Genetics SSN Flashcards
(248 cards)
1
Q
CHEK2, BRCA1/2
A
breast cancer mutations
2
Q
AD predisposition to arrhythmia
A
Long Qt syndrome
3
Q
KCNQ1, KCNH2
A
treat with beta blockers
4
Q
KCNH2
A
avoid hypokalemia
5
Q
SCN5A
A
mexilitine and pacing to stop bradycardia
6
Q
aggravated by exercise, adrenaline
A
Long QT 1
7
Q
aggravated by sudden unexpected sound
A
Long QT 2 and 3
8
Q
AD, repsonse to certain meds (anesthesia)
A
malignant hyperthermia
9
Q
extra or missing chromosomes, most common reason for spontaneous abortion
A
aneuploidy
10
Q
Trisomy 16 is ____ common than trisomy 21/22
A
more
11
Q
most aneuploidy happenis in
A
oogenesis
12
Q
Meiosis 1 errors are ____ common than meiosis 2 errors
A
much more common
13
Q
chromosomes condense, centromeres separate, interphase Mts break down, spindle Mts assemble
A
prophase
14
Q
nuclear envelope breaks down, Cr attach to spindle Mts and start to move
A
prometaphase
15
Q
Cr align at spindle equator, metaphase plate, bipolar spindle assembly complete
A
metaphase
16
Q
sister chromatids separate, spindle poles move apart
A
anaphase
17
Q
daughters arrive at poles and decondense, nuclear envelope reassembles, contractile ring assembles
A
telophase
18
Q
two new cells separate
A
cytokinesis
19
Q
when no meitosis is happening
A
interphase
20
Q
only in gonads, cells go from diploid to haploid
A
meiosis
21
Q
males perform meiosis
A
life long
22
Q
females perform meiosis
A
14 weeks into gestation
23
Q
Meiosis 2 occurs in females
A
after gestation
24
Q
cells commit to meiosis
A
leptotene
25
homologous pairs line up
zygotene
26
crossing over occurs, at least once per Cr, via chiasmata for proper segregation
pachytene
27
homologous chromosomes repel each other
diplotene
28
greatest contraction of chromosomes
diakinesis
29
homologs separate in
meiosis one
30
sister chromatids separate in
meiosis two
31
abnormal disjunction occurs in which phases
Anaphase, metaphase
32
in meiosis 1, both chromosomes pulled into one daughter cell together, giving one trisomic embryo and one monosomic embryo
true nondisjunction
33
in meiosis 1, both chromosomes pulled into same daughter cell separately (failure to pair)
achiasmate nondisjunction
34
no synapsis, no recombination, independent segregation of homologs
in achiasmic nondisjuction
35
one full and one half chromosome pulled into daughter cell
premature separation of sister chromatids
36
primary error source in meiosis
premature separation of sister chromatids
37
crossing over not at hotspots ____ chances of aneuploidy
increases
38
sister chromatid cohesion is facilitated by
cohesin
39
release of cohesion complexes from chromatin at meta/anaphase is facilitated by
separase
40
inhibits separase until ubiquinated by anaphase
securin
41
advanced maternal age associated aneuploidy is caused by
defective cohesion complexes
42
when some cells have different # of chromosomes in same tissue
mosiacism
43
mosiacism is caused by
Post-zygotic (mitotic) chromosome malformation
44
CdK, activated by cyclin and dephosphorylation to phosphorylate other proteins
cell cycle control system
45
Cdk-inhibitor OR ceased production of control system parts
override control system, as in cancer
46
prevent Cdc20 from interacting with APC/C cyclosome
checkpoint proteins
47
APC/C cyclosome sends securing and cyclin B to proteasome to
free separase (separate sister chromatids)
48
different mutations within same gene result in similar phenotype with varied severity
allelic heterogeneity (as in CF)
49
delta F508
most common CF mutation
50
causes defective prossessing so CTFR protein gets stuck in cell
delta F508
51
mutations within gene at different loci cause same phenotype
locus heterogeneity
52
hyperphenylalaninemia
example of locus heterogeneity, phenotypic heterogeneity
53
classic from in mutated PAH, other varients in BH4 metabolizing enzymes
hyperphenylalaninemia
54
one gene involved, different mutations in same gene result in very different phenotypes
phenotypic heterogeneity
55
different mutations in PAH gene may cause
very different severity of phenotype
56
most mutations, point and truncations
loss of function
57
50% of normal levels results in abnormal phenotype
haploinsufficiency
58
haploinsufficeincy example, causes hyperglycemia after a meal
mature onset diabetes of youth
59
gene becomes superactive or aquires new function
gain of function mutation (huntingtons)
60
more polyglutamine repeats causing earlier onset of disease (worse as inherited)
anticipation (huntingtons)
61
rare in humans, e.g. tempature sensitive mutations in androgen receptor
conditional mutations
62
50% of normal levels is poison (actively does something detrimental)
dominant negative mutation, e.g. osteogenesis imperfecta
63
AD mutatio nin procollagen gene, form defective collagen fibrils causing poor mineralization of bone
osteogenesis imperfecta
64
enzyme deficiency inheritance is almost always
AR, since 50% is usually sufficient
65
treat phenylalaninemia with restricted diet, other BH4-requiring end-products such as
serotonin, L-dopa
66
humans have this many pairs of chromosomes
23
67
how many base pairs per set of chromosomes
three billion
68
how many genes
twenty thousand, many more gene products
69
how many bases
five
70
purines, have three H bonds
G, C
71
pyramidines, have 2 H bonds
C, U, T
72
RNA has ____ on 2' C, DNA has ____
hydroxy, H
73
5' end, near transcription start site
promoter
74
contain coding sequence
exons
75
silent mutations are possible because
DNA code is redundant
76
always ATG (methionine)
start codon
77
UAA, UAG, UGG in humans
stop codon
78
polyA signal (AATAAA)
generates polyA tail in mature RNA
79
5' cap added onto mature RNA
CAP site
80
GT
5' splice site
81
A
branch site
82
AG
3' splice site
83
Short non-mRNAs, loads RNA silencing complex (RISC), translational repression of mRNA or mRNA destruction
microRNA
84
pase pairs per histone
200
85
changes activity at different histones
methylation, acetylation
86
tightly packed, low transcriptional activity
heterochromatin
87
satellite DNA (tandem repeats clustered together) often found
heterochromatin
88
loose chromatin, high transcriptional activity
euchromatin
89
regulate genes nearby
Cis regulatory elements
90
can be far away, brought near by 3D folding
trans regulatory elements
91
may occur due to misalignement in mitosis, may lead to divergence of function e.g. globins
gene duplication
92
can move gene fragments around, e.g. hemophilia
transposable elements
93
transcript destroyed if stop codon inserted too early
Nonsense-mediated decay
94
disease prevalence
q squared
95
caculate carriers (heterozygotes)
2pq
96
point mutation example: from FGF receptor GOF mutation (g to A or C)
achondroplasia (also, cancer, due to defects in DNA proofreading or repair
97
repeat expansion examples
fragile X, huntington's
98
reduced penetrance causes
induced by age (Huntington's, colon cancer), sex-limited (male pattern baldness)
99
expressivity (severity) example
neurofibromatosis: cafe au lait spots
100
one genetic change, wide array of effects in multiple organ systems (e.g. Marfan's, eye bone and heart)
pleitropy
101
unfavorabley lyonization, homozygous, 45X or 46XY females
female shows phenotype in X-linked recessive conditions
102
maternal inheritance, many children, many organs (esp. brain, heart, muscle), phenotype depends on heteroplasmy
mitochondrial inheritance
103
mRNA detection, mRNA expression to deterine under or over expression of genes
Northern Blot, RNA by in situ hybridization
104
protein detection, e.g. dystrophin in Duchenne's muscular distrophy
Western Blot
105
detect protein via fluorescent Ab in tissue
immunocytochemistry
106
uses restriction enzymes to cut DNA and run on fluorescent gels to bind and visualize DNA fragments
southern blot
107
southern blot probe must be
1000 bps long, or allele-specific oligonucleotides
108
use for tandem repeats (huntingtons) large deletions, missense mutations
southern blot
109
don't use for missense mutation, deletion or transloacation may not be detected at restriction site or by probe
southern blot
110
???
use PCR
111
don't use for allele dropout of enzyme, large deletions on only one chromosome
PCR
112
can detect heterozygote deletion
quantitative PCR (multiple ligation primary annealing PCR)
113
use: single bp or other small deletion, missense mutation, etc
genome sequencing
114
don't use for tandem repeats, copy number variations
genome sequencing
115
don't use for detecting missense and most other mutations
multiple ligation primary annealing PCR
116
use for constitutional deletiona nd duplication for large scale mutations (chromosome imbalance) e.g. in cancers
comparative genomic hybridization
117
don't use for small mutations (current chip density is 3Mb)
comparative genomic hybridization
118
detect gene expression and visualize via Manhattan plots
Genome-wide association studies
119
can see heterozygote and homozygote missense mutations. Not used for mutations involving many base pairs
Genome-wide association studies
120
Safer (.5% chance of miscarriage), done at week 16-20
amniocentesis
121
Riskier (1%), but done at week 10-12
CVS
122
classic example of at-birth genetic screening
phenylketonuria (PKU)
123
true positives/(true positives + false negatives)
sensitivity
124
higher sensitivity means fewer
false negatives
125
true negatives/(true negatives + false positives)
specificity
126
higher specificity means fewer
false positives
127
changing gene expression patterns via DNA methylation and histone modification
epigenetics
128
disease phenotype in Turner's syndrome (XO) proves
some genes escape X activation
129
dominant mechanism of X inactivation, transcribed but not translated
Xist
130
areas of DNA that have high concentration of adjacent Cs and Gs
CpG islands
131
methylation silences genes ____, by recruiting proteins that modify chromatin to block Tfs
indirectly
132
propagates methylation pattern from parent cell to daughter cell
DNA methyltransferase
133
when bad Xs die faster than they are replaced, so good X dominates
phenotypic rescue
134
rescue example, where B cells only have good X activated
X-linked Agammaglobulinemia
135
accidental activation of more of good X than bad in target tissue explains
why rarely a woman may have XlD Duchene's muscular distrophy
136
XlD that effects only females, because males die in utero, causes rapid neuropsychiatric decline in childhood
Rett's syndrome
137
silencing the expression of just one allele on a gene, depends on sex of parent who gave it
imprinting
138
how does imprinting lead to disease?
it doesn't. Disruptions in imprinting lead to disease
139
materal imprint restricts growth, paternal imprinting speeds growth
Haig hypothesis
140
Are most fetal genes controlling growth imprinted?
Nonsense-mediated decay
141
disruption of imprinting due to loss or gain of methylation
epimutation
142
empty egg with double-dose of dad's imprinting genes
hydatidiform mole (tumor)
143
promotes fetal growth, paternally activated (methylated) DMR region does not allow silencing CTCF to bind
IGF2
144
caused by gain of function mutation that allows materal allele DMR region to be methylated
Beckwith-Weidmann Syndrome (giant baby with tumors)
145
dad's DMR region is not methylated; all IGF2 is restricted
Silver Russell Syndrome: severe interuterine growth restriction
146
phenotypes of imprinting lesoins involve abnormal growth or behavior, not
anatomical malformations
147
proportion of individuals carrying a gene variant who express a particular phenotype.
penetrance
148
proportion of variance in phenotype expression in a populatoin that can be accounted for by genetics
heritability
149
difference in concordance between monozugotic and dizygotic twins is attributed to
50% difference in genes
150
genetic loci coordination with disease varies greatly why?
overestimation of heritability, rare variants with large impact not picked up, genome duplication/deletion not measured well
151
polygenic disease example
obesity/type II diabetes, FTO and MC4R
152
in mice, leptin mutations and feeding in first five weeks of life
influenced resulting phenotype
153
inhibits appetite
leptin
154
in urea cycle disorders, excrete hippurate using
sodium benzoate (diversion)
155
in familial hypercholesterolemia, reduce bile saltes with ____ and inhibit HMG CoA reductase with ____
cholestyramine, statins (diversion)
156
in hemochromatosis, use ____ to deplete excess iron
phlebotomy (depletion)
157
In LDL recepter deficiency, use
plasmapheresis (depletion)
158
in PKU, cofactor to increase enzyme activity
cofactor BH4
159
in Gaucher, help mutant protein to fold correctly using
chaperone AT2101
160
in MPS 1,2,4; Gaucher, Fabry and Pompe, use
protein replacement therapy
161
treat hereditary agiodema (caused by mutation in esterase inhibitor)
danazol to increase expression
162
treat sickle cell/thalassemia with ____ to decrease methylation of fetal Hgb
butryate
163
treat dominant negatives with ____ to initiate degradation of mutant allele
RNAi
164
due to loss of cells in anterior horn of spinal cord, caused by mutations in Survival Motor Neuron genes SMN1/2
Spinal Muscular Distrophy (no effect on cognition)
165
When SMN1 lacks ____, it is unstable and rapidly degrades, leading to SMA
Exon 7
166
this is used to enhance normal splicing of SMN1/2
SR
167
use this to increase the expression of SMN2, lessening the phenotype severity
Sodium Phenylbutyrate
168
treat nonsense mutations in CF and Duchenne MD with ____ that read through stop codons
aminoglycosides
169
corrects delta508 mutations, allow mutant protein to not get stuck in RER, get to the cell surface
curcumin
170
convert duchenne MD to becker MD, a less severe form
modify splicing to restore normal reading frame.
171
transplantation treats
genetic diseases with single organ involvment
172
treat hemoglobinopathies, immunodeficiencies, storage disorders
bone marrow transplant
173
treat small amounts of cells in babies and kids
cord blood
174
many inborn errors of metabolism
liver transplant
175
treat fetus with cortisol to prevent virilizatoin of females and reduce shock due to low Na and high K
congenital adrenal hyperplasia, prenatal treatment
176
gene addition is performed with
vectors: naked DNA, adenoviruses, oncoretroviruses, lentiviruses
177
can correct single gene defects, can add new functions to cells, can increase immune response to cancer
gene addition
178
abnormal beta globin
sickle cell disease, can be treated with gene therapy
179
decreased or absent beta globin due to point mutations
beta thalassemia, can be treated with gene therapy
180
normal immune function in 9/10 children, 3/10 developed leukemia due to insertion near oncogene
SCID severe combined immunodeficiency
181
cerebral demyelination in children with enzyme deficiency, treated with lentivirus, no evidence of mutagenesis
adrenoleukodystrophy
182
early onset blindness, focused on RPE65, inserted directly into eye to avoid mutation
leber congential amaurosis: restored light and some gross vision
183
viral replication leads to infection, insertional mutagenesis, benign and malignant tumors, clonality
safety issues of gene therapy
184
federal law stating that insurers and employers cannot discriminate based on genetic information
GINA
185
Does GINA protect against discrimination in life insurance, disability insurance or long-term care?
No
186
Robbery with a deadly weapon not excsued by 47 XYY aneuploidy
Millard v. State of Maryland
187
successfully sued Arizona SU after blood samples donated for diabetes research were being used to research inbreeding and schizophrenia
Havasupai Tribe
188
In NY, can patients be genetically tested without giving consent?
No
189
doctors must
inform patients of risk, explain implications for family, offer services
190
genetic information must be shared with family?
no, it is confidential to the individual
191
hospital, doctor or testing company can be sued for ___ if a test is misread, leading to the birth of a baby that the parents would have wanted to abort
wrongful birth
192
encourages private companies to invest in genetic research
argument for gene patenting
193
lack of incentive to improve testing, high price, slow turn-around times, no means of independent conformation
argument against gene patenting
194
is preimplantation genetic diagnosis regulated?
no, is now used for controversial traits such as gender selection
195
Trisomy 21, 18, 13
Non-fatal autosomal aneuplodies
196
maternal meiosis 1 non-disjunction, hypotonia, low ears, simian crease, tow space, declined cognitive development, risk of leukemia and heart defects
Trisomy 21, Down syndrome
197
clenched fists, rocker bottom feet, small gestational aga, 90% heart defect, 10% 1 year survival
Trisomy 18, Edward Syndrome
198
95% abort, 75% due to meiotic nondisjuntion, 20% translocations, holoprosencephaly, cleft lip and palate, eye problems
Trisomy 13, Patau Syndrome
199
short, infertile, broad chest, webbed neck, 1:5000 female birth, 80% due to loss of pateral X
Monsomy X, Turner syndrome
200
sterile, small testes, low testosterone, gynecomastia, tall, 1o point lowered IQ, 1:1000 males
XXY, Klinefelter's syndrome
201
Klinefelter with triple X
possible sterility
202
Klinefelter with XYY
possible rediction in IQ, tall
203
maternal age correlates with all aneuploidies except
45X and XYY
204
chmsm 5p, chmsm 4p
deletion examples
205
mewing cry, microcephaly, mental retardation
chmsm 5p, Cri-du Chat
206
distinct face, 87% due to pateral de novo deletion
chmsm 4p, Wolf-Hirschhoron
207
mitogens (PHA)
stimulates mitosis
208
Colchicine
spindle poison, stops mitosis in metaphase
209
route for banding, trypsin and giemsa
G banding
210
R banding
G banding reversed
211
centromeres and heterochromatin
C banding
212
first method, quinacrine
Q banding
213
short arm is called
p
214
long arm is called
q
215
size: acro is ___ than sub-meta is ___ than metacentric
smaller than
216
Chmsm 1, 9,16, Y
large heterochromatic regions
217
Chmsm 13, 14, 15, 21, 22 (also Y)
acrocentric
218
how many proteins in the proteosome?
80-100000
219
What's worse, monosomy or trisomy?
monosomy
220
have no gain or loss of genetic material
balanced translocations
221
results in partial monosomy and partial trisomy
unbalanced translocations
222
translocation of acrocentric chmsm, fusion at centromeres, and loss of short arm fusion
robertsonian translocation, carriers have 45 chmsm
223
two breaks in one chmssm
inversion
224
pericentric v. paracentric inversion
peri inludes the centrosome
225
crossover leads to duplication/deletion of distal DNA
pericentric inversion
226
crossover leads to acentric fragment and dicentric chmsm (both lethal to offspring)
paracentric inversion
227
small centromere containing fragments from trisomy rescue
marker chmsm
228
misegregations lead to duplications of shirt or long arm (and absence of counterpart) in daughter cell
isochromosomes
229
Hybridzing DNA probes to pateints chromosomes: good for microdeletoins (~1Mb loss)
FISH: fluorescent in situ hybridization
230
paternal deletion of 15q11.2, floppy at birth, hungry, underweight, small genitalia
Prader-Willi
231
Maternal deletion of 15q11.2 innappropriately happy, speech delay, excitable
Angelman
232
microdeletion of 22q11.2
DeGeorge
233
FISH has subtelomere probes b/c
telomeres have highest concentration of genes, thus biggest impact of deletions
234
FISH for CVS or amniocentesis
interphase fish, results in 1-2 days, v. 7-10 for conventional cytogenetics
235
advanced maternal age, abnormal maternal serum (risk for trisomy 18 or 21), risk of neural tube defects, prenatal ultrasound abnormalities
use Interphase FISH
236
limits of interphase FISH
reduced sensitivity, or recognizes most frequent abnormalities
237
preimplantation genetic diagnosis is done with
polar bodies from oocytes, blastomeres from embryos
238
what guides choice of FISH probes?
clinical phenotype
239
scrape marker off of chromosome, use it to make probe
reverse FISH, very expensive
240
spectral karyotyping
multicolored FISH
241
stain normal chromosome with DAPI, label control and experiment
comparative genomic hybridization (CGH)
242
only detectsimbalances greater than 3-10 Mb, depends on banding resolution which varies between preparations
CGH limitations
243
like CGH but w/representative DNA sequences (not whole chromosomes) affixed to plate
microarrays
244
small gains or deletions not seen with large probes, probes may skip site of gain/deletion,
microarray limitations
245
detects greater than 100-200kb changes
BAC platform (microarray)
246
detects greater than 1-100kb changes
oligonucleotide platform (microarray)
247
single neucleotide polymorphism olionucleotide microarray analysis
SOMA
248
benign variation, aneuploidy, partial aneuploidy, microdeletions and duplications far below traditional thresholds, long stretchs of homozygosity,
SOMA
