Midterm 2 Flashcards
(286 cards)
1
Q
human somatic cells are
A
DIPLOID
2
Q
how many chromosomes do human somatic cells have
A
46 chromosomes
3
Q
describe further the 46 chrosomes
A
22 pairs of autosomes and 1 pair of sex cells
4
Q
how many chromosomes do human gamets have
A
23 chromosmes each
5
Q
what is the same as haploid set
A
monoploid set
6
Q
homologous chromosomes have the same ___ But different _____ of those ___
A
homologous chromosomes have same genes but may have different alleles of those genes
7
Q
on average how much do homologous chromoses differ
A
they differ from each other about 1 per 1000 bps, just as any two people
8
Q
sister chromatids are the
A
two double strands that result from one round of semi-conservative DNA replication
9
Q
sister chromatids are highly likely to be
A
100% identical to each other
10
Q
what is a chromosome
A
is a DNA containing structure containing a centromere
11
Q
what is a chromtid
A
a double stranded DNA molecule (plus protein )
12
Q
what are sister chromatids
A
two copies of the same double stranded DNA molecule joined by a centromere
13
Q
where are homologous chromosomes found
A
in diploid cells
14
Q
what is mitosis
A
a diploid somatic cell replicates its DNA once and divided once to form 2 diploid genetically identical daughter cells
15
Q
G1 phase of Mitosis
A
the cell contains two pairs of homologous chromosomes
16
Q
S phase mitosis
A
DNA replication creates identical sister chromatids for each chromosome
17
Q
metaphase fo mitosis
A
chromosomes align randomly along the metaphase plate with the aid of mitotic spindle
18
Q
telophase in mitosis
A
two daughter cells are produces by mitosis –> sister chromatid seperation to form daughter chromosmes
19
Q
mitotic cell cycle phases
A
G1, G0, S, G2, M phase
20
Q
what is the G1 phase
A
active gene expression and cell activity, preparation for DNA synthesis
21
Q
what is the S phase
A
DNA replication and chromosome duplication
22
Q
G2 phase
A
preparation for cell division
23
Q
M phase
A
cell division Mitosis and meiosis
24
Q
G0 phase
A
terminal differential and arrest of cell division
25
G0 phase can lead to
cell remaining specialized but not dividing, eventual cell death (apoptosis)
26
mitosis creates
geneticaly identical daughter cells (although one of them might have a new muation
27
Mitosis definition
a diploid somatic cell replicates its DNA once and divides once to form 2 diploid genetically identical daughter cells
28
Meiosis definition
a diploid germline stem cell replicates its DNA one and divided twice to form 4 haploid cellls that are not genetically identical
29
what is in the cell at the beginning of meiosis
homologous pair: two copies of chromosome 1, one from mom and one from pap
30
human females arrest where in meiosis untill menstration
after crossing over but before disjunction
31
where does crossing over occur in Meiosis
prophase of meiosis 1
32
What are fine-scale mutations? Provide some examples
involve less than 1000 BPs; single base pair is changed
ex: substitutions, deletions, insertions, duplications
33
substitution mutations
replace/substitute a base pair
34
Single base-pair substituations are often called ______ _________
point mutations
35
insertions
add BP
36
deletion
delete BP
37
duplication
add BP (repeated)
38
What is a silent mutation? What are they also called?
changes a codon, but not the encoded amino acid
also called synonymous mutation
39
What is a missense mutation?
changes the encoded amino acidW
40
What is a nonsense mutation?
an amino-encoding codon becomes a stop codon
41
What is a frameshift mutation?
insertion or deletion of a base(s) changes the reading frame
42
What are examples of spontaneous mutations?
mistakes (e.g. replication errors, recombination errors) and endogenous DNA damage
43
What are REPLICATION errors?
polymerase misincorporation, strand slippage in repeated regions
44
What are recombination errors?
unequal crossing over, etc.
45
What are two examples of endogenous DNA damage?
spontaneous base damage, byproducts of metabolism
46
What are examples of spontaneous base damage?
deaminations, depurinations
47
What byproducts of metabolism damages DNA?
oxygen radicals
48
A good polymerase domain has a misincorporation rate of __________.
1/100,000
49
Any misincorporations are clipped off with _____% efficiency by the proofreading activity of the ___________.
99%, polymerase
50
What is DNA mismatch repair?
removes mismatches bases in DNA with 99.9% accuracy
chooses to repair the newly replicated strand; carried out by multi-protein complex
51
About ___ mismatch error per ______ ______ _______ is not detected.
1 per human cell division
52
deamination of cytosine
water attacks cytosine (removes C's amine group) and replaces it with a double-bonded O (carbonyl group)
--> creates URACIL
NOTE: there is no CH3 at the 5 position on either C or U (therefore turns deamination coverts to U)
53
deamination of 5-Me-Cytosine
water attacks cytosine (removes C's amine group) and replaces it with a double-bonded O (carbonyl group)
--> creates THYMINE
NOTE: 5-Me-Cytosine has a methyl at 5 position, T also has CH3 at 5 position (that's the reason why the deamination turns into T rather than U)
54
What's the difference between cytosine and 5-Me-Cytosine?
there's a CH3 (methyl) at the 5th position on the carbon ring!!!
55
___________ _____________ are caused by exogenous (_________) sources of DNA damage.
induced mutations, outside
56
What are sources of exogenous DNA damange?
1. CHEMICALS
natural: in foods
man-made/man-increased: nitrogen mustard, benzopyrene
2. UV RADIATION
3. IONIZING RADIATION
natural: radon gas, cosmic rays
man-made: x-rays, nuclear tests
57
(DNA Damage) UV radiation creates...? How?
pyrimidine dimers
by photon hitting bases
58
What is a pyrimidine dimer?
cross-links adjacent bases on SAME strand
59
What is the fate of DNA damage? (HINT: 3)
1. may be repaired
2. may kill the cell or cause the cell to kill itself
3. may become "FIXED" (becomes a permanent mutation)
60
How do DNA strand cross-links (ON THE SAME STRAND) kill cells?
block replication and replication and transcription
pyrimidine dimer is unrecognizable to polymerase (DNA and RNA) so polymerase stalls or falls off
61
What does it mean for DNA damaged to be "fixed"?
DNA damage becomes a permanent mutation
62
How do DNA strand cross-links (BETWEEN STRANDS) kill cells?
block replication and replication and transcription
inter-strand crosslink physically blocks polymerase from unwinding DNA
63
What are the two EXAMPLE damaged base mispairs?
O6-ethyl-guanine pairs with thymine
deaminated cytosine pairs with adenine
64
What are examples of mutation fixation?
1. replication of unrepaired misincorporation
2. replication of an unrepaired cytosine deamination
--> deminated cytosine = U
--> deaminated 5-Me-cytosine = T
65
If the cell containing damanged bases (e.g. deaminated cytosine or 5-Me-cysotine) then replicates its DNA before the deamination is repaired, then the mutation becomes ______. This results in...?
FIXED
one daughter cell with the fixed mutation and the other daughter cell with no mutation
66
What are examples of repair mechanisms?
1. polymerase proofreading
2. DNA mismatch repair
3. Uracil DNA glycosylase
4. Thymine DNA glycosylase
5. nucleotide excision repair
67
What is uracil DNA glycosylase?
enzyme that removes U from DNA
*resulting abasic site is filled in by polymerase
IF U IS NOT REMOVED, it will pair with A
****causing C/G --> T/A transition
68
What is thymine-DNA glycosylase?
enzyme that removes thymine from T/G mismatches
*resulting abasic site is filled in by polymerase
IF T IS NOT REMOVED, it will pari with A
****causing C/G --> T/A transition
69
What is nucleotide excision repair?
carried out by mutl-protein complex
removes bulky adducts from DNA (e.g. pyrimidine dimers caused by UV, benzopyrene-DNA adducts) ; also excised nearby nucleotides
**resulting single-strand gap is filled in by polymerase
70
What are the steps to nucleotide excision repair?
1. damage recognition
2. dual incisions
3. excision
4. gap-filling (by polymerase)
71
Xeroderma Pigmentosum
autosomal recessive, very rare
DEFECT OF NUCLEOTIDE EXCISION REPAIR
72
Lynch Syndrome
autosomal dominant, multigenic
DEFECT IN MISMATCH PAIR
73
About ____ new mutation becomes _____ every time a human cell divides
1, fixed
74
~___ mutation per genome per human cell division
1
75
Although the mutation rate per cell division is low, these mutation will ________ over the course of many _____ _________.
accumulate, cell divisions
76
What is the mutation rate per human generation?
~70 new mutations in each kid:
--> 60 point mutations
--> 10 other types of mutation (e.g. insertions, deletions, transposable element insertions)
77
Most mutations don't have the potential to effect _______. Why?
phenotype
coding sequences, promoter sequences, etc. are MUCH less abundant than introns, spacers, heterochromatin, etc.
****most random mutations will probably be in the unexpressed regions
78
What mutations DO have the potential to affect phenotype?
1. missense/nonsense mutations in protein-coding sequences
2. mutations that alter splice sites
3. mutations that alter binding sites for transcription factors in the promoter
79
Roughly __ _____ _____ mutation in each new kid. This new allele is probably _______.
1 new gene (not present in either parent)
**gene mutation: meaning changing gene function and phenotype
recessive
80
autosomal traits are caused by genes on
autosomes (chromosomes 1-22)
81
sex linked traiats are caused by genes on the
sex chromosomes (X orY)
82
Females have what two sex chromosomes
XX
83
Males have what sex chromosomes
XY chromosomes
84
what is special about the Y Chromosome
key genes that initiate the male developmental program
85
if someone doesnt have an Y chromosome they are
a female
86
Are the X and Y chromosome similar?
non-identical but share a small number of genes
87
when do the X and Y chromosomes pair and segregate (sperm)
meiosis 1
88
how many base pairs are on the X chromosome
there are 160 million base bairs
89
how many base pairs are on the Y chromosome
70 million bairs pairs
90
Y specific genes are involved in
male sexual differentiation
91
Most x sepecific genes encode
functions essential to both males and females
92
what is the male to female ration
1:1
93
where does a male get his X chromosome from and who do they transmit it too
A male gets his X chromosomes from his mother and transmits it only to one of his daughters
94
men are more frequantly affected by diseases caused...
by recessive alleles of X linked genes
95
Normal X chromosome contains
wild type allele of the X linked gene of interesta
96
affected X chromosome
contains recessive allele of the X linked gene of interest
97
X linked gene =
a genes that is on the X chromosome
98
X linked disease =
a genetic disease that results from inheriting disease-causing alleles of an X-linked gene
99
female carrier mates with normal male
*half her daughters will be carriers
*half her sons will be affected
100
affected male mated with normal female
* all his daughter will be carries
* none of his sons will be affected
101
Hemophilia A symptoms
excessive bleeding (including internally) and easy bruising
102
Hemophilia A is what type of disease
X-linked recessive pattern of inheritance
103
Hemophilia A is caused by what mutation
cause by mutation in the gene encoding Factor V111 which is required for blood clotting
104
treatment history of Hemophilia A (idk if we need to know this )
Up until mid 1960’s: No treatment (often
fatal by age 20)
* Mid 60’s: Factor VIII purified from donor
plasma (and injected into hemophiliacs)
* 1978-1985: Half of hemophiliacs treated
with donor plasma get HIV
* 1984: Factor VIII gene cloned by
Genentech
* 1994: Recombinant factor VIII available
105
what are some examples of Some X-linked recessive human diseases/traits
- hemophilia A
- hemophilia B
- Duchenne musculat dystrophy
-Retinitis pigmentosum
- Lesch Nyhan Syndrome
- Red-green color blindness
106
4 important featured of X-linked recessive Inheritance
1) typically many more males than females have the trait due to hemizygosity
2) a recessive male mated to a homozygous dominant female produces all offspring with the dominant phenotype and all female offspring are carriers
3) Mating of recessive males with carrier females give half dominant and half recessive offspring of both sexes
4) mating of homosygous recessive females with dominant males oriduce all dominant (carrier) female offspring and all recessive male offspring
107
4 Features of X-linked Dominant Inheritance
1) the dominant phenotype is equally frequent in males and females. That is about equal numbers of males and females show the trait
2) Homozygous and heterozygous females are affected, as well as hemizygous males
3) Heterozygous females mated to wild type males transmit the dominant allele to hald their progeny of each sex
4) Dominant hemizygous males mated to homozygous recessive females transmit the dominant trait to all their daughters, but none of their sons
108
In Dominant inheritance the dominant trait is typically found in
every generation
109
In dominant inheritance the affected kid is never born to
unaffected parents
110
In DOminant inheritance two affected parents can have a
unaffected kid
111
In X-linked dominant inheritance the gene in question is found where
on the X-chromosome
112
in an X-linked dominant inheritance what genotype do affected males and females have
affected males: XDY
affected females: XD XD or XD Xd
113
affected males in X- linked dominant inheritance will pass on the disease to
all of their daughters and none of their sons
114
Recessive INheritance is typically not see in
every generation
115
In recesisve inheritance affected kids can be born to
unaffected parents
116
X-linked recessive inheritance affected males and females have what genotype
affected males are Xd Y
affected females: Xd Xd
117
who is most affected in X-linked recessive linkage
males are affected much more often than females
118
what is penetrance
the probability that a genotype will manifest as a phenotype
119
100% penetrance means
that is you have the genotype you will show the phenotype
120
Less than 100% penetrance =
if you have the genotype you might not show the phenotype
121
Polydactyly is an example of
a dominant traits that has partially penetrant pedigree
122
what can make it hard or even impossible to distinguish a dominant inheritance from recessive inheritance
when there is partial penetrance
123
what is a new mutation
a genetic alteration that is present for the first time in a new child
124
what is are synonyms of new mutations
novo mutation or germline mutation
125
what can be ruled out if unaffected parents have an affected kid
dominance both autosomal and x-linked
126
what can be ruled out if two affected parents have an unaffected kid
recessivness both autosomal and x-linked
127
If an unaffected woman has an affected son or an affected man has an unaffected daughter what can be rulled out
X-linked dominance
128
if an affected women has unaffected son or unaffected man has affecteed daughter what can be ruled out
x-linked recessive can be ruled out
129
if unaffected parents have an affected daughter
it must be
autosomal recessive inheritance
130
if affected parents have unaffected daughter
it must be autosomal dominant
131
if the problem tells you the disease is rare then
you can assume that multiple carriers do not marry into the family, you can assume that the founder is a heterozygote
132
mitochondria have their own...
DNA genome which contains 37 genes
133
a zygotes mitochondria comes from the
mom's egg, not from the dad's sperm
134
Mitochondrial Inheritance is usually...
partially penetrant
135
Huntington's disease symptoms
- slowly progressive brain disease that causes changes in movement, thinking, and behavior
- neuronal degeneration
-dealth
136
Huntington's disease is which type of inheritance and penetrance
Rare autosomal dominante- complete penetrance
137
Huntington;s disease has what type of onset
Late onset -> 35-50 years of age
138
Huntington;s disease is an example of what type of mutation
gain of function mutation
139
wild-type protein function is
normal
140
null or amorphic protein function
dead--> zero
141
hypomorphic protein function
weak, less, leaky diminished, reduced but not zero
142
what are the loss of function types of mutations
null or amorphic, and hypomorphic
143
what is hypermorphic mutation protein function
increased, more than there should be
144
neomorphic mutation protein function
New, novel, something completely different from what the wild type protein does
145
what are the gain of function mutations types
hypermorphic and neomorphic
146
loss of function alleles are usually ...
recessive but not always
147
when the genotype --> normal pheontype of a LOF, we say that the locus id
haplo-sufficient (half is enough)
148
when the genotype of LOF has disease phenotype we say that the locus is
haplo- insufficient (half if not enough)
149
what type of allele is haplo-insufficeient
when a LOF allele is dominant
150
Gain of function alleles are usually
dominant
151
huntingtons disease is what type of protein mutation type
Gain of function --> neomorphic
152
incomplete dominance
heterozygotes have a phenotype intermediate to the two alleles
153
co-dominance:
the phenotype of both alleles is fully expresses in heterozygotes
154
multiple alleles
more than two alleles affect a phenotype
155
penetrance and expressivity
a mutation does not affect every individual or may cause phenotypes that differ in severity
156
pleiotropy:
one gene affects greater than one phenotypic character
157
environmental impacts:
genetically identical individuals show differnet phenotypes as a result of environmental factors
158
epistasis
a gene at one locus alters the phenotypic expression of a gene at a second locus
159
example of incomplete dominance in humans
hypercholesterolemia--> where HH has the best ability to make LDL recptors, Hh has mild ability to make LDL recpetors and hh has inability to make LDL receptors
160
allelic series
there is an order of dominance when multiple alleles are present
161
lethal alleles
sometimes the homozygous recessive genotype is embronic lethal
162
expressivity
the same mutant allele produces different phenotypes in different individuals
163
____ of all cancers are diagnosed at age 55 and older.
3/4
164
If you get cancer, a 5-year survival rate is ___%.
66%
165
Cancer is a ______ of ________ __________.
loss of growth regulation
166
Cells grow WHEN they shouldn't, forming a _______.
tumor
167
Cells grow WHERE they shouldn't --> _________, _________
invasion, metastasis
168
Cancer is a _________ __________ of __________ cells.
genetic disease of somatic cells
169
Mutations in specific genes can cause a normal cell to become _________.
cancerous
170
Somatic mutations occur _________ and are normally _________.
frequently, inconsequential
171
What are some of the genes that lead to cancer when mutated?
oncogenes and tumor suppressor genes
172
What is the comparison for oncogenes? What is the comparison when there is a mutation in this gene?
gas pedal for cell proliferation
mutation --> gas pedal stuck down
173
What is the comparison for tumor suppressor genes? What is the comparison when there is a mutation in this gene?
brakes for cell division
mutation --> brakes don't work
174
Mutations in ________ _________ _______ are required for a normal cell to become cancerous.
several distinct genes
175
The progressive _________ of ___________ explains why cancer occurs mainly in older adults.
accumulation, mutations
176
What types of mutations cause cancer?
spontaneous and induced mutations
177
Cancer is often the result of ___________ _____________.
spontaneous mutations
178
What are two INDUCED mutations that can lead to cancer?
UV radiation: caused from excessive sunbathing --> skin cancer (pyrimidine dimers)
benzopyrene: caused from cig smoking --> lung cancer (benzopyrene covalently bonds to G)
179
Cancer cells are typically ________ with many chromosome abberations.
ANEUPLOID
180
Many cancers are genetically ________, particularly at the __________ ______.
unstable
chromosomal level
181
Some chromosome rearrangements are ________ ________ to occur in specific types of cancer. Provide an example.
repeatedly found
ex: Philadelphia chromosome
--> translocation occurs in chronic myelogenous leukemia; causes over-expression of the ABL gene
182
What is carcinogenesis/tumorigenesis?
creation of cell capable of forming a tumor from a normal cell
183
What is tumor progression?
the progressive "evolution" of a tumor from a more benign to a more malignant state
184
What are the stages of tumor progression?
Stage 1: BENIGN (NOT CANCER)
--> 1 gene mutated
--> tumor cells grow only locally and cannot spread by invasion or metastasis
Stage 2, 3, 4: MALIGNANT (CANCER)
2: 2 genes mutated
3: 3 genes mutated
4: 4 genes mutated
--> invades neighboring tissues, enter blood vessels, and metastasize to different sites
185
benign tumor cells
NOT CANCER
grows only locally and cannot spread by invasion or metastasis
186
malignant tumor cells
CANCER
invades neighboring tissues, enter blood vessels, and metastasize to different sites
187
We are all ______ _________. Why?
genetically defective
*70 new mutations per child
*1 new gene mutation per child
*PLUS mutations that were inherited from parents
188
Who coined the term eugenics?
Francis Galton
189
What is eugneics?
idea that society should promote the marriage of the "fittest" people by providing $ incentives
190
What did the US eugenics movement focus on?
preventing "unfit" people from having children by forced sterilization
191
Buck v Bell
allowed forced sterilizations to continue
192
Over 60,000 _________ ___________ were performed on mostly _______ (and often _________-__________) people confined to _________ ___________.
forced sterilizations
African-American
mental hospitals
193
Despite being discredited after WWII, _________ __________ of marginalized groups continued to persist up until the _______'s in the US.
forced sterilizations
1970s
194
Define euploid.
cell that contains a WHOLE NUMBER multiple of the haploid set of chromosomes
195
Genes alone are not responsible for all ___-
variation seen between organisms
196
Human somatic calls (2n) and human gametes (1n) are both ______.
euploid
197
PKU (phenylketonuria)
autosomal recessive --> very rare caused by the absence of an enzyme involved in phenylaline breakdown
198
Aneuploid calls contain _______ or ___________ ______________.
missing or additional chromosomes
199
What are common types of aneuploidy?
monosomy: only 1 copy of a given chromosome in an otherwise diploid cll
trisomy: 3 copies
200
The most frequent cause of aneuploidy is __________ ____________.
chromosomal nondisjuction
201
What is polyploidy?
euploid but > 2n
202
Triploid plants are often ______.
infertile
203
epistasis requires
two or more different gene loci that control the same trait
204
when does epistasis occur
when there is phenotypic interaction between these two different genes
205
for epistatic genes, a dihybrid cross produces a
modified 9:3:3:1 ration of phenotypes
206
complementation analysis
a screen to find many mutants with phenotypes related to that process
207
what questions can be answered by complementation testing
do these organisms have mutations in the same or in different genes?
How many genes are responsible for the phenotypes observed?
208
two pure breeding strains with similar mutant phenotypes are mated --> if complementation occurs then
wild type offspring are obtaines --> the mutations affect two different genes
209
Two pure-breeding strains with similar mutant phenotypes are
mated if mutations fail to complement
the offspring have the
mutant phenotype à the mutations affect the same gene
210
In humans, ______ is lethal before or shortly after birth.
polyploidy
211
Each gamete contains how many total chromosomes?
23
212
Describe the process of meiosis.
1. meiosis I: starts with 2 sets of chromosomes (one from each parent)
2. disjunction I: divides into 2 (each cell has 2 sets of chromosomes)
3. meiosis II/disjunction II: both cells divide again (each cell has one set of chromosomes)
213
What happens in a meiosis I non-disjunction? What are the gamete results?
set of chromosomes do not separate in meiosis I (e.g. X + Y do not separate)
RESULTS: (sex) XY, XY, 0, 0
214
What happens in a meiosis II non-disjunction? What are the gamete results?
ONE set of chromosomes do not separate in meiosis II (e.g. set of X chromosomes don't separate)
RESULTS: (sex) XX, 0, Y, Y
215
If there was a non-disjunction in meiosis II with the Y set of chromosomes during sperm production and these perm fertilize a euploid egg, what would the resulting zygotes be?
X gametes: normal
--> euploid female (46, XX)
0: aneuploid female (45, X)
YY: aneuploid male (47, XYY)
216
What is a nondisjunction?
chromosomes or chromatids that fail to "disjoin" during meiosis
217
Nondisjunction in meiosis I produces gametes with a ______ of _________ _________.
pair of homologous chromosomes (e.g. XY)
218
Nondisjunction in meiosis II produces gametes with a ______ of __________ _________.
pair of sister chromatids (e.g. XX or YY)
219
Fertilization with a gamete that experienced a non-disjunction produces a zygote with a _________ or a __________.
monsomy or trisomy
220
The risk of nondisjunction ________ dramatically with maternal age.
increases
221
trisomy-X
47, XXX (female)
0.1% (1 per 1000 female births)
222
double-Y
47, XYY (male)
0.1% (1 per 1000 male births)
223
Klinefelter Syndrome
47, XXY (male, sterile)
1 per 1000 male births
224
Turner Syndrome
45, X (female, sterile)
1 per 2000 female births
225
An extra or missing X or Y chromosome as a relatively _____ effect in comparison to an extra or missing ______.
mild, autosome
226
About _____ of human pregnancies are lost spontaneously after implantation. What's the lead known cause of this?
1/3
chromosome abnormalities are the leading known cause
227
A minimum of ____-____% of conceptions have a chromosomal abnormality.
About approximately what percent of these conceptions spontaneously abort because the fetus died?
10-15%
at least 95%
228
Trisomy 21
most common autosomal aneuploidy
--> leads to down syndrome
--> approx. 75% of trisomy 21 conceptions are spontaneously aborted
229
Trisomy 13
patau syndrome
230
Trisomy 18
edward syndrome
231
All other trisomies and monosomies are ___________ _______.
embryonic lethals
232
What is translocation?
interchange of genetic info between non-homologous chromosomes
233
Translocation is a result from a mistake by the ___________ __________.
recombination machinery
234
What is inversion?
genetic rearrangement in which the order of genes is reversed in a chromosome segment
235
Both translocation and inversion are __________ _________. They do not result in a _____ or ______ of much chromosomal material.
balanced rearrangements
loss or gain
236
What are chromosome deletions?
missing chromosome segment
237
Large deletions are often _______ (even in ______________).
LETHAL
even in heterozygotes
238
What are gene duplications?
chromosomes segment present in MULTIPLE copies
239
Gene duplications provides material for _______.
evolution
240
Tandem duplications are...? They are often a result from?
ADJACENT repeated segments
unequal crossing-over
241
Deletion and duplications are ____________ _________. They result in a ________ (__________) or __________ (___________) of a chunk of chromosome.
UNBALANCED rearrangements
loss (deletion) or gain (duplication)
242
Deletions are often ______ _______ than duplications.
MORE SEVERE
243
What is recombination?
the process responsible for crossing-over in meiosis
also used in some forms of DNA repair
244
Recombination mistakes can lead to _________ ________.
chromosome rearragement
245
When there is a recombination mistake between similar sequences on NON-HOMOLOGOUS chromosomes, it is?
translocation
246
When there is a recombination mistake between similar sequences within a chromosome, it is?
inversion or deletion
247
When there is a recombination mistake between tandemly repeated sequences on HOMOLOGOUS chromosomes, it is?
duplication or deletion
248
What are the phenotypic effects of the multiple genetic steps required for a normal somatic cell to become a malignant tumor? (TLDR: HALLMARKS OF CANCER) (HINT: 11)
1. self-sufficiency in growth signals
2. insensitivity to anti-growth signals
3. tissue invasion and metastasis
4. limitless replicative potential
5. sustained angiogenesis
6. evading apoptosis
7. avoiding immune destruction
8. tumor-promoting inflammation
9. genome instability + mutation
10. deregulating cellular energetics
11. tumor cells can evolve resistance to chemotherapy drugs
***each of these phenotypic steps requires at least ONE genetic "step"/mtuation
249
Explain "self-sufficiency in growth signal."
CANCER CELL GROWS OUT OF CONTROL IN AN UNREGULATED FASHION (doesn't wait for permission signals from other cells)
***requirement to become successful cancer
250
Cell division (growth) is normally a ________ ___________ _________.
highly regulated process
251
Stem cells receive permission from other cells to divide. This permission comes in the form of _________ __________ released by _________ _________.
growth factors released by other cells
252
Many components of growth control are ___________________.
proto-oncogenes
253
Mutations can turn _______________ into _______________ (cancer-causing genes).
proto-oncogenes into oncogenes
254
Describe the steps of the normal growth-control pathway.
1. growth factor attaches to receptor on cell
2. signaling enzymes dispatched to cell nucleus
3. signal reaches nucleus, activates transcription factors
4. activates cell proliferation
255
Oncogenes activate ______ ________.
cell proliferation
256
Mutated alleles (_________) tell the cells to grow and divide all the time, even when there's ____ _______________ ____________.
oncogene
no permission signal
257
When mutated, oncogenes contribute to _______. Their normal, wild-type function is? This wild-type allele is called?
cancer
normal, wild-type function is to regulate cell division
wild-type allele name: proto-oncogenes
258
Cancer-causing mutations are (dominant/recessive).
DOMINANT
259
What are FOUR possible oncogene-creating mutation?
1. cell makes its own growth factor
2. receptor "thinks" it's bound to GF when it's not
3. signaling enzymes think they are receiving "go" signal from GF
4. transcription factors are OVEREXPRESSED; turn on their target genes regardless of upstream regulation
260
Explain "insensitivity to anti-growth signal."
loss of both wild type alleles of one or more tumor suppressor genes
***requirement to become successful cancer
261
Tumor suppressor genes are _____________ of ____________ _________.
guardian of genome integrity
262
If there is a mutation in the tumor suppressor genes, what happens?
MUTATIONS/REARRANGEMENTS ACCUMULATE
263
Cancer-causing mutations in tumor suppressor genes are typically (dominant/recessive).
RECESSIVE
264
If there is a mutation in the tumor suppressor genes, what happens to the GENE PRODUCT aka protein?
gene product isn't made or doesn't function at all
--> loss-of-function/null alleles
265
Cancers ___________ to new regions in the body.
metastasize
266
What is metastasis?
process in which tumor spreads to a distant organ or tissue
267
___% of cancer deaths are due to cancers spreading throughout the body.
>90%
268
Cancer is ____ _______ disease, but _____.
not one, many
269
In different tissues, ___________ ________ must be mutated in order for a cell to become cancerous.
different genes
270
What gene is mutated in approx. 50% of human tumors?
p53
271
272
What signaling pathway is mutated in many different types of tumors?
RAS/MAPK pathway
273
True or False: A predisposition to some types of cancer can also be inherited.
TRUE
274
About ___-___% of all cancers are attributable to the inheritance of an allele that resulted in greatly increased cancer risk.
5-10%
275
Inherited cancer syndromes are typically _________ _________.
autosomal dominant
276
For inherited cancer syndromes, each of an affected person's cells now contains...?
one of the steps in a multistep cancer pathway
277
For inherited cancer syndromes, the other mutations required for tumorigenesis and tumor progression still occur _______.
somatically
278
In smokers who get lung cancer most of the mutations are ________, but _______________ mutations still play a role.
induced, spontaneous
279
Cancer is a _________ disease of _________ cells.
genetic, somatic
280
A key characteristic of cancer is the...?
loss of growth control
281
(One/Multipple) mutation(s) is/are required for cancer to develop. Most of these mutations are __________/________?
MULTIPLE
spontaneous/random
282
Oncogenes (mutated) are usually...
GAIN OF FUNCTION
283
Mutated tumor suppressor genes are usually...
LOSS OF FUNCTION
284
(T/F) Cancer is a single disease.
FALSE
285
(T/F) Cancer is many different diseases.
TRUE
286
(T/F) Genetics are involved for inherited cancer predisposition syndromes.
TRUE
