Genetics Midterm Study Guide Flashcards
(160 cards)
1
Q
What percea dentage of recognized pregnancies end in spontaneous abortion?
A
15
2
Q
What percentage of spontaneously aborted fetuses have a major chromosomal abnormality?
A
50
3
Q
what percentage of pregnancies end in real births with significant defects?
A
3-4%
4
Q
5 uses/interpretations of pedigrees
A
a. chromosomal abnormality
b. autosomal dominant condition, fully or partially penetrant, autosomal recessive
c. X linked condition, recessive or dominant
d. Mitochondrial DNA mutation
e. multifactorial condition or non-genetic cause
5
Q
allele
A
version of a gene mutation at a particular locus along a chromosome
6
Q
hemizygous
A
for X chromosome, single X allele
7
Q
variable expression of same allele
A
independent of pentrance, related to degree of expression (neurofibromatosis)
8
Q
what does 76-78del mean?
A
a deletion in coding region, nucleotides 76-78
9
Q
X in an mRNA stop sequence
A
means stop codon
10
Q
C.92+5G>A means
A
outside coding region by +5, change the G to A
11
Q
allelic heterogeneity
A
the situation in which mutations in the same gene cause the same disease possibly with different effects
same gene:same disease;different effects
12
Q
compound heterozygote
A
an individual who has two different abnormal alleles at a particular locus, one on each chromosome of a pair
different abnormal alleles
13
Q
phenotypic heterogeneity
A
different mutations in same genes cause different phenotype
mutations: same gene: different phenotypes
14
Q
locus heterogeneity
A
situation in which mutations in genes at different chromosomal loci cause the same phenotype
15
Q
penetrance
A
proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms of that disorder
16
Q
expressivity
A
degree to which a phenotype is expresed
17
Q
sex-limited
A
disease is lethal in the affected hemizygous males
18
Q
lyonization
A
x-chromosome inactivation
19
Q
autosomal dominant disease Causes (4)
A
a. gain of function
b. dominant negative
c. haplosufficiency
d. loss of heterozygosity
20
Q
haplosufficiency
A
loss of function; decrease in activity of cell
21
Q
aautosomal dominant disease pedigree reading
A
a. vertical pedigree pattern
b. each affected person has one affected parent
c. each child of affected parent has 50% of having disease
d. males and females equally affected/likely to be carriers
e. at least one affected parent (reduced penetrance and variable expressivity.
22
Q
achondroplasia type
A
autosomal dominant
23
Q
familiar hypercholesterolemia type
A
AD
24
Q
huntington’s disease type
A
AD
25
Marfan's syndrome type
AD
26
neurofibromatosis type
AD
27
achondroplasia mutation
gain of function with receptor having an overactive tyrosine kinase
28
achondroplasia mutation and occurrence of mutation
fibroblast growth factor receptor 3 gene / spermatogenesis
29
achondroplasia penetrance
complete
30
achondroplasia presentation
short stature; shortening of limps,facies with frontal bossing and midface hypoplasia, exggerated lumber lordosis, gene varum and trident hands
31
Familial hypercholesteremia three genes responsible
2 LOF, 1 GOF
32
Familiar hyeprcholesterolemia haploinsufficiency
LDL receptor binding domain of apolipoprotein B100
33
Treat familial hypercholesterolemia
with statins
34
symptoms of familial hypercholesterolemia
aortic valve stenosis
corneal arcus
tenosyvitis
35
Huntington's Disease cause
dominant negative
36
Huntington disease description
progressive disorder of motor, cognitive, and psychiatric disturbances
37
mean age of HD, survival time
35 to 44 mean age, survival time 15-18 years after onset
38
HD and CAG repeats
> 35, risk for developing HD
36-39 incompletely penetrate
>40 completely penetrate
39
anticipation
usually correlated with paternal transmission of mutated allele. phenomenon in which increasing disease severity or decreasing age of onset is observed in successive generations
40
neurofibromatosis physical expression
variable expression from cafe au lait to dermal neurofribromas
41
neurofibromatosis symptoms
learning disabilities, short stature, scoliosis, high BP and tumor prone
42
neurofibromatosis mutation
NF1 gene (regulates ras signal transduction pathway)
43
neurofibromatosis incidence
1/3500 incidence, 1/2 cases are new
44
autosomal recessive pedigree
horizontal pedigree with one or more sibs affected
parents and children of affected people not affected
nonaffected children have 2/3 chance of being a carrier and 1/3 are normal non-carriers
-look for no family history
45
albinism type
AR
46
beta thalassemia type
AR
47
cystic fibrosis type
AR
48
phenylketonuria type
AR
49
Sickle Cell Anemia
AR
50
Tay-Sachs Disease
AR
51
What kind of autosomal recessive disease is CF?
loss of function
52
CF: what can go wrong
4 things with CFTR gene; product is chloride channel
53
70 percent of CF caused by what mutation?
loss of codon Phe508
54
meconium ileus in CF
meconium becomes thickened and congested in the ileum
55
frequency of lethality of CF in children
1/3700
56
CF: what leads to infection and lung damage
abnormal mucus
57
pseudomonas aeruginosa
major pathogen in CF lung opportunistic bacteria
58
CF symptoms in pancreas
cause exocrine pancreas dysfunction, malabsorption
59
CF in liver:
hepatobiliary tract; biliary cirrhosis; gallstones
60
CF in sweat glands
elevated Cl and Na in sweat
61
CF in reproductive tract
congenital bilateral absence of vas deferens. males infertile but not sterile
62
Phenylketonuria expression depends on
protein degradation, transport and disposal of Phe, blood-brain transport and brain sensitivity
63
Phenylketonuria symptoms
mental retardation during development
64
Phenylketonuria treatment
restrict phenylalanine in diet
65
what kind of disease is Tay Sachs?
lysosomal storage disease
66
what does Tay Sachs affect
beta-hexosaminidase hydrolyzes GM2 ganglioside; accumulates ganglioside in the lysosome
67
acute infantile form of Tay Sachs disease. 4 symptoms
a. progressive weakness
b. loss of motor skills
c. decreased attentiveness
4. increased startle response
68
by when do infants die of Tay Sachs?
age four
69
juvenine and chronic, adult onset Tay Sachs is caused by
variant of hexosaminadase A deficiencies; slower progression and more variable neurologic findings
70
symptoms of juvenile and chronic Tay Sachs(4)
progressive dystonia, spinocerebellar degeneration, motor neuron disease; bipolar form of psychosis
71
Tay sachs acute infantile phenotype
three major null alleles
72
Tay sachs juvenine phenotype
later onset
survival into late childhood or adolescence
compound heterozygotes for null allele and allele that results in low enzyme activity
73
chronic and adult onset Tay Sachs phenotype
long term survival, missense alleles
74
X linked recessive diseases most common in
MALES
75
Most x linked disorders are
recessive
76
alpha thalassemia type
x linked recessive
77
color blindness type
x linked recessive
78
craniofrontasal (cellular intereference) type
x linked recessive
79
Duchene's muscular dystrophy type
x linked recessive
80
Fragile X type
x linked recessive
81
alpha thalassemia cause
locus heterogeneity
hemoglobin made of alpha2beta2, alpha on 16p, beta on 11p
mutation deleted ATRX gene located on Xq13
82
what is ATRX gene?
helicase
83
symptoms of alpha thalassemia (2)
mild jaundice; microcytic hypochromic hemolytic anemia
84
craniofrontonasal symptoms
mental and psychomotor retardatoin
| seizures
85
craniofrontonasal mutation
defect in EFNB1 gene, which encodes receptor for tyrosine kinase ligand
86
craniofrontonasal affects
mosaic female
87
Frequency of Duchene's
1/3000
88
when do DMD symptoms appear
before age 5
89
how do DMD symptoms progress?
progressive muscular weakness - proximal greater thabn distal, often with calf hypertrophy
90
Gower's maneuver
using upper body to stand up
91
Becker muscular dystrophy onset
later onset than Duckene's
92
Becker symptoms
muscle loss in hips and pelvic area, thighs and shoulders
heart can be affected
patient can develop cardiomyopathy
lungs weaken and make it difficult to breathe and clear secretions
93
Rett Syndrome type
X linked dominant
94
Hypophosphatemia type
x linked dominant
95
what is Rett syndrome?
neurodevelopmental disordfer that occurs mostly in females
96
Rett syndrome symptoms
qwringing of hands/feet
97
Rett syndrome starts
at about 6-18 months
98
in whom is Rett syndrome lethal
hemizygous males
99
What is hypophosphatemia
inability of kidneys to retain phosphate
100
what does hypophsphatemia affect?
Vitamin D metabolism
101
How is hypophosphatemia variably expressive?
more severe in males
102
symptoms of hypophosphatemia
Vitamind D resistant rickets
| short stature
103
What are Y linked diseases?
1. diseases associated with y chromosome
| have male infertility
104
hypertrichosis pinnae
hairy ears (y linked disease)
105
what is mitochondrial disease?
only passed from mother to all her children/ reduced penetrance
106
What type of disease is Leber Hereditary Optic neuropathy?
mitochondrial disease
107
What causes LHON?
one of three mutations in ND1, ND4 and ND6
108
four confounding factors of autosomal and sex linited diseases?
1. sex limited
2. cellular interference - only in heterozygotes
3. mosaicity
4. penetrance (fully penetrant to reduced to multifactorial) MS
109
what do chromosomal abnormalities cause?
infertility and recurrent miscarriages
110
50% of spontaneous abortions during first trimester are caused by
chromosomal abnormalities
111
what is most common category of genetic disease observed in prenatal analysis
chromosomal abnormalities
112
most chromosomally abnormal babies are born to
normal parents
113
homologous chromosome
individual chromosome inherited from mother or father
114
G banding
standard staining procedure to obtain a karyotype
115
acrocentric
chromosome that his its centromere chose to one end: 13, 14, 15,21, 22, Y
116
aneuploidy
abnormal number of chromosomes (normal 46)
117
polyploidy
containing more than normal multiples of chromosomes
118
nondisjunction
migration to same daughter instead of normal disjunction
119
result of nondisjunction in meiosis 1
two babies with trisomies and two with monosomny
120
result of nondisjunction in meosis 2
one monosomy, one trisomy, two normal
121
triploidy 69, XXX, XYY, YYY
common at conception but abort
| occur from multiple sperm fertilizing the ovum or chromosome segregation error
122
47, XX or XY, + 21 Down Syndrome frequency
1/8000 births
123
fertility of Downs patients
females are fertile; males are sterile
124
function of chromosome 21
controls mental functions, stature, and morphogenesis of hearts, fingers and facial musculature
125
downs characteristics
flat face, down turned mouth and widely spaced eyes
126
downs congenital malformations
heart, GI tract, dudenal stenosis/atresia, imperforate anus and hishsprung disease
127
47, XX or XY, +18 is
Edwards syndrome
128
frequency of Edwards syndrome
1/6000 births
129
characteristics of edwards syndrome
rare long term survivors and show little developmental progress
130
47, XX or XY, + 13 is
Patau syndrome
131
Patau syndrome frequency
1/10,000 births
132
symptoms of Patau
```
mental and motor deficiencies
polydactyl
heart defects
cleft palate
eye defects
```
133
45, X or 45, XO is
turner syndrome
134
characters of turner syndrome
short stature (HOX gene missing)
sexual infantilism and ovarian dysgenesis
puffy feet
redundant skin at back of neck
135
congenital defects of turner syndrome
heart and kidney
136
turner syndrome histology
cortical stroma without germ cells - no follicles
137
cause of Turner syndrome
60-80% due to absence of fraternal X/Y chromosome due to loss during meiosis in the father. Loss during mitosis in embryo causes mosaic 45,X/46, XX
138
SHOX gene
at tips of X and Y chromosomes. encodes transcription factor in embryonic limbs
139
can turner syndrome be diagnosed at birth?
yes
140
47, XXY is
klinefelter syndrome
141
How many barr bodies in klinefelter syndrome?
1
142
klinefelter syndrome frequency
1/500 - 1/1000
143
characteristics of Klinefelter syndrome
hypogonadism, and taller and longer arms
low testosterone
reduced muscle mass and IQ
gynecomastia
144
Are klinefelter syndrome patients fertile?
most are sterile due to atrophy of seminiferous tubules
145
what are 48, XXXY and 49,XXXXY
klinefelter syndrome
146
47,XXX- is
trisomy X
147
trisomy X frequency
1/1000 felames
148
what causes trisomy X
90% due to nondisjunction in mother; increases with age
149
Is trisomy x usually benign?
yes
150
characteristics of trisomy X
sterility
menstrual irregularities
mild retardation
151
What increases severity of trisomy X
increasing Xs (48, XXX or 49, XXX)
152
47, XYY is
47, XYY syndrome
153
47, XYY syndrome characteristics
taller
IQ reduction by 10-15 points
high in prison
154
in 47, XYY, what is xtra Y related to?
ADD and learning issues
155
46 XX male or 46 XY female caused by
error in cross over between X and Y chromosome exchange in the Sry gene
x chromosome has larger portion ochromosome with SRY
Y chromosome is missing SRY gene
156
XX male, XY female gametes
have no gametes
157
SRY gene
on y chromosome
| sex determining gene
158
when does SRY activate
SRY starts expression after week 6. gonad formation week 7.
159
what does SRY activate?
SOX9 gene (for skeletal and testis formation)
160
Where is SHOX gene
tip of X and Y chromosome in pseudoautosomal region
