Quiz 2: Chromosomal Abnormalities Flashcards
(122 cards)
1
Q
How common are chromosomal abnormalities?
A
1/154 births
2
Q
How common are the 2 types of aneuploidy?
A
X & Y: 1/475, Autosomes: 1/700
3
Q
How common are structural chromosomal abnormalities?
A
1/375, Balanced: 1/500, Unbalanced: 1/1600
4
Q
Where is aneuploidy likely to generate?
A
Meiosis I or II due to Nondisjunction
5
Q
What deletion associated with Cri-du-chat?
A
Deletion in Chromosome 5p
6
Q
What term describes symptoms due to insufficient gene product associated with deletions?
A
Haploinsufficiency
7
Q
How likely is de novo cause of Cri-du-chat?
A
90%
8
Q
Symptoms of Cri-du-chat?
A
1) High Pitched Cry
2) Hypertelorism - wide set eyes
3) Epicanthus
9
Q
Acrocentric chromosome definition
A
Centromere is located near one end of the chromosome
10
Q
Robertsonian translocations occur only between what type of chromosomes?
A
Acrocentric chromosomes
11
Q
What are the acrocentric chromosomes
A
13, 14, 15, 21, 22
12
Q
1q duplicaton syndrome genetics
A
1q duplication; de novo
Non-allelic homologous recombination (NAHR)
13
Q
1q duplicaton syndrome symptoms
A
Developmental delay, small receding jaw
14
Q
22q deletion Inheritance (DiGeorge, velocardiofacial, conotruncal)
A
Dominant (22 is a dominant age)
reduced penetrance and variable expressivity
15
Q
22q deletion genetics
A
3 Mb deletion of 22q; can be inherited, nested deletions usually
16
Q
22q deletion Sx
A
1) Congenital heart defect
2) palate abnormalities
3) hypocalcemia
17
Q
Achondroplasia Inheritance
A
AD
paternal age effect
incomplete dominance (double-dominant effect)
18
Q
Achondroplasia genetics
A
Point mutation of FGFR3 (fibroblast growth factor receptor)
19
Q
Achondroplasia Sx
A
Reduced bone growth
short stature
20
Q
Androgen insensitivity syndrome Inheritance
A
X linked
21
Q
Androgen insensitivity syndrome Genetics
A
Androgen receptor gene
22
Q
Androgen insensitivity syndrome Sx
A
“Female” physical features form
23
Q
Angelman Inheritance
A
Paternal imprinting, AD
Chromosome 15
24
Q
Angelman Genetics
A
15q deletion or paternal imprinting of that region
25
Angelman Sx
1) developmental delay
2) intellectual disability
3) "happy" demeanor
26
ASD Inheritance
Observed paternal age effect, multifactorial
27
ASD Genetics
CNVs
| Copy Number Variation
28
ASD Sx
social difficulties/delays
29
Campomelic dysplasia Inheritance
| "bent limb"
Sporadic
haploinsufficiency
sporadic genetic disease is not inherited from parents, but arises via a mutation
"bent limbs not a strong spine so insufficient and sporadic"
30
Campomelic dysplasia Genetics
Heterozygous mutation of SOX9 gene
SOX9 very important for development of the skeleton
31
Campomelic dysplasia Sx
1) Skeletal malformation
| 2) gonadal disgenesis in males (testes fail to form, ovaries form)
32
Congenital adrenal hyperplasia Inheritance
AR
33
Congenital adrenal hyperplasia Genetics
Enzymes of adrenal cortex
34
Congenital adrenal hyperplasia Sx
Virilization in XX individuals
35
Crit-du-chat Inheritance
Dominant
haploinsuffiency
36
Crit-du-chat Genetics
5p deletion; 90% de novo
37
Crit-du-chat Sx
1) Cry of the cat sounds
2) microcephaly
3) epicanthal folds
4) intellectual disability
38
Cystic fibrosis Inheritance
AR, 1/23 white individuals is a carrier
39
Cystic fibrosis Genetics
CFTR gene
cystic fibrosis transmembrane conductance regulator
When NOT working, chloride becomes trapped in cells
40
Cystic fibrosis Sx
frequent respiratory infections, gastrointestinal distress,
41
Down syndrome Inheritance
Sporadic, maternal age effect (can be inherited thru balanced translocations like Robertsonian)
42
Down syndrome Genetics
Trisomy 21 (nondisjunction)
43
Down syndrome Sx
1) Craniofacial features
2) intellectual disability
3) stunted growth
4) congenital heart defects
44
Duchenne Muscular Dystrophy Inheritance
"X-linked
(Carriers can be manifesting heterozygotes)"
"Duschenne loves his mother" - x linked
45
Duchenne Muscular Dystrophy Genetics
Mutation in DMD gene
codes for dystrophin, which strengthens muscle fibers and protects them from injury as muscles contract and relax
46
Duchenne Muscular Dystrophy Sx
Weakness
stiffness
ataxia
scoliosis - curvature of spine
loss of ambulation
47
Edward syndrome Inheritance
Sporadic
maternal age effect (can be inherited thru balanced translocations)
48
Edward syndrome Genetics
Trisomy 18 (nondisjunction)
49
Edwards syndrome Sx
1) Rocker bottom feet
2) intellectual disability
3) receding forehead
4) fist clench
50
Familial hypercholesterolemia Inheritance
"AD
| Present in Afrikanaer population"
51
Familial hypercholesterolemia Genetics
LDLR mutation
When LDL receptors do not function correctly, LDL stays in the bloodstream longer than it should
52
Familial hypercholesterolemia Sx
High cholesterol
xanthomas (fats build up under the surface of the skin)
atherosclerosis
Homozygotes express earlier
53
Fanconi anemia Inheritance
AR (allelic heterogeneity, many are compound heterozygotes)
pretty bad so AR
54
Fanconi anemia Genetics
FANCA frameshift or deletion
FANCA does inter-strand DNA cross-link repair and in the maintenance of normal chromosome stability
Regulates differentiation of haematopoietic stem cells into mature blood cells
55
Fanconi anemia Sx
```
extreme tiredness (due to anemia)
frequent infections (immune cell deficiency)
easy bruising (low platelet)
nose or gum bleeding
```
All due to problems with hematopoeitic stem cell formation
56
Fragile X syndrome Inheritance
X-linked Recessive
Females have milder syndromes
57
Fragile X syndrome Genetics
Fragile site on X
58
Fragile X syndrome Sx
Intellectual disability,
craniofacial features
59
Hemochromatosis Inheritance
AR
reduced penetrance/sex influenced phenotype
(affects males more because of female lifestyle and menstruation/iron loss)
60
Hemochromatosis Genetics
HFE gene mutation (HFe - high iron)
HFE protein regulates hepcidin production.
Hepcidin produced by the liver, determines how much iron is absorbed from the diet and released from storage sites in the body
61
Hemochromatosis Sx
Enhanced iron absorption leading to:
1) cirrhosis
2) impotence (Iron deposition in the pituitary or the gonads leads to hypogonadism)
3) cardiomyopathy
62
Hemophilia A Inheritance
X-linked
63
Hemophilia A Genetics
F8 gene
LINE insertions - insertional mutagenesis is the creation of mutations of DNA by addition of one or more base pairs
64
Hemophilia A Sx
Clotting problems, bleeding disorder
65
Huntington disease Inheritance
AD; anticipation (polyglutamine disorder due to CAG repeat expansion)
66
Huntington disease Genetics
Huntingtin gene (Huntingtin is critical for brain function)
Expansion of CAG repeats
67
Huntington disease Sx
Neurological impairment
abnormal movements
fatal
68
Klinefelter syndrome Inheritance
Sporadic, maternal age effect
69
Klinefelter syndrome Genetics
XXY, nondisjunction
70
Klinefelter syndrome Sx
Extra X chromosme
Tall opposite of Turner
infertility (don't produce enough sperm to naturally fertilize egg)
lower IQ (mild)
71
Leber hereditary optic neuropathy Inheritance
mtDNA (maternally inherited)
72
Leber hereditary optic neuropathy Genetics
mtDNA mutation
73
Leber hereditary optic neuropathy Sx
Visual impairment
74
Male-limited precocious puberty Inheritance
Sex-limited AD
75
Male-limited precocious puberty Genetics
LCGR gene mutations
luteinizing hormone/chorionic gonadotropin receptor
LCGR receptor constitutively activated ->Causes excessive production of testosterone, leading to precocious puberty in males
76
Male-limited precocious puberty Sx
Early puberty in males (muscle growth, secondary sex charecteristics, short adults)
77
Monoclonic epilepsy with red-ragged fibers (MERRF) Inheritance
mtDNA (maternally inherited)
78
Monoclonic epilepsy with red-ragged fibers (MERRF) Genetics
Mitochondria tRNAlys mutation
tRNA molecule that binds L-lysine
79
Monoclonic epilepsy with red-ragged fibers (MERRF) Sx
1) Seizures
2) Muscle stiffness
3) Myopathy
4) Dementia
80
Myotonic dystrophy Inheritance
"MONTREALic"
AD
Northeastern Quebec
81
Neurofibromatosis 1 (NF1) Inheritance
AD; age-dependent penetrance and variable expressivity
82
Neurofibromatosis 1 (NF1) Genetics
NF1 gene mutation
neurofibromin helps regulate cell growth.
mutated gene causes a loss of neurofibromin, which allows cells to grow uncontrolled - therefore tumors, melanocytes in eyes (lisch nodules)
83
Neurofibromatosis 1 (NF1) Sx
Cafe au lait spots
lisch nodules (eye discoloration)
intellectual disability
tumors
84
Patau syndrome Inheritance
Sporadic, maternal age effect (can be inherited thru balanced translocations like Robertsonian)
85
Patau syndrome Genetics
Trisomy 13 (nondisjunction)
86
Patau syndrome Sx
1) Cleft lip/palate
2) rocker bottom feet
3) intellectual disability
4) polydactyly
5) fist clench
87
Polycystic kidney disease Inheritance
AD, variable expressivity
88
Polycystic kidney disease Genetics
PKD1 or PKD2 mutation (Heterogeneic)
Heterogeneic: containing more than one allele of a gene
Polycystin-2 likely functions as a channel spanning the cell membrane of kidney cells. In conjunction with polycystin-1, the channel transports positively charged atoms (ions), particularly calcium ions, into the cell
89
Polycystic kidney disease Sx
Cysts
progressive renal failure
90
Prader-Willi Inheritance
Paternal imprinting, AD
91
Prader-Willi Genetics
15q deletion or loss of paternal imprinting
92
Prader-Willi Sx
1) hyperphagia
2) obesity
3) Intellectual disability
93
Progressive hearing loss Inheritance
AD
94
Progressive hearing loss Sx
Late-onset hearing loss, fitness of 1
95
Retinitis pigmentosa Inheritance
AD AND AR (certain alleles cause AD, some cause AR- allelic heterogeneity)
96
Retinitis pigmentosa Genetics
Mutation in ORP1 gene
97
Retinitis pigmentosa Sx
Hereditary visual impairment
98
Rett syndrome Inheritance
"X linked dominant; (lethal in hemizygous males)
Question: wouldn’t this be considered X linked incomplete dominance?)"
"Rett loved his mother but was stillborn"
99
Rett syndrome Genetics
MECP2 gene (Methyl-CpG Binding Protein 2) - epigentic
MECP2 gene, which is found on the X chromosome
MECP2 needed for brain development
100
Rett syndrome Sx
Rapid onset of neurological problems
101
Smith Magenis Inheritance
Dominant
haploinsufficiency
"Guys named Smith used to be dominant - to compensate for their haplo-insufficiency"
102
Smith Magenis Genetics
RAI1 deletion; 17p11.2; de novo
103
Smith Magenis Sx
Sleep disturbances
self-injurious behaviors
104
Split/hand foot malformation Inheritance
AD, incomplete penetrance (affects about 70%)
105
Split/hand foot malformation Sx
Ectrodactyly
Greek ektroma "abortion" and daktylos "finger"
missing middle digit
106
Thanotophoric dysplasia Inheritance
AD
107
Thanotophoric dysplasia Genetics
FGFR3 mutation (same as Achon?)
Fibroblast growth factor 3 is expressed in cartilage, brain, intestine, and kidneys
108
Thanotophoric dysplasia Sx
Lethal in neonatal period (fitness of 0)
thanatophorus means "death bringing"
109
Turner syndrome Inheritance
Sporadic b/c X chromosome missing due to nondisjunction
110
Turner syndrome Genetics
Loss of X chromosome (nondisjunction)
111
Turner syndrome Sx
missing X chromosome
1) Short stature
2) shield chest (widely spaced nipples)
3) low hairline
4) intellectual disability
112
Williams Syndrome Inheritance
Dominant
haploinsufficiency
parental inversion increases recurrence risk
113
Williams Syndrome Genetics
7p11. 23 deletion
1. 5 Mb
includes ELN gene needed to make elastin
114
Williams Syndrome Sx
1) supravalvular aeortic stenosis
2) extreme friendliness
3) characteristic facial features (broad forehead, wide mouth, puffy eyelids)
115
Wolf-Hirschorn Inheritance
Dominant
haploinsufficiency
116
Wolf-Hirschorn Genetics
4p microdeletion
de novo
117
Wolf-Hirschorn Sx
1) “Greek-helmet”
2) hypotonia
3) heart defects
4) shorter life expectancy
118
X-linked epilepsy and cognitive impairment Inheritance
X linked and sex limited; affects females
119
X-linked epilepsy and cognitive impairment Genetics
Loss of surface adherin proteins on neurons from one of the X chromosomes; causes malfunction as X inactivation happens with the two different X’s (males don’t have miscommunication and compensate some other way)
120
X-linked epilepsy and cognitive impairment Sx
Developmental delay in females
male hemizygotes unaffected
121
Xeroderma pigmentosum Inheritance
AR; 20% of cases are from offspring of first cousins
122
Xeroderma pigmentosum Sx
1) Ultraviolet light sensitivity
2) freckling
3) skin cancer
