatekeeper mutation, functions in regulation of cell cycle, controls progression from G1 to S
Rb1
88
disease caused by mutation of Rb1 on chromosome 13
retinoblastoma
89
onset of retinoblastoma
prenatal-5 years old
90
sporadic mutations of Rb1 usually result in (uni/bi) lateral retinoblastoma
unilateral
91
inherited mutations of Rb1 often result in (uni/bi) lateral retinoblastoma
bilateral
92
secondary cancer caused by Rb1 mutation
osteosarcoma (teen years)
93
if someone has one mutation inherited for Rb1, it is likely that the second mutation will be (somatic/inherited)
somatic
94
although only a single mutation of Rb1 is inherited, there is a high likelihood that a second mutation will occur, giving rise to a cell with 2 mutations. this gives the pedigree the appearance of dominance, when really the MOI is recessive
Knudson's Two Hit Hypothesis
95
somatic mutations of tumor suppressor genes usually result in (older/younger) age of onset
older
96
familial mutations of tumor suppressor genes usually result in (older/younger) age of onset
younger
97
familial cancer syndrome, mutation of p53, associated with many different cancers
Li Fraumeni
98
why is breast cancer so devastating in males
they have no idea what's happening
99
BRCA mutations are (gatekeeper/caretaker) mutations
caretaker
100
five breakage syndromes
fanconi anemia, bloom syndrome, ataxia telangiectasia, xeroderma pigmentosum, cockayne syndrome
101
moi breakage syndrome
recessive
102
why are breakage syndrome chromes so unstable
they lack DNA repair
103
type of malfunction in hereditary non polyposis colon cancer
MMR
104
indirect testing for hereditary non polyposis colon cancer uses
microsatellites
105
why is testing for hereditary non polyposis colon cancer indirect
don't know where the mutations are
106
why is hereditary non polyposis colon cancer NOT a gene mutation
it is a malfunction in a normal cellular process (MMR) that in and of itself is not deleterious
107
why does Down syndrome increase risk for leukemia
AML gene is located on chromosome 21
108
two problems with allogenic stem cell use
graft v host, immunosuppression
109
NF1
inherited tumor suppressor
110
the stalk domain of influenza haemagglutinin is embedded into:
the surface of the viral capsid
111
two major antigenic proteins in the influenza virus
haemagglutinin and neuraminidase
112
purpose of influenza haemagglutinin
molecular harpoon--how flu virus binds to the surface of cells (via head domain)
113
other viruses that use harpooning mechanisms to gain entry to cells (influenza and....)
HIV, SARS, ebola
114
the mechanism of entry using a molecular harpoon
membrane distortion
115
____ ____ _____ can be developed that specifically target different steps in virus entry by harpooning mechanism
small molecule inhibitors
116
purpose of mirror image peptide
inhibits gp41, the harpoon in HIV
117
degrades proteins
proteasome
118
only functional form of the protein
folded (native) form
119
the information necessary for a protein to fold to its native three dimensional conformation is where
encoded in its amino acid sequence
120
to random coil and back to biologically active structure
reversible denaturation
121
protein is vulnerable to _____ when it is in partially folded conformations because they expose hydrophobic residues that have not yet been buried in the hydrophobic core
aggregation
122
monomeric collapse is driven largely by:
hydrophobic effect
123
folding defects can affect: (2 things)
the properties of N (structure or stability) or the pathway the unfolded molecule takes to reach N (N=native form)
124
hsp60
60 kilo dalton heat shock protein--chaperone
125
how does hsp70 chaperone protein folding
binds to proteins as they are being synthesized by ribosomes and protect against aggregation by covering up sticky hydrophobic pathes
126
how does hsp60 chaperone protein folding
monomers make a large donut, misfolded proteins enter the cavity. In the cavity, ATP hydrolysis is used to physically unfold the misfolded protein. Protein can refold properly while protected inside the cavity
127
type of proteins that require chaperones to fold
large, multidomain proteins
128
unfolding enzyme that combines isolation, forced unfolding, and confinement
GroEL/GroES
129
most common natural substrates for GroEL/GroES
mixed alpha/beta secondary structures
130
ubiquitin/proteasome pathway
regulates protein turnover/degradation
131
role of ubiquitin
targets proteins for degradation by covalent ligation
132
covalent ligation by ubiquitin requires
ATP
133
E (1/2/3) activates ubiquitin in an ATP driven reaction that creates a high energy, covalent, thioester bond
E1
134
E (1/2/3) transfers the activated ubiquitin to the target protein via a thioester intermediate
E2
135
E (1/2/3) catalyzes the final transfer to the epsilon amino group of one or more specific lysine residues on the target protein. Repeated to generate polyubiquitin chains of various lengths
E3
136
core structure of proteasome
double donut
137
regulatory particles on proteasome
caps
138
where polyubiquitinated proteins bind on the proteasome
the cap
139
four types of diseases of the ubiquitin proteasome pathway
cancer, neurodegenerative diseases (AD, Parkinson, HD), CF, autoimmune
140
improper processing of peptide antigens--ubiquitin proteasome pathway defect
autoimmune disease
141
diseases in which ubiquintinated proteins are observed in plaques, Lewy bodies...
neurodegenerative (AD, HD..)
142
diseases in which there is increased degradation of p52, p27
cancers (those are tumor suppressors)
143
a mutation of a residue that is essential for function
direct knockout
144
mutation that pushes the equilibrium toward the unfolded state
destabilization
145
mutation shifts the conformational eqbm to an incorrectly folded state
toxic conformation
146
transcription factor, activated by DNA damage, triggers cell cycle arrest or apoptosis, prevents accumulation of chromosomal mutations
p53
147
where most mutations on p53 are found that cause it to lose function
DNA binding domain
148
Zinc ion role in p53
necessary for site specific DNA binding
149
where does the p53 zinc ion fit into the DNA
minor groove
150
___-___ provides scaffold for helix and loop on p53
beta-clam
151
__ ___ ___ alter side chains that directly bind to DNA and act by reducing DNA binding without changing overall protein structure or stability
DNA contact mutants
152
(stability/contact) mutants do not change DNA binding residues, often very distant from binding site. They decrease thermodynamic stability by disrupting hydrophobic, vdw, electrostatic, H-bond interactions
stability
153
destabilizing mutations often cause proteins to _____
aggregate
154
most common outcome of missense mutations
loss of thermodynamic stability (eqbm constant between native and unfolded/partially folded forms of the protein)
155
why do destabilized p53 mutants accumulate in cancer cells to abnormally high levels
p53 activates transcription of its own E3 ubiquitin ligase, MDM2
156
p53's own E3 ubiquitin ligase
MDM2
157
what is the purpose of the p53 negative feedback loop with MDM2
keeps p53 levels very low in healthy cells with wild type p53
158
how can cancer be treated using p53
restoring proper p53 expression leads to regression of a variety of lymphomas and sarcomas without affecting normal tissues (mouse model)
159
crevice binders
small molecules that stabilize mutant proteins by associating with a specific nook in a protein's native structure
160
crevice binders are (specific/non specific) protein stabilizers
specific
161
small molecule action in blocking the interaction between p53 and MDM2
can bind either MDM2 side or p53 side--suppresses degradation of p53; a rising tide floats all boats--brings the overall p53 activity back up by raising the number, even if individually they don't work that well
162
70% of CF cases are caused by deletion of:
Phe508 in the CF transmembrane conductance regulator
163
CF transmembrane conductance regulator function
gated chloride channel
164
in CF, Phe508 CFTR is (overexpressed/missing) in target tissues
missing
165
structure and function of wild type CFTR and the CFTR missing Phe508 are (similar/different)
similar--the mutant is just missing that one residue and there are a few turns that are different
166
primary defect caused by mutant -Phe508 in CF
alters the pathway by which CFTR folds and assembles
167
family of membrane proteins that CFTR belongs to
ABC transporters (ATP binding cassette)
168
where is protein folding arrested prematurely in the mutant CFTR
ER--which then tags it for degradation by the proteasome
169
treatment options for mutant CFTR
none yet--the proteins fold better at 25C but you're already dead by then...other possibilities: small organic molecules, overexpressing chaperones, inhibiting degradation by ubiquitin-proteasome pathway, stimulating CFTR function
170
serine protease inhibitor
serpin
171
anitrypsin deficiency causes:
emphysema
172
principle target of serpin in anitrypsin
neutrophil elastase
173
where is neutrophil elastase released
sites of inflammation
174
how does unchecked neutrophil elastase activity lead to emphysema
excessive connective tissue damage occurs
175
bind to target protease and prevent it from binding substrate
serpins
176
mechanism of serpin
molecular mousetrap--uses stored energy to trap its target
177
(uncleaved/cleaved) antithrombin has tumor suppressing activity by inhibiting angiogenesis
cleaved
178
(uncleaved/cleaved) antithrombin has protease activity
uncleaved
179
where does the reactive center loop on a1-anitrypsin want to end up after cleaving
on the inside--wants to be a beta strand, not on the outside
180
S-type a1-anitrypsin mutation results in:
protein not being able to H-bond, makes beta sheet more vulnerable to misinsertion
181
how does polymerization of mutant a1-anitrypsin occur in the liver
central beta sheet aberrantly opens and allows part of the reactive loop of a second protein to insert into the lower portion of the sheet
182
insertion of the RCL (reactive center loop) of a1-anitrypsin is (reversible/irreversible)
irreversible--once inserted, it never comes back out
183
how do mutant a1-anitrypsin polymers cause disease in the liver
these polymers cannot be cleared from the liver and accumulate, eventually causing liver failure
184
how can a1-anitrypsin polymer formation be blocked/reversed?
by peptides that correspond to portions of the reactive center loop--they bind the beta sheet where part of the RCL from a second antitrypsin molecule would occupy
185
a group of fatal, progressive, degenerative diseases of the central nervous system by infection with a prion
transmissible spongiform encephalopathies
186
an alternate form of a normal brain protein
prion
187
most definitive test of most neurogenerative diseases
post-mortem staining (reveals amyloid plaques)
188
infectivity of TSE (reduced/not reduced) by irradiation, heat
not reduced
189
infectivity of TSE (reduced/not reduced) by NaOH, other protein denaturants
reduced
190
208 residue glycoprotein of unknown function expressed in brain and many other organs
prion protein
191
soluble, protease sensitive PrP
PrPc, non pathogenic
192
PrPc alpha helix: beta sheet ratio
lots of alpha: little beta
193
PrPsc alpha helix: beta sheet ratio
less alpha: more beta
194
insoluble, protease insensitive PrP
PrPsc
195
the two forms of PrPc and PrPsc interconvert with an eqbm that favors the ___ form
PrPc
196
when several molecules of ____ come in contact (very rare), they can bind via (alpha helix/beta sheet) interaction
PrPsc, beta sheet (blob tag)
197
result of PrPsc blob tag
stabilized beta sheet structure that does not dissociate readily and adds more converted monomers quickly
198
____ studies support protein-only model
transgenic
199
putting purified infectious amyloid protein into mouse
seeding of nucleus
200
why don't we all have TSE's
species barrier
201
what experiment proved the TSE species barrier
infecting healthy hamsters or mice with amyloid fibers taken from diseased hamsters or mice--wild type mouse was immune to hamster amyloid
202
transgenic mouse response to hamster amyloid
normal mouse except it has PrP hamster genes--not immune to hamster amyloid
203
molecular structure that is the culprit of TSE
beta sheet
204
potential therapy for TSE: made chimeric mice using stem cells expressing shRNA against PrPc (lentivirus vector)
siRNA silencing of PrPc
205
three potential therapies for TSE:
siRNA silencing of PrPc, stabilizing PrPc (prevent it from converting to toxic form), immunotherapy
206
how do you generate an immune response to PrP
use a PrP-PrP dimer, generates CD4 and CD8 T cell response in mice
207
what enzyme cleaves APP to yield an Alzheimer AB peptide
secretases
208
correctly cleaved APP eliminates possibility of (AB40/AB42)
AB42
209
Alzheimer plaques: virtually all amyloid fibers are (AB40/AB42)
AB42
210
triplication of the __ gene, either alone or with _____ (chromosomal abnormality), leads to AD
APP, trisomy 21
211
two hypotheses by which AB42 leads to neuronal cell death--what is the toxic species
1-the toxic species is made of small, soluble aggregates of the misfolded peptide that form before the mature fibril
2-the toxic species is the mature amyloid fibril
212
in the hypothesis that states that the toxic species in AD is made of small, soluble aggregates of the misfolded peptide that form before the mature amyloid fibril, what is the role of the amyloid fibril
by product of the disease or may even be protective
213
the structure of AB42 in its amyloid fibril form consists of (a parallel/an antiparallel) beta sheet
parallel in register beta sheet
214
stabilizing interactions in the AB42 beta sheet are (hydrophobic/hydrophilic)
hydrophobic
215
what is the target of Alzheimer treatments
eliminate AB42
216
mutations in (alpha/beta/gamma) secretases are associated with early onset AD
gamma
217
why did modulating gamma secretase activity not work as an effective treatment for AD
gamma secretase cleaves other important stuff
218
how would amyloid fibrils theoretically have a protective role
they would act as a sink for the real toxic species, the pre-fibrillar soluble aggregates
219
why are pigs resistant to diabetes
their islet amyloid polypeptide differs from human IAPP by ten amino acids
220
potential treatment for diabetes
transplantation of pig islet cells
221
structure of islet amyloid polypeptide in aqueous solution
no detectable structure
222
islet amyloid polypeptide is known to bind:
lipid bilayers
223
although islet amyloid polypeptide is structureless, it has ______ tendencies which give a hint about how it interacts with the membrane
helical--a hydrophobic face is apparent
224
how does a peptide inhibit the beta sheet from becoming the amyloid fibrillar state
caps the beta sheet by methylation before it reaches the fiber state--can no longer H bond with nearby side chains or peptides
225
soluble oligomers of IAPP (islet amyloid polypeptide) are (less/more) toxic than mature fibrils
more
226
how do the soluble oligos cause cell death--2 hypotheses
1-disrupts the integrity of the cell membrane--pokes a hole in the membrane which becomes leaky (PORE hypothesis)
2-binds to and stimulates glutamate receptor, leading to dendritic spine loss (RECEPTOR hypothesis)
227
what treatment reverses the physical and cognitive defects caused by soluble oligos in mice
glutamate receptor inhibitors
228
copying DNA into RNA
transcription
229
making RNA usable for protein synthesis
mRNA Processing
230
turning genes on/off
gene regulation
231
(all/not all) DNA is replicated; (all/not all) DNA is transcribed
all is replicated, but not all is transcribed
232
transcription occurs based on
needs of the cell
233
type of RNA that codes for proteins
mRNA
234
type of RNA that forms the core of the ribosome and catalyzes protein synthesis
rRNA
235
type of RNA that regulates gene expression
miRNA
236
type of RNA that serves as adaptors between mRNA and amino acids during protein synthesis
tRNA
237
two ways RNA is different from DNA
uracil, ribose rather than deoxyribose
238
RNA-RNA hybrids that can have catalytic activity
ribozymes
239
RNA-RNA hybrids that can serve a regulatory function
miRNAs
240
substrates for RNA synthesis
rNTPs
241
____ sequences in the DNA tell RNA Pol where to start
promoter
242
____ sequences in the DNA tell RNA Pol where to stop
terminator
243
step of transcription at which cells regulate which proteins are produced and at what rate
initiation
244
three steps of transcription
initiation, elongation, termination
245
two typical promoter sequences in bacterial genes
-35 box, TATA box
246
role of promoter sequences
recruits polymerase and tells it where to begin transcription
247
role of the 3' untranslated region
regulates stability
248
genes can be coded on (only one/either) DNA strand
either
249
transcription (does/does not) require a primer
does not--occurs de novo
250
RNA Pol (has/does not have) exonuclease activity
does not have
251
RNA Pol (I/II/III) transcribes most rRNA genes
RNA Pol I
252
RNA Pol (I/II/III) transcribes protein-coding genes, miRNA genes
RNA Pol II
253
RNA Pol (I/II/III) transcribes tRNA genes, 5S rRNA gene
RNA Pol III
254
antibiotic that targets RNA Pol
rifampin
255
poisonous mushrooms inhibit eurkaryotic RNA Pol (I/II/III)
RNA Pol II
256
mRNA processing occurs (co-transcriptionally/post-transcriptionally)
co-transcriptionally
257
when mRNAs are covalently modified at the ends and undergo RNA splicing
mRNA processing
258
in bacteria, translation occurs (co-transcriptionally/post-transcriptionally)
co-transcriptionally
259
which enzyme recruits RNA processing enzymes
RNA Pol II
260
what is the purpose of the mRNA cap
protects RNA from being degraded
261
what is the purpose of the poly A addition signal
stability during export and translational efficiency
262
5' cap
G nucleotide stuck on end of RNA backwards
263
type of linkage used to put on the 5' cap
5' > 5'
264
poly A tail and 5' cap are (templated/not templated)
not templated
265
proteins that bind 5' cap and 3' poly A tail mediate: (2 things)
export out of nucleus and translation initation
266
junk sequences
introns
267
how are introns removed
splicing
268
difference between primary transcript and mature mRNA
introns have been removed
269
purpose of interrupted eukaryotic genes
expand the repertoire of gene products via alternative splicing, evolutionary diversity
270
what sequences indicate where introns should be removed
cis acting sequences
271
splicing enzymes
snRNPs-small nuclear ribonucleoprotein particles
272
excised intron
lariat RNA fragment
273
snRNPs recognize _____ and then cleave the RNA at the intron-exon borders and covalently link the exons together
cis acting sequences
274
proteins + uracil rich snRNAs
U-snRNPs
275
fate of the lariat
degraded in nucleus
276
unique linkage formed by formation of lariat
2' > 5'
277
syndrome that results from errors in RNA splicing
Progeria syndrome; truncated protein results in devastating disease
278
in prokaryotes, the final amount of protein depends on:
the efficiency of each step of transcription and translation
279
in eurkaryotes, the final amount of protein depends on:
gene regulation--expression is varied based on cell's needs
280
gene regulatory proteins that bind DNA and help regulate transcription
transcription factors
281
bacteria organize genes in ____
operons
282
how are bacterial genes switched on and off
activators/repressors
283
cis-acting sites in bacterial DNA
operators
284
proteins that start transcription of bacterial genes
trans-acting factors
285
what is the purpose of the two-half sites of the DNA binding sites on an activator protein
specificity--just one site wouldn't be specific enough so they homodimerize
286
key structural feature of transcription regulatory proteins
alpha helix/recognition helix
287
purpose of recognition helix on transcription regulatory proteins
side chains interact in the major groove with a series of base pairs
288
DNA site recognition by transcription regulatory proteins is determined by ______ interactions
amino acid- nucleotide base interactions (does not have to unwind the DNA or disrupt base pairing)
289
a tumor suppressor protein whose loss of function mutations lead to a variety of cancers, beta barrel fits in with major groove
p53
290
p53 is a (negative/positive) transcription factor
negative
291
specific p53 amino acid that associates with DNA backbone
Arg
292
purpose of Zn finger in p53 structure
stabilizes the Arg residue
293
purpose of bacterial operon
efficiently make/regulate everything needed for one task (eg make Trp)
294
transcription of the five trp genes in the trp operon from a single promoter results in the formation of a single long transcript called a
polycistronic mRNA
295
when is the trp operon repressed by the repressor
when Trp is present already--why make more
296
the repressor in the trp operon
Trp itself
297
lac operon is repressed normally by
glucose
298
eukaryotic transcription factors are ____-the two main functions are separable
modular
299
two main functions of eukaryotic transcription factors
DNA binding and transcription activation/repression
300
purpose of the DNA binding domain of eukaryotic txn factors
provides specificity
301
purpose of the activator/repression domain of eukaryotic txn factors
provides function
302
risk associated with modular txn factor
fusion of different parts of different factors as a result of chromosomal translocation can result in a novel activity, sometimes with negative consequences (leukemia)
303
regulatory sequences in eukaryotes are called _____ and can be thousands of base pairs away from the promoter
enhancers
304
typical eukaryotic activators work via a large "______ complex" of about 25 proteins
mediator
305
enhancers are found (before/in/after) genes
all three
306
sequences that bind activators
cis acting
307
enhancers are (trans/cis) acting sequences
cis
308
how do enhancers function in a cell-type specific manner
the proteins that bind them are differentially expressed
309
how does overexpression of HOX11 that leads to lymphoblastic leukemia occur
translocation of enhancer region--usually the gene is off, the enhancer turns it on
310
two major types of chromatin modification
covalent histone modifications and ATP dependent nucleosome remodeling
311
which proteins bind to the nucleosome and open up the chromatin so RNA Pol can bind
transcription factors
312
major histone modification that leads to acetylation of Lys on H3 is (activating/repressing)
activating
313
major histone modification that leads to de-acetylation of Lys on H3 is (activating/repressing)
repressing
314
generally histone (acetyltransferases/deacetylases) activate transcription
acetyltransferases
315
generally histone (acetyltransferases/deacetylases) repress transcription
deacetylases
316
eukaryotic gene ____ proteins increase the rate of transcription initiation once bound to DNA
activator
317
two ways activator proteins increase the rate of txn of eukaryotic genes
1- acting directly on the txn machinery
| 2-changing local chromatin structure
318
a special class of ATPases that displace nucleosomes from promoters
chromatin remodeling enzymes
319
txn factors typically control (only one gene/multiple genes)
multiple genes
320
why txn factors can cause side effects of a drug
affects more than just its target gene
321
how can defects in txn programs block differentiation and contribute to cancer development
cell stays in immature state and continues to divide
322
test that measures the abundance of mRNAs in cells or tissues
gene expression profiling (txn profiling)
323
test that can measure relative mRNA levels, monitors hundreds of genes at once
DNA microarray
324
test that is a whole genome sequencing method that can measure the relative abundance of all RNAs made in the cell
RNA-seq
325
unique regulatory region that controls chromatin structure over entire domain
locus of control
326
what causes beta thalassemia (beta globin production is prevented)
deletion of LCR
327
two ways to remind cells of their cell type
1-autoregulation
| 2-epigenetic inheritance via modification of DNA and chromatin
328
when txn factor activates other genes but also its own gene
autoregulation
329
modification of histones (acetylation, methylation)
epigenetic inheritance-chromatin
330
exception to universal genetic code
mitochondria
331
multiple codons code for a single amino acid
degenerate code
332
most hydrophobic aa's are on which side of the genetic code table
left
333
most charged aa's are on which side of the genetic code
right
334
where are polar aa's on the genetic code table
middle
335
how many start codons are there
one
336
how many stop codons are there
three
337
three terms that refer to stop codons
stop, nonsense, termination
338
how many potential reading frames are there for any given nucleic acid
three
339
how do you get a truncated protein from a mutation in translation
a stop codon is formed where there shouldn't be one
340
what is the effect of silent mutations
rate of translation
341
antiparallel triplet of bases which can hydrogen bond to the codon
anticodon
342
tRNA molecule with aa attached to the 3' OH
amino acyl tRNAs
343
enzyme that attaches the aa to the tRNA
amino acyl tRNA synthetases
344
what forms the acceptor or amino acid stem on tRNA
base pairing of 5' and 3' ends of the tRNA molecule
345
suggests that the first two bases of the codon: anticodon interaction are constrained by normal Watson-Crick base pairing but that the requirements for H-bonding at the third base are less stringent
wobble hypothesis
346
the two steps of the rxn catalyzed by aminoacyl tRNA synthetases
1-activation of aa by rxn with ATP to form aminoacyl adenylate
2-reaction of activated aa with 3'-OH of tRNA to form the aminoacyl-tRNA
347
energy cost of rxn catalyzed by aminoacyl tRNA synthetase
2 phosphoanhydride bonds (hydrolysis of ATP and PPi > 2Pi to push reaction forward)
348
the three sites on the ribosome and what they stand for
E-exit
P-peptidyl
A-aminoacyl
349
the mRNA binds to the (large/small) ribosomal subunit
small
350
what happens at the A site
incoming aminoacyl tRNAs attach
351
what happens at the P site
attachment of the peptidyl tRNA
352
what happens at the E site
harbors the spent tRNA prior to releasing it
353
enzyme that catalyzes peptide bond in protein elongation
peptidyl transferase (a ribozyme)
354
step of translation when mRNA binds and is aligned in correct reading frame, initiator aminoacyl tRNA binds, ribosome assembles from subunits
initiation
355
step of translation when aminoacyl tRNA binds and checks codon-anticodon match, new peptide bond is formed growing chain is translocated from A to P, and mRNA is pulled along
elongation
356
step of translation when release factors bound to GTP bind to stop codon in A site
termination
357
role of GTP hydrolysis in translation
releases peptide chain
358
5-10 nucleotide sequence in prokaryotes found 4-7bp's upstream of the relevant AUG
Shine-Delgarno sequence
359
this sequence in prokaryotes is complementary to the 3' end of the 16s rRNA and H-bonds with it, aligning the mRNA
Shine-Delgarno sequence
360
multiple proteins can be translated from the same mRNA after alignment of the ribosome at different Shine-Delgarno sequences within the mRNA
bacteria have polycistronic messages
361
which tRNA is used to start translation
tRNA-met
362
factors that help assemble and disassemble transient translation complexes
initiation factors
363
how does GTP accelerate translation
GTP causes conformational changes in components of the ribosome and its hydrolysis to GDP + Pi forces reactions to be irreversible
364
energy cost of initiation
1 GTP hydrolysis
365
energy cost of elongation per aa added
2 GTP hydrolysis
366
energy cost of releasing polypeptide
1 GTP hydrolysis
367
energy cost of proofreading (wrong tRNA ends up in the ribosome)
2 high energy phosphoanhydride bonds
368
what are stop codons recognized by
release factors
369
what do release factors carry with them
bound-GTP
370
how does binding of the release factor alter the activity of peptidyl transferase
causes it to add H2O instead of an aa to the peptidyl-tRNA, removing the peptide from the tRNA
371
translation proofreading has high (efficiency/fidelity)
fidelity
372
sources of error in translation (2)
1-attachment of wrong aa to the tRNA
| 2-incorrect base pairing of tRNA to codon
373
two stages of translation when proofreading occurs
1-aminoacyl tRNA synthetase
| 2-when aminoacyl-tRNA first binds to A site of ribosome
374
prooreading activity of aminoacyl tRNA synthetase
two active sites--one to recognize correct aa, other to recognize and cleave the incorrect aa (hydrolysis of GTP)
375
energy cost if the wrong tRNA-aa gets into the A site during elongation
one phosphoanhydride bond
376
at which step of translation is translation usually controlled and why
initiation because it is so expensive energetically
377
which translation factor controls initiation
availability of eIF-2
378
what is the action of eIF-2
carries GTP and initiator tRNA to the ribosome
379
(phosphorylation/dephosphorylation) of eIF-2 by specific protein (kinases/phosphatastes) decreases the rate of protein synthesis
phosphorylation by protein kinases decreases the rate of protein synthesis
380
if the eIF-2 GDP is not phosphorylated, what is its normal fate
it is recycled to eIF-2 GTP
381
when eIF-2 GDP is phosphorylated, what is the result
phosphorylation locks eIF-2/eIF-2B complex in the inactive, GDP bound form
382
when does synthesis of globin in reticulocytes occur
only when heme is available for assembly into hemoglobin
383
in the absence of heme, cells activate Heme Controlled Inhibitor which (phosphorylates/dephosphorylates) eIF-2
phosphorylates
384
heme (activates/inhibits) the change from pro-HCI (inactive) to HCI (active)
inhibits
385
protects 5' end of RNA from ribonucleases and allows eukaryotic cells to distinguish between mRNA and other types of RNA
5' cap
386
5' untranslated region often contains sequences important for translational (fidelity/efficiency)
efficiency
387
can contain signal sequences that target the mRNA to be translated at specific places in the cell or to be transported to particular locations within the cell
3' untranslated region
388
poly A tail is added (co/post) transcriptionally
post
389
purpose of poly A tail
stabilizes the 3' end
390
when iron levels are low, ferritin (is/is not) made and transferrin receptor (is/is not) made
ferritin is not made and the transferrin receptor is made
391
when there is excess iron, ferritin (is/is not) made and transferrin receptor (is/is not) made
ferritin is made, transferrin receptor is not made
392
iron response factor
aconitase
393
in the (presence/absence) of iron, aconitase binds to a specific stem-loop structure known as the Iron Response Element present in mRNA
absence of iron
394
how do endogenous siRNAs and miRNAs down regulate translation
by inducing mRNA degradation
395
RNAi
RNA interference--an important way to regulate protein synthesis
396
what happens to dsRNA to achieve RNAi
gets processed to siRNA
397
what happens to the host mRNA translation when cells are infected with poliovirus
host mRNA translation is strongly inhibited
398
dsRNA is a sign of what
viral infection
399
what does dsRNA presence in the cell cause the cell to secrete
interferons
400
what two enzymes are expressed when interferon binds to the surface of cells
1-ribosome-associated protein kinase (phosphorylates eIF-2 and prevents initiation of translation
2-2,5 A synthetase
401
what does 2,5 A Synthetase do
produces unusual polymers of ATP that activate an endoribonuclease that cuts in the middle of both mRNAs (cellular and viral) and rRNAs
402
how does 2,5 A Synthetase slow down protein synthesis (2 ways)
by loss of mRNAs to be translated and the loss of rRNA to make ribosomes
403
how do cells stop the spread of viral infection
they kill themselves or shut down protein synthesis
404
what drives the efficiency of protein synthesis
hydrolysis of co-factor GTP
405
property of mRNA that codes for proteins that are present at constant levels throughout the lifecycle of a cell
long half life
406
most common use of HW equation
find out carrier risk for a recessive disease
407
HW equation
p^2 + 2pq + q^2
408
2pq (>/<) q^2
2pq>>q^2
409
when individuals choose mates that are more like themselves
assortative mating
410
assortative mating leads to more (heterozygosity/homozygosity)
more homozygosity
411
the ratio of heterozygotes (carriers) to homozygotes (affecteds) goes (up/down) as the frequency of the disease decreases
goes up
412
male birth rate for XLR represents (q/q^2)
q
413
female affected rate for XLR is represented by
q^2
414
female carrier rate for XLR is represented by
2pq
415
three no's for HW to apply
no immigration, no mutation, no selection
416
p+q=1 represents (gene frequency/genotypes)
gene frequency
417
P + H + Q = 1 represents (gene frequency/genotypes)
genotypes
418
assume dominants are (heterozygous/homozygous)
heterozygous
419
assume parents of an autosomal recessive:
are both carriers
420
when any individual has an equal chance of mating with any other individual in the population
random mating
421
in theory, HW is achieved (over time/immediately) and is stable
immediately
422
affect of non random mating
increase homozygotes
423
allows uncommon alleles to become homozygous
consanguinity
424
coefficient of selection
s
425
genetic fitness
f
426
genetic fitness f=
1-s
427
the probability of transmitting genes to the next generation and of the survival in that generation to be passed on to the next, in relation to the average probability for the population
fitness
428
dominant lethals (persist/are removed)
are removed
429
small advantage to many carriers, big disadvantage to few homozygotes
heterozygous advantage/balanced selection
430
mutation rate (higher/lower) in mitochondria
higher
431
mutation rate (higher/lower) in Y chromosome
higher
432
equation for rare autosomal dominants mu=
mu= n/2N
433
in mu=n/2N, n=
number of affected patients born to unaffected parents
434
in mu=n/2N, N=
total number of births
435
in mu=n/2N, mu=
mutation rate
436
the same allele that confers an advantage when expressed in early development may be a disadvantage in adulthood
pleiotropy
437
arising by chance in close physical proximity to a gene with selective advantage and increasing in frequency as a result of selection on this neighboring gene
hitch hiking
438
de novo point mutations are more likely to be (maternally/paternally) inherited
paternally
439
two best known microdeletion syndromes
Prader Willi and Angelman
440
(prader willi/angelman) patients are small and hypotonic at birth, but then begin to gain weight rapidly. Developmentally delayed but do well in special ed
prader willi
441
(prader willi/angelman) patients are severely mentally retarded
angelman
442
(karyotype/FISH/population) studies show the cause of the deletion in prader willi and angelman syndromes
population studies
443
for a prader willi patient, the deletion is present on the (maternal/paternal) chromosome 15
paternal
444
for an angelman patient, the deletion is present on the (maternal/paternal) chromosome 15
maternal
445
why does maternal uniparental disomy also cause prader willi as well as paternal deletion
because the paternal information from chromosome 15 is missing
446
inheritance of a chromosome or chromosomes from 1 parent to the exclusion of the other parent
uniparental disomy
447
uniparental disomy (can/cannot) be detected by standard karyotype
cannot-homologs will look alike
448
tests that can determine uniparental disomy
molecular probe technology, microarray
449
duplication of 1 chromosome leading to lack of heterozygosity
uniparental isodisomy
450
2 different chromosomes from the same parent
uniparental heterodisomy
451
the zygote rescue solution to a monosomy is duplication of the one existing chromosome, leading to:
uniparental isodisomy
452
the zygote rescue solution to a trisomy is loss of one of the chromosomes, leading to (three options):
```
biparental heterodisomy--two different ways
uniparental heterodisomy (when zygote deletes the wrong one)
```
453
the differential modification of the maternal and paternal genetic contributions to the zygote resulting in the differential expression of parental alleles during development and in the adult
imprinting
454
imprinting (is/is not) found on all chromosomes
is not
455
methylation involves adding methyl groups to (A/C/T/G) residues in the DNA
cytosine
456
pattern of methylation is (the same/different) between males and females
different
457
imprinting lasts (indefinitely/one generation)
one generation
458
correct methylation pattern is applied during (mitosis/meiosis)
meiosis
459
when some chromosomes in a male gamete retain the female methylation pattern
imprinting failure
460
result of an imprinting failure
one chromosome from each parent but both have female methylation imprint
461
the study of heritable changes in gene function that are not caused by change in the DNA sequence
epigenetics
462
methylation of genes turns them (on/off)
off
463
what is the mechanism of action of methylated DNA to repress transcription
blocks the binding of required co factors and activators
464
hypomethylation of (proto oncogenes/tumor suppressor genes) may cause cancer
proto oncogenes
465
hyper methylation of (proto oncogenes/tumor suppressor genes) may cause cancer
tumor suppressor genes
466
small, non coding RNAs that bind to mRNA to regulate gene expression to prevent translation or interfere with translation
miRNAs
467
(up/down) regulation of miRNA is reported in a number of tumors
down regulation
468
neurodevelopmental disorder, primarily affects females, seizures, variable phenotype, linked to mutations in the MECP2 txn factor
Rett Syndrome
469
normal function of MECP2 txn factor
development of neurons
470
what is disease severity linked to in Rett syndrome
X inactivation
