Clinical Genetics Flashcards
(167 cards)
1
Q
A
B
2
Q
A
C
3
Q
A
C
4
Q
A
B, C
5
Q
A
B
6
Q
A
B
(or 13)
7
Q
A
A, C, D
B is wrong – its 150-300 bp
8
Q
A
A, D
B is wrong – it is for TARGETED testing (but still not sure, can be right?)
C is wrong – for C you should use Sanger sequencing, not NGS
9
Q
A
C
10
Q
A
E
11
Q
A
B
A thiopurine drug like thioguanine used in treating acute leukemias and some inflammatory diseases
Its efficacy and toxicity are heavily influenced by pharmacogenetics, i.e., how your genes affect drug metabolism.
HGPRT = activates thioguanine
TPMT = inacticates thioguanine by methylation
XO = oxidizes thiopurines to inactive metabolites
12
Q
A
C
13
Q
A
C, D
A is NORMAL
B is INTERMEDIATE (along with 1*3)
14
Q
A
C
15
Q
A
A, B, D
16
Q
A
C
AIS is genetic condition where a person who is genetically male (46,XY) is partially or completely resistant to androgens
- Mutation in the androgen receptor (AR) gene, located on the X chromosome
- Inherited in an X-linked recessive pattern
17
Q
A
C
(GI is 2nd most common)
18
Q
A
A, C, D
B is wrong = on average there is >120 polymorphisms in an average human gene
19
Q
A
B, C, D
A is wrong = null mutation results in NO signal
Hypomorph = LoF mutation where gene product retains partial activity but less than normal
Non-interacting hypomorph = when it has reduced function and CANNOT bind to normal binding partners
20
Q
A
D
A balanced translocation involves the exchange of genetic material between two chromosomes without any net gain or loss of genetic content. This usually doesn’t affect the carrier directly, but it can have consequences during reproduction
✅ Possible consequences of a balanced translocation:
Balanced offspring → possible if the child inherits the balanced arrangement.
Habitual miscarriages → due to unbalanced gametes leading to chromosomal abnormalities in embryos.
Infertility → due to problems in gamete formation (meiotic pairing issues).
❌ Inversion:
An inversion is a different kind of chromosomal rearrangement where a segment of a chromosome is reversed end to end — not a translocation.
21
Q
A
A
It is considered a founder mutation, particularly in northern European populations = a genetic change that originated in a single individual (the “founder”) and was passed down to many descendants in a population.
The p.C282Y mutation is very uncommon in African, Asian, and Southern European populations
It causes a single amino acid change — cysteine (C) to tyrosine (Y) at position 282 → missense mutation.
NOT highly penetrance = Although common, the mutation shows low clinical penetrance – many homozygous individuals never develop clinical symptoms of iron overload.
22
Q
A
A
23
Q
A
B, D
24
Q
A
B, D
A is wrong: 5-10%
25
A, C, D
26
A, B, D
A is wrong = more common in Caucasians
C is wrong = made of 12 transmembrane domains
D is wrong = it's the 508
27
A, B
CF screening in newborns using IRT = immunoreactive trypsinogen
Newborn screening is mandatory in most European countries, and ALL US states
28
B, C
A is wrong: Familial anticipation is when a genetic disorder appears earlier in life + with increased severity in each successive generation. It is typical in MONOGENIC disorders e.g. Huntington's myotonic dystrophy, fragile X syndrome -- These disorders are caused by trinucleotide repeat expansions, which get longer with each generation — leading to earlier and more severe symptoms.
D is wrong: FISH is for large scale testing
29
C
30
B
❌ "There is a known predictable pattern of recognition or suspected underlying etiology in case of association"
Incorrect. By definition, an association is a non-random occurrence of anomalies that tend to appear together, but without a known unifying cause or mechanism.
A syndrome or sequence has a clearer etiology or mechanism — associations do not.
✅ "A syndrome can be mitochondrial"
Correct. Mitochondrial diseases can cause syndromes, such as MELAS, MERRF, and Leigh syndrome, all due to mitochondrial dysfunction.
❌ "Extended fingers are typical in POTTER sequence"
Incorrect. Potter sequence is due to oligohydramnios (low amniotic fluid) → causes limb contractures, flattened face, and pulmonary hypoplasia. Contractures, not extended fingers, are typical.
❌ "In deformation, normal growth is halted prematurely"
Incorrect. Deformation refers to mechanical forces altering the shape of a normally developing structure, not halted growth. Premature halting of growth fits better with dysplasia or disruption
31
B, C
32
A, C, D
Not all genes have introns e.g. histone genes, those in the mitochondria
33
C
34
E
35
C
If isolated -- 12/100
36
D
37
C
Aneuploidy is a condition in which a cell or organism has an abnormal number of chromosomes — not a multiple of the haploid number (n)
Patau = 13
Edwards = 18
Down = 21
DiGeorge syndrome is caused by a microdeletion on chromosome 22 = euploidy!
38
A
39
B, C
Expanded Carrier Screening (ECS) is a genetic test offered to individuals or couples to determine whether they carry mutations in genes associated with a wide range of inherited genetic disorders, regardless of ethnicity or family history.
Who Should Consider ECS?
Individuals or couples planning a pregnancy or already pregnant
People with no known family history (it can still uncover silent carrier status)
Those from any ethnic background (many conditions are not limited to one group)
40
A
41
E
42
B
43
A
44
D
Achondroplasia is the most common form of dwarfism, caused by a genetic mutation affecting bone growth, particularly in the long bones.
= single point mutation
= autosomal dominant -- 80% are de novo mutations in average-height parents
45
A
Angelman syndrome = loss of function mutation, mostly due to maternal deletion of 15q11.2-q13
Clinical Features:
Severe developmental delay and intellectual disability
Absent or minimal speech
Ataxia (uncoordinated movements) and tremors
Seizures, often starting in early childhood
Happy personality: frequent laughter, smiling, and hand-flapping
Small head / microcephaly
Sleep disturbances
Fascination with water
46
A, C
47
C
48
C
49
C
50
1. Cystic fibrosis -- (D: autosomal recessive)
2. Osteogenesis imperfecta -- (B: autosomal dominant)
3. Rett syndrome -- (C: X-linked dominant)
4. Hemophilia A -- (A: X-linked recessive)
51
A, B, D
52
A, C, E
53
C
54
Autosomal dominant
Parents affected?: if yes, DOMINANT, if no: RECESSIVE
DOMINANT: if male-male transmission = AUTOSOMAL, if not = X-LINKED
RECESSIVE: if males only affected: X-LINKED, if male or female = AUTOSOMAL
(opposite of each other)
55
A
56
B
(1/98)
The older you are, the higher the risk
The later you are in the pregnancy, the less the risk
57
A, D
Bayesian analysis is a statistical method that involves updating the probability of a hypothesis as new evidence or data becomes available
= most commonly used in genetic risk assessment
58
A if mom is a carrier
but also 0% (D) if mom is healthy
59
B
60
A, B, C
61
C, D
62
E
63
D
64
A, C, D
65
D
66
D
67
C, D
68
B = 2/3
69
B, D
70
D = all of them
71
A, C, D
72
C
73
C
74
A, B, C
75
B
76
D
77
B
78
A, D
A -- Miescher coined the term nuclein
B is correct
C is correct
D -- no, A = T, G=C
79
B, C, D
maybe A if it says its 46
80
B
81
D
82
B, C
A is wrong = INCOMPLETE penetrance
D is wrong = must be >18
83
All are correct = A, B, C
84
A
MODY = Maturity-Onset Diabetes of the Young
85
B, C, D
A is wrong = large increase
86
2, 7, 9, 10
87
B is correct, not sure about A but in lectures it says something about 2/3 so maybe A is correct too
C is wrong
= intrachromosal recombination = recombination events within the same chromosome, such as between inverted repeats. In hemophilia A, a well-known intrachromosomal recombination between intron 22 repeats in the F8 gene causes a common inversion.
D is wrong
CMT is caused by large DUPLICATION, not deletion
This duplication results in overexpression of PMP22, disrupting the normal function of peripheral nerves
88
A, B
C is wrong --> Heterozygosity
D is wrong
89
A, C
90
no idea
PPV is 100% if there is complete penetrance
I'd say C is true, chatGPT also said B is true...
91
B
92
B
C s not right = >80% of familial breast & ovarian cancer
Maybe question not written correctly,
acc to chatGPT:
Breast cancer affects about 7% of all women by age 70 — this is roughly correct for the general population, not specifically BRCA mutation carriers. So this statement applies broadly but not as a fact about BRCA.
BRCA1 and BRCA2 mutations significantly increase the risk for breast and ovarian cancer
BRCA mutations are estimated to be responsible for about 5-10% of all breast cancer cases.
93
A
94
C
95
A
96
A, D
Minor anomaly = does not increase mortality
Major anomaly = needs specific treatment
Hypertelorism = wide-set eyes
Hypotelorism = close-set eyes
97
A, B, C
= all except CFTR
98
A, B, D
99
A, B, C
100
A, C
101
A, C, D
102
B
103
B
104
B
105
A, D
106
C
107
B, D
108
A, B, D
109
A
110
A, C
111
B, C
112
B
113
B
114
B
115
C
Acc to ChatGPT, "A" is also possible
B & D are caused by deletions, not by imprinting
Uniparental disomy (UPD) = both copies of a chromosome (or part of it) come from one parent
116
A
117
A
118
119
C, E
Isolated malformations = one or abnormalities of ONE organ/organ system
120
A, B, C
121
A, B, D
"Wild type" refers to the most common or "normal" allele in a population
Newborn screening typically uses biochemical tests, not DNA.
In CGH, patient's sample is mixed with a reference sample (TRUE!):
Patient DNA is labeled (e.g., green)
Reference DNA is labeled (e.g., red)
Both are co-hybridized to a microarray
122
A, B, D
"Wild type" refers to the most common or "normal" allele in a population
Newborn screening typically uses biochemical tests, not DNA.
In CGH, patient's sample is mixed with a reference sample (TRUE!):
Patient DNA is labeled (e.g., green)
Reference DNA is labeled (e.g., red)
Both are co-hybridized to a microarray
123
B, C, D
124
A
125
A, B, D
= all except CFTR
Homozygous HFE pC282Y mutation = 2 red X's
Heterozygous HJV/HAMP/... mutation = 1 orange X
126
A, B
127
B
128
A -- true
B -- false
C -- true
D -- true
129
A, C, D
A not sure...
B is wrong: 150-300
130
A, C, D
131
Which detects microdeletion/ microduplications?
- FISH
- Sanger sequencing
- G banding (karyotype)
- qualitative PCR
- quantitative PCR
132
Clinical sensitivity
a. should be stated on the genetic screening document.
b. do not depend on the mutation type.
c. depend on the population size
d. is the proportion of positive tests if the disease is present.
d. is the proportion of positive tests if the disease is present.
133
What is the mode of action of sulfonylureas?
a. SUR1 subunit
b. KIR.4 subunit
c. Glut channel
a. SUR1 subunit
134
Chance for a fragile X syndrome mom to have an affected son
- 25%
- 50%
- 0%
Fragile X syndrome = X-linked dominant
it says here 50% affected in boys, carriers in daughters
A mother with the full mutation on one X chromosome has a 50% chance of passing that affected X to each child
Sons who inherit the affected X will have Fragile X syndrome (because males have only one X)
Daughters who inherit the affected X will be carriers or affected, depending on X-inactivation.
135
Choose the mitochondrial-inherited diseases
a) Leigh syndrome
B) Sengers syndrome
only A & B
136
Choose wrong statement
a. Missense/nonsense is the most frequent mutation
b. Complex rearrangements are the least frequent
c. Small deletions occur more than small insertions
d. Small insertions occur more than splicing
D acc to chatGPT
B is true acc to lectures
137
Name the chromosomes got affected for
Edwards syndrome
Patau syndrome
DiGeorge syndrome
Williams syndrome
Edwards → 18
Patau → 13
DiGeorge → del(22)(q11)
WIlliams → del(7)(q11)
138
Father has hemophilia A (+ no info about mother), what is the chance that the next offspring will be an affected son
a. 100%
b. 0%
c. 12.5%
d. 6.25%
e. 50%
B
139
Features of MODY (mcq):
a. Obesity is typical
b. primary ß cell dysfunction
c. clinically heterogenous
d. often not recognized
B, C, D
140
How do you mark inbreeding in the pedigree?
= double line
141
How do you test effectivity treatment of CF
= 2 methods:
1. measuring the absolute change in percentage of predicted FEV1 over time (should increase).
2. Cl-test in sweat
142
List 3 genetic causes of male infertility
Klinefelter syndrome
Androgen insensitivity syndrome
Kallman syndrome
Microdeletion in azoospermia factor (AZF) locus
CFTR gene mutation
143
List 3 types of oligogenic inheritance where there is protein interaction
1. Direct interaction
2. Complex
3. Poison
144
List 5 of Wilson and Jungner's principles
1. Condition is an important health problem
2. There should be accepted treatment for patients with a recognized disease
3. Facilities for diagnosis & treatment should be available
4. There should be a suitable test or examination
5. The test should be acceptable to the population
145
List minimum 5 characteristics of Down syndrome
Facial dysmophism (flat face & occiput), upward slanting eyes
Mental retardation
Congenital heart disease
Leukemia
Duodenal atresia
146
List the 9 types of the genetic tests
Diagnostic
Predictive
Presymptomatic
Carrier
Newborn screening
Prenatal diagnosis
Preimplantational diagnosis
Pharmacogenetic teating
Prognostic testing
147
One parent is a carrier of balanced translocation e.g. 11,9, what is the chance for unbalanced offspring
a. 25%
b. 50%
B
148
Presymptomatic/predictive test can be for:
-breast cancer
-Huntington
-both
-none
Both
149
Question about CF mutation classes (read)
= 6 classes of CFTR mutations
Classes 1-3 = severe CF with little/no functional CFTR
Classes 4-6 = milder CF
Class 1 = no synthesis
Class 2 = block in processing
Class 3 = block in regulation
Class 4 = less conduction
Class 5 = less synthesis
Class 6 = reduced half-life
150
Question about syndromology
151
Upd/ Russel Silver syndrome
152
Regarding MODY what is true
a. K channel is a heterotetrametric
b. SUR1 is a part of K channel
c. the drug connects to..?
B
K+ channel is OCTAMER not tetramer (but it is hetero...)
153
the level of action implied in each PGx label can be categorized into?
1. Genetic testing required
2. Genetic testing recommended
3. Actionable PGx
4. Informative PGx
= pharmacogenetics way of labelling drugs
154
What enzyme is responsible for Smith-Lemli-Opitz?
= 7-dehydrocholestrol reductase (DHCR7)
155
What is the most common microdeletion syndrome
= DiGeorge syndrome
156
What small mutation is most likely to be pathogenic?
Deletion / frame-shift mutation
157
Which genotype will need the lowest dose of Warfarin?
A
158
Which hemochromatois type has the most hepcidin expression?
a) HFE deficiency
b) Tfr2 deficiency
c) HJV deficiency
d) FPN mutation
D
159
Which is NOT the phase I enzyme:
a. N-acetyl-transferase
b. Alcohol dehydrogenase
c. Monoamine oxidase
d. Cytochrome P450s.
A
160
Which of the following are triplet expansion disorders?
a. Myotonic dystrophy
b. Friedreich ataxia
c. Huntington's diseasee
A, B, C
161
Which one is a quantitative disorder?
a. Cleft-palate
b. Ischemic heart disease
B
Cleft palate is a QUALITATIVE disorder
162
Write 4 aspects of evaluating lab reports
163
Write 4 characteristics of Turner's syndrome
Write 4 characteristics of Turner's syndrome
45, X (or 46 X, i(Xq))
1. Infertility
2. Low hairline at back
3. Primary amenorrhea
4. Broad chest, widely spaced nipples
5. Heart & kidney abnormalities
164
Write an example of a poor metabolizer
TMPT*2
TMPT*3A
TMPT*3B
TMPT*3C
165
Write down 2 methods of prep of NGS
Hybridization method
Amplicon-based method
166
Write down the genotype of a son with X-linked dominant disease
46XaY
167
Write the genotype of male affected with recessive disorder with X-linked inheritance
46XaY
