Genetics Flashcards
(105 cards)
1
Q
CBAVD
(congenital bilateral absence of the vas deferens) is a/w what mutation
A
CFTR
cystic fibrosis
2
Q
- acute hemolytic anemia in response to oxidant drugs
- X linked recessive d/o
A
G6PD deficiency
3
Q
blotchy red muscle fibers on Gomori trichrome stain
A
mitochondrial myopathies
fibers are irregular shape and size on cross section ; “ragged red fibers” b/c of accumulation of abnml mitochondria under the sarcolemma
4
Q
mitochondrial mypopathies (3)
A
MERRF: myoclonic epilepsy with ragged red fibers
Leber optic neuropathy (blindness)
MELAS (mitochondrial enceph with stroke-like episodes and lactic acidosis)
5
Q
lyonization
A
x-inactivation
6
Q
condensed heterochromatin: _____ DNA and ____ histones
A
methylated DNA
deacetylated histones
7
Q
pleiotropy
A
1 gene –> many effects
8
Q
maternal inheritance
variable phenotype
A
heteroplasmy
different amounts of mt mitochondria
9
Q
3 mt sites for early-onset familial alzheimer disease (
A
- Ch 21: amyloid precursor protein (APP) gene
- Ch 14: presenilin 1
- Ch 1: presinillin 2
(all promote production a A beta-amyloid)
10
Q
Late-onset Alzheimer disease allele
A
E4 allele of Apoliprotein E
ApoE4 may be involved in senile plaque formation
11
Q
Hypertrophic cardiomyopathy
A
AD
beta-myosin heavy chain mt
12
Q
Hemeatologic risks in down synd
A
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
13
Q
1st and 2nd MCC of congenital mental retardation
A
- Downs
2. Fragile X
14
Q
Fragile X genetics
A
X linked
CGG trinuc repeats
FMR-1 gene on long arm of X
when cultured in folate-def medium, area of incrased repeats does not stain and appears “broken”
15
Q
tall stature
gynecomastia
small, firm testes
A
Klinefelter
XXY
16
Q
renal mass
deletion on 3p
A
VHL
17
Q
majority of nondisjunction events (for tri 21) occur….
A
meiosis 1
18
Q
prominent occiput micrognathia small mouth low-set and malformed ears rocker-bottom feet
A
Tri 18
Edwards
19
Q
clenched hands with index finger overriding the middle finger and fifth overriding the fourth
A
Tri 18
Edward
20
Q
cleft lip and palate polydactyly microcephaly/holoprosencephaly rocker-bottom feet umbilical hernia cardiac defects renal defects
A
Tri 13
Patau
21
Q
stillborn:
edematous hands and feet
cystic hygroma of the neck
coartation of the aorta
A
stillborn Turner
45, XO
22
Q
stillborn: flat facial features excessive skin at nape of neck VSD duodenal atresia
A
Tri 21
Down
23
Q
GI a/w Patau (tri 13)
A
abdominal wall defects - omphalocele or ubilical hernia
pyloric stenosis
24
Q
Friedreich’s ataxia (genetics)
A
AR
Frataxin gene (ch 9) - codes for mitochondrial protein important in respiratory function and Fe homestasis
- GAA repeats disrupt trasncription
25
HIV gag
p24
| p7
26
HIV env
gp120
| gp41
27
HIV pol
reverse transcriptase
integrase
protease
28
HIV tat and rev genes
regulatory genes required for viral replication
29
Huntington mech
- AD
- CAG repeats in the huntingtin protein
- expansion of plygutamine region --> GAIN OF FUNCTION mt --> various transcription factors
- thought to be through transcriptional repression silencing
- histone deacetylation --> silencing genes necessary for neuronal survival
30
Fragile X mech
increased CGG trinuc repeats --> hypermethylation of cytosine bases --> gene inactivation
31
when does trinucleotide expansion occur
paternal transmission
| during spermatogenesis
32
Auer rods (gene)
t(15,17)
AML
33
t(15,17)
- AML
- Auer rods
- retinoic acid receptor (17) onto promylelocytic leukemia gene
--> abnl retinoic acid receptr inhibits differentiation of myelobloasts and triggers acute promyelocytic leukemia
34
t(8,14)
Burkett lymphoma
c-myc (proto-onc) -ch8
next to Ig heavy chain
35
t(9,22)
abl (9 to 22)
bcr-abl
tyrosine kinase
"philadelphia chromosome"
chronic myelogenous leukemia
36
t(11,14)
activation of cyclin D
Mantle cell lymphoma
37
deletion of 13q
chronic lymphocytic leukemia (CLL)
38
t(14,18)
bcl-2 (14) and Ig heavy chain
90% of Follicular lymphoma
30% of Diffuse large B-cell lymphoma
39
```
infant
"floppy"
not feeding well
mild jsundice
enlarged tongue
hypotonia
constipation
umbilical hernia
```
congenital hypothyroidsm
40
```
15 y/o
gait instability
frequent falls
kyphoscoliosis
pes cavus
lower extremity ataxia
impaired position/joint sense
(inherited)
```
Friedreich ataxia
41
Friedreich ataxia - areas affected
posterior columns and spinocerebellar tracts of spinal cord
loss of larger sensory cells of dorsal root ganglia
42
Friedrich ataxia - common cause of death
hyerptrophic cardiomyopathy --> arrhythmias and CHF
bulbar dysfunction (unable to protect airway)
43
hypertrophic cardiomyopathy
diabetes mellitus
kyphoscoliosis
foot deformities
Freidreich ataxia
44
bilateral renal masses composed fo fat, smooth muscle, and blood vessels... a/w...
(renal angiomyolipomas)
a/w tuberous sclerosis
may also see:
brain hamartomas
ash-leaf spots
45
Tuberous sclerosis (gen)
AD
46
Tuberous sclerosis symp
- cortical tubers
- subependymal hamartomas in brain--> seizures, mental retardation
- cardiac rhabdomyomas
- facial angiofibromas
- ash-leaf patches
47
pigmented nodules of the iris
Lisch nodules
Neurofibromatosis type 1
48
cafe au lait spots
neurofibromatosis type 1
49
optic gliomas
neurofibromatosis type 1
50
bilateral acoustic neuromas
neurofibromatosis type 2
51
meningiomas, gliomas, ependymomas of the spinal cord
neurofibromatosis type 2
52
neurofibromas
neurofibromatosis type 1
53
cerebellar hemangioblastomoas
retinal hemangiomas
liver cysts
VHL
54
leptomeningieal capillary-venous malformation
Sturge-Weber
| also port wine stain
55
multiple telangiectasias of the skin and mucosa --> recurrent epistaxis or GI bleeding (melena)
Osler-Rendu-Weber
| hereditary hemorrhagic telangiectasia
56
location of tangles and plaques in Alzheimers
| generally
INTRAcellular neurofibrillary tangles
EXTRAcellular A-beta-amyloid plaques
57
composition of intracellular neurofibrillary tangles in Alzheimers
tau protein:
| a primary component of intracellular microtubules
58
what is the normal function of amyloid precursor protein (APP)
involved in synaptic formation and repair
59
which is more specific to alzheimer's - tangles or plaques?
tangles
- only in Alzheimer's dementia
(amyloid plaques may be present in other neurodegen d/o and normal adults)
60
tri 21 quad screen
low AFP
HIGH beta-hCG
low estriol
HIGH inhbin A
61
achondroplasia genetics
```
AD
GAIN of function mt
FGFR3 gene (fibroblast growth factor receptor 3)
```
85% sporadic mutation due to advanced paternal age
62
complete hydatidaform mole:
```
ploidy
uterus size
hCG levels
tissue
risk of malignancy
```
diploid
uterus -"size greater than dates"
hCG - extremely high
tissue - only trophoblast
Malignancy risk - 15-20%
63
partial hydatidiform mole
```
ploidy
uterus size
hCG levels
tissue
risk of malignancy
```
triploid
uterus - normal size
hCG - high normal
tissue - fetal parts present
malignancy risk - low (
64
location of promoters
25-70 bases upstream from the gene
65
maternal virulization during pregnancy and ambiguous XX genetalia
placental aromatase deficiency
66
5' prime post trascriptional mod
5' guanasine cap
5' cap methylation
= 7-methyl-guanosine cap
67
order of post translational mod
```
hnRNA (pre mRNA)
1) 5'cap
2) Poly A tail
Introns
3) intron removal
```
68
BRCA 1&2
- DNA repair genes
- Breast and ovarian cancer
- 2 hit LOF
69
APC/beta-catenin
-wnt signalling pathway
- colon cancer
- gastric cancer
- pancreatic cancer
- Familial adenomatous polyposis (Lynch?)
-2 hit LOF
70
TP53
-genomic stability
- most cancers
- Li-Fraumeni syndrome
- 2 hit LOF
71
RB
G1/S transition inhibitor
- retinoblastoma
- osteosarcoma
2 hit LOF
72
WT1
urogenital differentiation
- Wilms tumor
2 hit LOF
73
VHL
ubiquitin ligase component
- renal cell carcinoma
- Von Hippel-Lindau syndrome
2 hit LOF
74
order of enzymes in BASE excision repair
-glycosylase: recognize abnormal base and cleave from DNA molecule --> AP site (apurinic/apyrimidinic)
- endonuclease:
cleaves 5' end of AP site
- lyase or phosphodiesterase:
completes extraction of AP site by removing sugar-phosphate base
- DNA polymerase
- ligase
75
DNA damage from dietary nitrites
deamination of
cytosine --> uracil adenine -->hyoxanthine
guanine --> xanthine
76
Genetics for MCC of hair loss
(androgenic alopecia)
polygenic
variable penetrance
77
genomic change due to 1 base pair deletion resulting in changed/ineffective protein
frameshift
| vs nonsense, which is a substitution
78
neonate w/ lymphadema and cystic hygromas
turner (XO)
79
de novo partial deletion of chromosome 5
| 5p-
cri du chat
round face
catlike cry
microcephaly
80
round face
catlike cry
microcephaly
cri du chat
| 5p-
usually de novo
81
Kallmann genetics
mt in KAL-1 gene or
| fibroblast growth factor receptor 1 gene
82
delayed puberty
absence or incomplete dev of secondary sex characteristics by:
14 in boys
12 in girls
83
first sign of putberty
boys - testicular enlargement
girls - breast enlargement
84
3 cytogenic abnormalities that produce Down Syndrome
- Tri 21 (95%)
- Unbalanced Robertsonian translocation (2-3%)
- Mosaicism
85
proteins that can bind DNA (examples)
- transcription factors
- steroids
- thyroid proteins
- vit D receptors
- retinoic acid receptors
(others)
86
MYC proteins
mammalian transcription factors
| e.g. c-myc is overexpressed in Burkitt lymphoma
87
imprinting
methylation of cytosine residues
88
X linked lysosmal storage diseases
Fabry
| Hunter
89
Lesch-Nyhan genetics
X-linked Recessive
| deficiency of hyoxanthine phosporibosyltransferase
hyoxanthine-->IMP
guanine --> GMP
purine salvage
90
Leber hereditary optic neuropathy genetics
mitochondrial
91
Hemophilia B genetics
X-linked recessive
| factor IX def
92
classical galactosemia genetics
AR
93
typical inheritance pattern for enzyme deficiencies
AR
94
typical inheritance pattern for defective non-catalytic proteins
AD
95
```
tall stature
gyneocomastia
azoospermia
behavior problems
intellectual disability
```
Klinefelter
96
recognize
UGA
UAA
UAG
releasing factors
97
Meyer-Rokitascky-Kuster-Hauser (MRKH) syndrome
mullerian aplasia/vaginal agenesis
- no upper vagina
- variable uterine development
- normal ovaries
- normal dev of secondary sexual characteristics
- primary amenorrhea
- 50% of any mullerian defects (e.g. unicornate, bicornate, septate uterus) a/w urologic anomalies
(e. g. renal agenesis)
98
co-infection results in progeny that contain nucleocapsid from one strain and genome of the other;
next generation revert to original, unmixed
phenotype mixing
99
uptake of naked DNA
transformation
100
RAS
GTP binding protein
- cholangiocarcinoma
- pancreatic adenocarcinoma
1 hit GOF
101
MYC
transcription factor
- Burkitt lymphoma
1 hit GOF
102
ERBB1 (EGFR)
receptor tyrosine kinase
- lung adenocarcinoma
1 hit GOF
103
ERBB3 (HER2)
receptor tyrosine kinase
- breast cancer
1 hit GOF
104
ABL
nonreceptor tyrosine kinase
- chronic myelogenous leukemia (CML)
1 hit GOF
105
BRAF
RAS signal transduction
- hairy cell leukemia
- melenoma
1 hit GOF
