Qbank Nuggets Flashcards
(145 cards)
1
Q
What are G bands in a karyotype?
A
AT rich, relatively later replication, and gene rich regions of chromosomes
2
Q
What are R bands in karyotype?
A
GC rich areas, gene poor, early replicating
3
Q
Karyotype: G vs R bands
A
G positive (R negative) bands are AT rich, gene rich, late replicating, tissue specific genes
R positive (G negative) bands are GC rich, gene poor, early replicating, housekeeping genes
4
Q
What percent of trisomy 21 conceptions result in birth?
A
20%
5
Q
What is the most common non-robertsonian translocation seen in constitutional cytogenetics studies?
A
t(11:22)(q23,q11.2)
-
6
Q
Which prenatal study can detect onfined placental mosiacism?
A
CVS (gets sample from placenta)
7
Q
How many chiasma should be present during homologous recombination
A
1 per arm -> 2 per chromosome
8
Q
which aneuploidy is 100% maternal meiosis error?
A
Trisomy 16
Trisomy 18 and 21 are 97% and 90% maternal
9
Q
cancer associated with t(8;21)(q22;q22)
A
AML
10
Q
cancer associated with t(15;17)(q22;q21)
A
Acute promyelocitic leukemia
11
Q
Cancer associated t(12;21)(p13;q22) and t(4;11)(q21;q23)
A
B-ALL
12
Q
3.7mb 17p11.2 duplication
A
Potoki-Lupuski syndrome
(duplication of RAI1)
neurodevelopmental, ASD, apraxia, sleep abnormalities, CHD, growth hormone deficiency
13
Q
17p13.3 deletion
A
Miller-Dieker
LIS1 + dysmorphic featuers
14
Q
Replication slippage
Fork stalling and template switching
Non-homologous end joining
A
Mechanisms of non-recurrent CNVs
15
Q
What is the risk of CVS before 10 weeks?
A
Limb reduction defects and oromandibular hypogenesis
16
Q
What is a common cause of death in CDLS?
A
GI malrotation/volvulus
17
Q
high phytanic acid, low plasmalogens
A
RCDP type 1
PEX7
- Other RCDPs have normal phytanic acid
18
Q
What is a serum biomarker for ataxia telangiectasia?
A
AFP is elevated in 95% of patients
19
Q
What phenotype is a patient with 2 null alleles for SERPINA 1 expected to have?
A
Emphysema
No liver disease -> cannot have toxic buildup
20
Q
What does 5p deletion cause? 5q?
A
5p deletion = cri du chat (cat’s purr)
5q deletion = sotos (NSD1)
21
Q
What aneuploidy is more likely to be a meiosis 2 error?
A
Trisomy 18
22
Q
What does mosiac fragile X look like on southern blot?
A
A 2.8kb band (normal - unmethylated, unexpanded) and smear of methylated bands >6.6kb
- expanded frm1 is unstable
- methylated, nonexpanded alleles = 5.2kb
23
Q
What does poly T tract in CFTR do?
A
T tract is in exon 8 and affect splicing of exon 9
24
Q
What is the length of human genome in cM?
A
~3700cM on average
Female > male
25
Is SMN1 telomeric or centromeric to SMN2?
SMN1 is telormeric
26
How does UV light damage DNA?
Create pyrimidine dimers within strand
27
What is the most common mechanism of false positive MLPA result?
SNP at probe site -\> poor binding of probe/ligation -\> looks like a single exon deletion
28
What does 22q13del cause
Phelan Mcdermid
SHANK3 critical gene
terminal 22deletion
- hypotonia, DD, large fleshy hands, dysplastic toenails
29
hypotonia, DD, **large fleshy hands, dysplastic toenails**
Phelan Mcdermid
SHANK3
22q13 (terminal) deletion
30
What can ringed chromosome 22 be associated with?
NF2
- Unstable ring -\> loss of ch22 (1 hit in 2 hit hypothesis)
31
What does arr(X)x1,(Y)x0[0.2] mean?
arr(X)x1,**(Y)x0[0.2]**
Array: Mosaic turner 45,X/46,X,Y with **Y loss in 20% of cells**
32
What does NM\_002024.5:c.(-231\_-20)ins(1800\_2400) mean?
This is nomenclature for repeat expansion -\> insertion of 600bp repeat -\> 200 trinucleotide repeats
This might be consistent with fragile X
33
NM\_0000511.3:c.[73-2A\>G];[193del] mean? What about NM\_0000511.3:c.[73-2A\>G](;)[193del]?
NM\_0000511.3:c.[73-2A\>G];[193del] means 2 variants in trans
(;) = phase unknown
34
Flattened vertebrae, leukodystrophy, ID
+ high urine sulfatides
Multiple sulfatase deficiency
SUMF1
- Combination of MPS + XALD symptoms
35
What gene impacts clopidogrel phamacogeneics?
CYP2C19
36
What is the mode of inheritance for malignant hyperthermia?
AD
37
What drug is indicated when someones has CF and **G551D** allele?
Ivacaftor (CFTR potentiator)
38
**Cryptophthalmos,** ear anomalies, midline nasal cleft, wide spaced nipples, cryptorchidism, **syndactyly**
Fraser syndrome
FRAS1
39
**Natal teeth, extra frenula**, ASD, narrow chest, **postaxial-polydactyly**
Ellis Van Crevald Syndrome
EVC
40
**Multiple dislocated joints** (hips, knees, etc), hypertelorism, flat nasal root, prominent forehead, **cylindrical fingers**, shorts stature
Larsen Syndrome
FLBN (filamin B)
41
**Folded ears**, VSP, **imperforate anus**, cryptorchidism, **preaxial polydactyly**
Towns brock
SALL1
42
What does HOXA13 mutations cause?
Hand-foot-uterus syndrome
43
What do Holoprosencephaly, Gorlin, Greig cephalopolysyndactyly, Saathre Chotzen, and Rubinstein Taybi have in common?
**SHH signaling pathway**
Holoprosencephaly (SHH)
Gorlin (PTCH1)
Greig cephalopolysyndactyly (GLI3)
Saathre Chotzen (TWIST)
Rubinstein Taybi (CREBB)
44
Lip pits, Cleft L/P
Van der Woude
IRF6
(severe form = popliteal pterygoid syndrome)
45
Cleft L/P, **lower lip fistula, webbing of skin in back of legs,** bifid scrotum, syndactyly, **pyramidal fold of skin overline nail of hallux**
Popliteal Pterygium syndrome
IRF6
(severe end of vanderwoude spectrum)
46
What repeat expansion is more likely to expand in mom?
Fragile X and Myotonic dystrophy
- Most repeat expansions expand paternally
- **X = maternal**
47
What is the mechanism of common achondroplasia mutation?
Gly380Arg
- Methylation of G of CG dinucleotide results in readout of A -\> leads to TG transition in forward strand
48
What drug can be used to treat KRAS negative tumors?
Imatinib - EGFR inhibitor - upstream of KRAS
- would be useless if KRAS is mutated
49
What is 1-specificity?
What is 1-senstivity?
1- specificity = false positive rate
1-senstivity = false negative rate
50
What is the relationship between coefficient of inbreeding and coefficient of consanguinity?
Inbreeding = 1/2 of consanguinity
51
How do you calculate mutation rate from fitness and population frequency?
mutation rate = frequency x selection
Selection = 1 - Fitness
52
Which disorder of creatine metabolism is X linked?
Creatine transporter
53
What is the best screening modality for non ashkenazi jews at risk for Tay- Sachs?
Serum Hex A (WBC Hex A if pregnant)
- Panels usually do not have non-jewish variants
54
Cathepsin A Deficiency
Galactosialidosis
PPGB
- Lysosomal protease that processes precusors of sialidase and B-galactosidase
55
Cathepsin C
Papillon-Lefevre syndrome
CTSC
- Removes N-terminal dipeptides from proteins
- Keratosis palmoplanaris, **periodontisis**
56
Cathepsin K
Pycnodysotosis
CTSK
- protease involved in bone resporption
- Bone fragility, convex nasal ridge, small jaw, skeletal dysplasia
57
What is inheritance pattern for acute intermittent prophyria?
AD - incomplete penetrance
58
high stool isocoproporphyrin
Porphyria Cutanea Tarda
UROD
59
where is SURF1 located in genome?
Autosomal gene that encodes complex IV assembly
- Most common cause of leigh
60
What is CDG1b?
MPI -\> phosphomannose isomerase; treat with mannose
61
What finding is common on treated infantile Pompe?
Hearing loss and osteopenia
62
high 3-Oh propionate, methylcitrate in UOA
PA
63
Which syndrome is associated with absent radii but intact thumbs?
Thrombocytopenia absent radius
RMB8A
64
What syndrome is rectal prolapse assocaited with?
Cystic Fibrosis
65
What limb anomalies are associated with CDLS?
Ulnar defects
- though can be anything
- Upper \> lower
66
Most common mode of inheritance for hypohidiotic ectodermal dysplasia
XL
67
What is mode of inheritance of Aarskog?
AD
FGD1
68
Macrosomia, coarse facies, post-axial polydactyly
Simpson-Gobani-Behmel
Glypican 3 (XL)
- Overgrowth + polydactyly
+ **Conduction defects**
69
What is a pregnancy related complication of cleidocranial dysplasia?
RUNX2
Increased risk of needing C-section
70
What % of pierre robin sequence is syndromic? What syndrome is most common?
50% syndromic
Half of syndromic = stickler
71
Which clinical feature of non-accidental trauma is not seen in OI?
Retinal hemorrhages
72
What does gefitinib target?
EGFR mutations
73
What does MYO7A mutations cause?
AD -\> Deafness
AR -\> Deafness or Usher
74
What is the common mutation in IKBKG?
Incontinentia pigmenti
80% deletions
75
What causes XL SCID? AR SCID?
IL2RG - XL
ADA - AR
76
What is the significance of TNFR5R13B?
Most common cause of common vairable immunodeficiency (CVID)
77
Soft skin, myopia, hernias, normal joint mobility
Cutis Laxa
FBLN5
78
abnormal teeth and nails
normal hair, skin, and sweat
Witkop syndrome
MSX1
ecterdermal dysplasia with normal hair/skin/sweating
79
TSC + renal cysts
16p deletion
- TSC2 + PKD1
80
Most sensitive screening test for DMD in newborn?
CK levels
81
What are the three most common recessive conditions in in Ashkenazi Jews?
1) Gaucher
2/3) Tay-sachs = CF
4) Familial dysautonomia
5) Canavan
82
leukoplakia + bone marrow failure
Fanconi anemia
83
rhabdomyosarcoma, pulmonary pleuroblasoma, multicystic goiter,
DICER1
84
Leukoplakia, **abnormal nails,** marrow failure
Dyskeratosis Congenita
Most commonly XLinked, TER
- **Telomere shortening analysis**
- fanconi like + abnormal nails
85
What syndromes predispose to hepatoblastoma?
FAP (APC) and Beckwith Weidemann
86
What % of patients with unilateral retinoblastoma carry a germline mutation?
15%
87
Chromophobe renal cancer
Seen in Birt-Hogg-Dube
Foliculin
Renal cancer + hair follicle cancers + pneumothorax
88
Somatic mutation in which gene is founds in myeloproliferative disorder in down syndrome?
GATA1
89
Crizotinib is used to treat tumors with what mutation?
Lung cancer with ALK inversion
90
What is the significance of germline POLE mutations?
Colorectal cancer with **hypermutated tumors**
POLE = polymerase epsilon
91
Most common cause of oligospermia, azoospermia, and obstructive azoospermia.
Oligospermia: balanced translocation
Azoospermia: Aneuploidy
Obstructive: CBAVD
92
What is the increased risk over background of a major congenital malformation when IVF is used?
30%
93
What congenital malformation is a fetus of obese mom at highest relative risk for?
NTD
- also increased Cardiac and CL/P
94
**cryptophthalmos,** midline nasal cleft, cryptorchidism, syndactyly
Fraser syndrome
FRAS1, REM, GRIP1
95
What tissue are prominently affected by HOXA and HOXD genes?
Hands and genitals
96
Spatula shaped fingers, multiple large joint dyslocations, hearing loss
Larsen Syndrome
FLNB
97
dysplastic nails/teeth, heart defect, short limbs, amish
Ellis Van Crevald
EVC
98
XL overgrowth w/ conduction defect and polydactyly
Simpson Gobani Behmel
OFD1
XL
99
What are features of non-motile ciliopathies
Non-motile cilia = developmental signaling
- Polydactyly, RP, renal, CNS
Motile cilia = respiratory/patterning -\> heterotaxy
100
What are features of motile ciliopathies?
Motile cilia = clearance and gradient patterning
Respiratory problems + patterning (kartageners/heterotaxy)
Nonmotile = BBS/Joubert/other named syndromic developmental stuff
101
CFTR G551D
Treat with ivacaftor (keep channel open)
102
What causes benign neontal seizures?
KCNQ2 and Q3
103
Most common genetic cause of AD PTN
BMPR2
104
TNFR5R13B
CVID
105
OCRL
Lowe Syndrome
oculo-cerebral-reno
PI singaling
106
Most common genes for : Eczema, hyper IgE, diarrhea
Hyper IgE syndrome
Stat3 (AD), Dock8 (AR, +viral infections)
107
abnormal teeth/nails with normal hair/sweating
Witkop syndrome
MSX1
108
what do you look for in urine of patients with hypophosphatasia?
High pyridoxal-5-phosphate (blood)
Phosphtidylethanolamine (urine)
109
Epidermolysis bullosa with scarring **below** basement membrane
COL7A
Epidermolysis bullosa dystrophic
110
Epidermolysis bullosa with scarring in **epidermis**
EB Simplex
Keratin 5, Keratin 14
AD
111
Epidermolysis bullosa with scarring **within basement membrane**
Junctional EB
LAMB3, LAMC2, LAMA3
112
Mito disease with arrhythmia, ptosis, gaze palsy
Kearns Sayre
Deletion
113
Neonatal high MMA and HCy, resolves by 6 months
Maternal B12 deficiency
-\> Transient MMA/ HCy
114
metabolic acidosis + high ammonia
Organic Aciduria (IVA, MMA, PA)
115
Suberylglycine in UOA
MCAD
116
SMARCB1 (INI1) and LZTR1
Schwannomatosis
117
posterior subcapsular cataracts
NF2
118
Continguous gene deletion with ADPKD on Ch 16
TSC2
119
CGG repeat
FMR1
200+ full mutation
55+ premutation
120
alpha synuclein
Parkinsons
121
what is biocytin?
Substrate for **biotinidase**, which removes lysine to form biotin
122
SLC25A15
SLC25A13
25A15: Ornitine-citruline transporter (HHH)
25A13: Aspartate malate (citrin)
123
Maroteux Lamy syndrome
MPS VI - ARSB/N-ACETYLGALACTOSAMINE-4-SULFATASE
DS
124
Sly syndrome
MPS VII
B-glucoronidase
HS/DS
125
when should breast MRI/mammo start in BRCA carriers?
MRI at 25
mammo at 30
126
lifetime breast/ovarian cancer risk in BRCA
Breast ~80%
Ovarian ~40%
- Both slightly lower in BRCA2 (70 and 20)
127
Male breast ca risk in BRCA2
10% (2% in BRCA1)
128
most useful indicator in working up short stature?
Growth velocity
129
how do tell which chromosome centromere came from (derivative) in a translocation?
Deletion is usually on the derivative
130
how do you tell apart AD and XL-D inheritance on pedigree?
no male-to-male transmission in XL-dominant
131
oncogene in burkitt lymphoma
8:14 translocation
MYC - ig heavy chain
132
what LOD cutoff shows no recombination in linkage analysis?
\>3.0
133
what is the empiric risk of a fetal sample with type 2 mosiacism (mosaic found in multiple cultures in same sample) having true mosaicism (vs lab artifact)?
20%
134
what type of sequence do restriction endonucleases act on?
palindromic
135
Which stage of meiosis are egg cells arrested?
diplotene of prophase 1
136
Goiter, rhabdomyosarcoma, pleuropulmonary blastoma
DICER1
137
Leukoplakia, abnormal nails, bone marrow failure
dyskeratosis congenita
Telomere shortening
138
**thyorid**, colon, **breast cancer**
PTEN
139
Embryonal Rhabdomyosarcoma
SMARCB1
+ schwannomatosis
140
crizotinib
ALK inhibitor for nsclc with inversion
141
Coefficient of inbreeding vs coefficient of consanguinity
Inbreeding = 1/2 \* consanguinity
Consanguinity = (1/2)n
n= links in chain
142
If woman has one affected child with X-linked lethal disorder, what is the chance she is a carrier?
2/3rd
143
SURF1 mode of inheritance
AR -\> Leigh syndrome, complex IV assembly
144
KCNE1, KCNQ1
Jarvell and Lange Nielson
145
SCN5A, KCNE5
Brugada
