Genetics - Martin Flashcards
1
Q
Missense
A
change 1 base = different protein
2
Q
Nonsense
A
change 1 base = stop codon
3
Q
CF is what type of d and how are heterozygote carriers in risk of things
A
Autosomal recessive
- in risk of pulmonary or pancratic
4
Q
CF genes mutations that are not the actual gene mutation for CFTR can cause
A
- in risk of pulmonary or neonatal meconium ileus (thick hard to pass)
5
Q
PKU common in
A
scandinavian
NOT AA or jews
6
Q
PKU deficiency in
causing
when do sx start
A
Phenylalanine hydroxylase (PAH) deficiency = hyperphenalaniemia
X tyrosin
at 6mo
7
Q
PKU sx
A
intellectual disability
hypopigmentation hair, skin, eczema
musty odor
8
Q
2 X linked DZ
A
- G6PD deficiency
2. Fragile X syndrome
9
Q
autosomal dominant
A
- HD
- neurofibromatosis
- marfan syndrome
- Ehlers-Danlos syndrome
- Osteogenesis imperfecta
- Familial hypercholesterolemia
10
Q
autosomal recessive 2 DZ
A
- CF
2. PKU
11
Q
Galactosemia
A
X galactose-1-phosphate uridyltransferase = accumulation of galactose
12
Q
albinism
A
low TRY = X melanin
13
Q
Lesch-Nyhan
A
high intermediate product that breaks down to toxic product
14
Q
a-antitrypsin deficiency
A
X neutrophil elastase in lung = emphysema
* avoid smoking
15
Q
reason for a-antitrypsin deficiency
A
mutated PIZZ
- in risk of emphysema, hepatocellular carcinoma = liver transplant
16
Q
Thalassemia
A
effects amount of globin chains made for Hb
17
Q
drugs and enzyme deficiency
A
some drugs can unmark a deficient enzyme in a person
= Antimalarial primaquine = severe hemolytic anemia (from G6PD deficiency)
18
Q
Marfan Syndrome defected gene and chr
A
FBN1 = X fibrillin-1 (ECM glycoprotein)
chr 15q21.1
19
Q
X fibrillin leads to
A
- loss of structural support
2. excessive activation of TGF-B
20
Q
high TGF-B SX
A
- bony overgrowth, myxoid changes in mitral valve
2. inflammation, vascualr SM, high MMPs (metalloproteases)
21
Q
Marfan Syndrome SX
A
- congential contractural arachnodactyly
- tall, long extremities
- double jointed, hyperextension
- Dolicocephalic (long- headed), frontal bossing,
prominant supraorbtial ridges - pectus excavatum (depressed sternum)
- ectopic lentis (lens dislocation)*
- mitral valve prolapse, dialted distended ascending aorta = aortic dissection
22
Q
Ehlers- Danlos Syndromes (EDS) reason
A
defect in collagen synthesis
23
Q
Ehlers- Danlos Syndromes (EDS) SX
A
- hyperextensive skin, hypermobile joints
- fragile skin brusing
- gaping defects (hard to heal surgery)
- colon or Large As rupture,
- rupture of cornea, retinal detachment
24
Q
classic EDS
A
diaphragmatic hernia
= AD
25
vascular EDS
colon or Large As rupture,
| =AD
26
Kyphoscolisis EDS
rupture of cornea, retinal detachment
= AR
= PLODI gene
27
Dermatosparaxis EDS
= ADAMTS2 gene
28
Familal Hypercholestrolemia
| due to
1. mutated LDL Receptor
2. ApoB problem (ligand)
3. PCSK9 problem : remove LDL form liver
29
Familal Hypercholestrolemia heterozygoze
2-3 X higher cholesterol + CAD
| = Tendinous xanthomas
30
Familal Hypercholestrolemia homozygous
5-6X higher plasma cholesterol
| = skin xanthomas, coronary , cerebral atherosclerosis , MI before 20yo
31
Lysosomal Storage Disease : Gaucher Disease in risk of getting
Parkinsion's D
32
Lysosomal Storage Disease : Niemann- Pick type C in risk of getting
Alzheimer's D
33
Autophagy
turnover dysfunctional mitochondria = mitophagy
34
impaired autophagy gives rise to
2ndaryt accumulation of lysosomes = neurodegenerative link
35
primary accumulation of lysosomes =
large lysosomes stuffed, due to enzyme not present
36
TX of lysosomal diseases
1. enzyme replacement therapy
2. "substrate reduction therapy: reduce substate unable to get degraded
3. molecular chaperone therapy: a misfolded enzyme when bound to competitive inhibitor can cause proper folding of it to occur
37
Gaucher cell looks
crumpled tissue paper
38
Globoid cells seen in
Krabbe's disease
39
Niemann-Pick disease cells
1. Zebra bodies
| 2. Foam cells (bubble appearence)
40
Tay-Sach's disease cells
onion skin whorled lysosomal membranes in EM
| lipid vacuoles also in neurons
41
Lysosomal diseases 4
1. Tay-Sachs
2. Gaucher
3. Niemann pick
4. MPSs (Hurler)
42
Tay-Sachs reason and most likely to get it
X Hexosaminidase A (HEXA) from mutation of chr 15
| Jews, east euopeans
43
Tay-Sachs causes
gangliosidosis GM2
44
Tay-Sachs SX
at 6mo
motor and mental disorientation, flacciditym blind, dementia
= average age is 2-3 yo
45
Tay-Sachs on eye
Cherry-red spot on macula
46
Tay-Sachs accumulation of
ganglioside in neurons, eye, heart, liver , spleen
| = fat stains oil red O+ Sudan black B
47
Niemann- Pick DZ reason
| common in
X sphingomyelinase
= accumulation of sphingomyelin in lysosomes
(Chr 11p15.4)
Jews
48
Niemann- Pick Type A :
severe infantile, COMPLETE x spingomyelinase
- neuro issues
- a lot of accumulation
- death before 3yo, sx by 6mo
49
Niemann- Pick Type B :
least severe
- organomegaly
- NORMAL CNS
- live to adult
50
Niemann- Pick type C :
intermediate severe, most common
- NPC1 mutation,
- progressive CNS change
- ataxia, palsy, dystonia
51
zebra bodies are
lysosomes with concentric lamellations
52
Niemann- Pick eye and 2 other special things you see
1. Cherry red retinal spot -type A
2. massive splenomegally
3. lipid accumulation in cerebellum
53
Gaucher Disease reason
X Glucocerebrosidase = accumulation of glucocerebroside in phagocytes (involves BM) or CNS
= M ACTIVATION - IL1, IL6, TNF
54
Gaucher Disease Type 1 :
least severe
- chronic nonneronpathic
- NORMAL CNS
- spleenomegally
- bone sx
- jews
55
Gaucher Disease Type 2 :
most severe
- acute neuropathic
- infantile cerebral pattern, progressive CNS problems
- early death
- hepatospleenomegally
- NOT JEWS
56
Gaucher Disease Type 3 :
intermediate
- progressive CNS
- begins at adolescence or early adulthood
57
Gaucher Disease special things you see 4
1. 10Kg spleen
2. BM erosion , bone sx
3. pancytopenia
4. thrombocytopenia
58
Gaucher cells
distended phagocytic cells
59
Gaucher Disease TX
allogenic hematopoietic stem cells transplant
60
Mucopolysaccharidoses (MPS)
| reason and 2 types
X glycosaminoglycas
= a lot of ground substance of CT
1. Hurler
2. Hunter
61
Mucopolysaccharidoses (MPS) SX
coarse facial features, clouding of cornea, stiff joints, intellectually problems
Hepatospleenomegaly, valvular leasions, brain lesions
62
Hurler specific SX:
```
MPS I-H : X a-L-iduronidase,
-normal at birth
-hepatopleenomegaly by 6-24mo
- death at 6-10yo (cardiac problems, coronary deposits)
- corneal clouding
(AR)
```
63
Hunters specific SX:
MPS II: X iduronate-2-sulfatase
- NORMAL cornea
- milder then hurlers
(X-linked)
64
Mucopolysaccharidoses (MPS) are
mononuclear phagocytic cells
65
Mucopolysaccharidoses (MPS) cells and histology
1. lamellated Zebra bodies also
| 2. balloon cells : clear cytoplasm, many vacuoles = swollen lysosomes ----> PAS +
66
Mucopolysaccharidoses (MPS) most common cause of death
MI, cardiac decomposition
67
Glycogenoses, Glycogen storage disease usually involves what organs
liver or muscle
68
Glycogenoses : Hepatic form
VON- Gierke
| high glycogen storage in liver = hypoglycemia
69
VON- Gierke
X Glucose-phosphatase , no release of glucose from the liver
70
Glycogenoses : Myopathic form
McArdle
high glycogen storage in muscles
muscle weakness, cramps after exercise
(* NO blood lactate after exercise)
71
McArdle
X Phosphofructokinase (PFK) , phospholylase in muscles
72
Glycogenoses : Miscellaneous
```
Pompe
1. X acid a-glucosidase (acid maltase)
2. X branching enzymes
= cant store glycogen
- early death
```
73
Pompe
X acid maltase (acid a-glucosidase)
| = cardiomegaly
74
low amounts of :
in Von Gierke
in McArdle
low glucose in blood (hypoglycemia)
| low energy output
75
Pompe cells
glycogen filled cardiac cells
76
most common cause of congenital malformation
environment enhancing genetic problems
| = range of severity of disorder due to environment and many factors involved
77
reducing neural tube defects can be done by
ADD FOLIC ACID in diet of mother
78
Euploid
exact multiple of haploid 23 number
79
Aneuploid
chr not multiple of 23
- nondisjunction : +/- 1 chr
- anaphase lag : during meiosis or mitosis, one chr lags behind and left out = 1 normal cell and 1 monosomy cell
80
Monosomy
too much loss of DNA to have live birth except some trisomies that still do
81
Mosaicism
mitotic errors in early development = 2 or more populations of cells with different chromosomal complement
82
Mosaicism usually effect
sex chr
83
ring chr
break at both ends of chr + fusion of damaged ends = 46XY, r(14)
84
Inversion
rearrangement involving 2 breaks in 1 chr + inverted intervening segments
85
isochromosome :
1 arm of chr is lost, remaining arm is duplicated
| = chr has 2 long arms or chr has 2 short arms
86
Balanced reciprocal translocation
1 break in 2 chr, exchange in material + no loss in material
87
Roberstsonian translocation
translocation between 2 acrocentric chr (closer to centromere
=**** transfer of 1 very large chr + 1 very small chr
= small one usually lost
= normal phenotype
= 1 in 1000 normal people
88
trisomy 21 Roberstsonian translocation
3-4%*
- q arm of chr 21 is translocated to another chr
- fetus has 46chr with 3 copies of chr 21 long arm ****
89
SX of Trisomy 21
1. epicanthal folds, slanted palpebral fissures, flat face
2. brushfield spots on iris
3. simian crease + clinodactyly on hands
4. gap between big toe
5. small hypoplastic ears
6. fissured tongue
90
Trisomy 21 Down syndrome
47chr
| - huge maternal age factor (1/1550 under 20yo, 1 in 25 in over 45yo), since extra chr is maternal origin
91
Trisomy 21 Down syndrome RISKS
1. congenital heart D (40%), AVSD,****
2. acute myeloid leukemia 500X chance, 20X chance acute B lymphoblastic leukemia
3. Alzheimers (at 40yo almost all)
4. serious lung or thyroid infections
92
chr 21 is usually coding for
mitochondria functions -ROS, apoptosis
amyloid proteins - alzheimers
IncRNAs
93
how to screen for congential malformations
maternal blood, which has 5-10% fetal blood
94
Trisomy 18
Edwards
- congenital heart problems
- horse shoe kidney
- intellectual problems
95
Trisomy 13
Patau
- cleft lip
- microphthalmia
- cardiac defects
- renal defects
- intellectual disability
96
Chr 22q11.2 Deletion Syndrome
1. DiGeorge Syndrome
| 2. Velocardiofacial syndrome
97
1. DiGeorges Syndrome : SX
- thymic hypoplasia = T-cell immunodeficiency *
- parathyroid hypoplasia = hypocalcemia*, cardiac malformation
- allergic rhinitis, thrombocytopenia can be seen
- Cleft palate
98
2. Velocardiofacial syndrome : SX
- facial dysmorphism (prominent nose, retroganathia, long face, pear nose), cleft palate,
- cardiovascular anomalies
- learning disabilities
99
Lyonization
inactivation of all except 1 X chr
100
Lyon hypothesis
1 X is active
| all others --> heteropyknosis, inactivate (random) = Barr body
101
Barr body genes
most are inactive, some escape inactivation
102
Klinefelter syndrome SX
47 XXY -> male
hypogonadism
dx after puberty
long legs, small testes, small penis, X secondary male characteristics, low spermatogenesis, gynecomastia
103
Klinefelter syndrome risk for
1. T2D, metabolic syndrome
2. mitral valve prolapse
3. germ cell tumors, teratomas
4. breast cancer
5. SLE
104
Turner's syndrome
```
45 X female
Webbing of neck* + low posterior neck line*
broad chest
Streak fibrotic ovaries *
amenorrhea most common cause*
hypogonadism, short
partial monosomy
```
105
Turners syndrome risks
- some have there X chr with Y-chr genes = gonadoblastoma
- Cystic hygroma : edema infant from lymph stasis in neck
- Congenital heart disease (LEFT), coarctation
- Hypothyroidism *
- glucose intolerance, obesity, insulin resistance (few)
106
Turners syndrome TX
estradiol given
107
true hermaphrodite
both ovarian and testicular tissue are present
108
pseudohermaphrodite
disagreement of phenotypic and gonadal sex
- female pseudohermaphrodite : ovaries + male external genitalia
- male pseudohermaphrodite : testicular tissue + female- type genitalia
109
trinuclear repeats usually cause
```
neurodegenerative disorders (usually G or C)
= accumulation of aggragated mutant proteins in large intranuclear inclusions****
```
110
1. loss of function trinuclear repeat
Fragile X
111
Toxic gain of function trinuclear repeat
HD
112
Toxic gain of function mediated by mRNA trinucelar repeat
Fragile X tremor-ataxia syndrome
113
Fragile X syndrome mutation in and reason it happens
mutated FMR1 gene trinuclear mutation with MANY CGG repeats that expand during oogenesis = loss of function
114
Fragile X syndrome SX
-intellectual disability, aggressive, autism, anxiety, hyperactive, long face, large mandible, large up ears, large testicles (macro-orchidism), hyperflexy, mitral valve prolapse, pectus excavatum
BIG BALLS*
115
Fragile X syndrome inheritance
gets worse in SX and starts earlier each generation (* esp when passed on from female) = anticipation
116
Fragile X syndrome who is effected
males
| females can be effected (Intellectually low)
117
fragile X- associated primary ovarian failure
from gain of function FMR1
| premature ovarian failure
118
fragile X-associated tremor/ataxia
in 6th decade they get this from FMR1 amplification
119
HD SX
AD
dementia, progressive movement disorder, striatal neurons degenerate , chorea,
- HTT (polyglutamine trinucleaotide repeat) *
= accumulated huntingtin
= during spermatogensis
= anticipation
120
LHON (Leber hereditary optic neuropathy)
defect in mitochondria DNA passed from mother
- progressive bilateral X central vision (age 15-35) = blindness
- cardiac conduction defects
121
mt diseases
- threshold effect for any disorder to happen
| - heteroplasmy : both normal and mutant DNA
122
Prader Willi syndrome
intellectual problems, short, obese (cant stop eating, hypotonia, hypogonadism
CHR 15 deleted = paternally
123
Angelman syndrome
intellectual problems, ataxia happy walk, seizures, inappropriate laughter = happy puppets
CHR 15 deleted = maternally
124
imprinting can cause what 3 things
1. Deletion of a chr : like chr 15
2. Uniparental disomy : 2 chr from same parent (chr 15 both from mom - Prader willi syndrome)
3. Defective imprinting : the maternal chr carries the paternal chr = X mom chr, or paternal carries the maternal chr = X dad chr
