Genetic Conditions Flashcards
(98 cards)
1
Q
List the ethical issues surrounding genetic testing
A
- Detection of false paternity
- Stigmatization (including survivors’ guilt)
- Loss of employment or insurance
- Psychological harm
2
Q
Diagram the relationship between the DNA molecule and chromosomes
A
Every chromosome in the body is composed of 1 DNA helix; most of the time DNA is in interphase and is just a big double helix; chromosome structure does not represent what is happening in most cells
3
Q
Chromosome disorders
A
Abnormalities in # of structure of chromosomes
- <1%
- ie. trisomy 21
4
Q
Single gene disorders
A
- (usually) affect protein function
- Mendelian inheritance (ie. autosomal dominant, and sex-linked)
5
Q
Multifactorial disorders
A
- Combination of both genes and environment
- Common; ie. CAD, cancer, dementia
- Polygenic
- Teratogenic (environmentally based)
6
Q
Mitochondrial disorders
A
- Disrupted by same mutational mechanisms as nuclear DNA
- Maternal inheritance if mutations in mitochondrial DNA; Mendelian inheritance if mitochondrial gene on nuclear DNA
- ETC genes
7
Q
Karyotyping
A
Detects alterations in #, large duplications/deletions, translocations
–>use B cell lymphocytes, add mitogen to stimulate cell division, add colchicine to stop in metaphase; stain with gemsatrypsin to digest some histones
8
Q
FISH
A
Fluorescent in situ hybridization
Detects small cytogenetic changes that are invisible on karyotype
Use probe of interest + control probe
If probe hybridizes to the sample, the DNA sequence is present
9
Q
How would you use FISH to test for WIlliams syndrome
A
add probe for elastin gene. If more green, elastin gene not in patient DNA and patient has WIlliams
10
Q
CGH
A
Comparative Genomic Hybridization
- used for deletions of extra DNA
- take patient DNA and control DNA and put in systematically ordered wells
- below 0 –> deletion
11
Q
Exome Sequencing
A
sequence coding portion of the human genome
12
Q
Mendelian single gene inheritance
A
autosomal or sex-linked, dominant or recessive
13
Q
Germline mosaicism
A
presence of more than one genetically distinct cell line in germ cells
someone can have mutation but not sow it, and then pass on mutated germ line
14
Q
What are characteristic features of Autosomal Dominant Pedigrees
A
- no skipped generations
- equal male/female affectedness
- new mutations common, many times due to germ-line mutations
- 50% of children of affected individuals also affected
- sometimes reduced penetrance or variable expressivity
15
Q
What are characteristics of autosomal recessive pedigrees
A
- skipping of generations
- possible consanguinity
- male and females equally affected
- affected individuals have 100% chance of transmitting mutated gene
- usually complete penetrance
16
Q
PKU has what type of inheritance
A
autosomal recessive
17
Q
PKU is a deficiency of ___
A
phenylalanine hydroxylase (converts Phe–> Tyr)
18
Q
Clinical features of PKU include
A
brain damage; sometimes musty odor, eczema, hypopigmentation
19
Q
What is the prognosis of someone with PKU?
A
Good if maintain diet low in protein (esp. Phe)
20
Q
What is the genetic pathogenesis of Cystic fibrosis?
A
point mutation in CFTR gene, which codes for chloride channel)
21
Q
Cystic fibrosis has what kind of inheritance?
A
Autosomal recessive
22
Q
What non-genetic test is used to test for cystic fibrosis
A
sweat chloride test
23
Q
What is a heterozygous advantage of cystic fibrosis
A
protection against diarrheal diseases (ie. Typhoid, cholera)
24
Q
What are the clinical features of Cystic Fibrosis
A
Neonatal: meconium ileus, abdominal calcifications; infancy: failure to thrive, chronic diarrhea, pneumonia;
childhood: nasal polyposis, intussusception;
adolescence & adulthood: nasal polyposis,, bronchiectasis, delayed puberty, azoospermia
25
What type of inheritance is Achondroplasia?
Autosomal dominant
26
Achondroplasia affects the _____ gene, which is a (positive/negative) regulator of bone grown
FGFR3; negative
27
Short-limbed dwarfism; rhizomelic shortening of arm and legs, macrocephaly, frontal bossing, depressed nasal ridge, and CNS complications are all features of _________
Achondroplasia
28
True or False: the majority of achondroplasia cases are due to germline mosaicisms
False; 80% are de novo mutations
29
Retinoblastoma has what type of inheritance?
autosomal dominant
has reduced penetrance
30
Neurofibromatosis type 1 has what kind of genetic inheritance?
autosomal dominant
31
Patient presents with
Cafe-au-lait macules, axillary/inguinal freckling, Neurofibromas, Lisch modules (iris hamartomaas), Bony lesions (tibial bowing). what does he likely have?
Neurofibromatosis type 1
32
Male patient presents with Dilated aortic root, ectopia lentis, skeletal changes, dural ectasia. What does he likely have?
What is the risk his new baby have of also being affected if his wife is homozygous normal?
Marfan Syndrome
50%
33
True/False: heterozygotes of sickle cell anemia have the same problems as homozygous for the mutation
False: heterozygotes have 40% HbS and are protected against Malaria
34
Reduced penetrance
not everyone who carries a mutation will express the phenotype of the mutation
35
Variable expressivity
there can be different phenotypic expressions of the same mutations
36
Consanguinity
When 2 people have blood relation to one another (& know it)
Increases risk for offspring with recessive phenotypes
37
De Novo mutations
New mutations; make inheritance patterns hard to see, 50% occurence
an explanation when kid has something but parents unaffected
38
If more than one child is affected by a genetic disorder, and both parents have been genetically tested normal, disorder likely due to ______ ______
Germline mosaicism
| presence of more than one genetically distinct cell line
39
Elevated _______ is a sign of an organic acid disorder where methylmalonyl-CoA mutase is deficent;
MMA (methylmalonic acid)
40
Elevated Methylmalonic acid is treated by
a low protein diet
41
One example of a Urea Cycle defect is _______; this will show elevated _____ in the labs
Ornithine transcarbamylase deficiency (OTC); ammonia
42
Urea cycle defects are treated with (2 things)
low protein diet and ammonia scavenger meds
43
Restricting fruits, certain vegetables, corn syrup, and table sugar will help what sort of carbohydrate disorder?
hereditary fructose intolerance
44
Lesch-Nyhan disease is a (purine/pyrimidine) disorder
purine
45
A low purine diet, allopurinol and meds for neurologic symptoms will help what disease?
Lesch-Nyhan
46
Medium chain acyl-CoA dehydrogenase is easily treated by:
avoiding fasting; rapidly treating hypoglycemia
47
Lethargy and vomiting following a fast, as well as hypoketotic hypoglycemia show indication for:
medium chain acyl-CoA dehydrogenase (MCAD) deficiency
48
Lack of biotinidase will cause biotin deficiency or toxicity?
deficiency
[supplement with biotin to treat]
49
"Gargoylism," a phenotypic expression of elevated mucopolysaccharides is present in _____ disorder;
it is treated with
Hunter syndrome
Enzyme replacement therapy
50
more than 95% of cases are due to non-familial nondisjunction
Trisomy 21
51
True of False: incidence of Down Syndrome is 1/800 live births
True
52
Describe 46, XY t(14;21) and 46, XXt(21;
4% of Down cases; due to translocation of 3rd 21 chromosome to another chromosome
phenotypically normal parents
Mother with 45,XX,t(21;21) would have 100% chance of child with Down (would pass 0 and child aborts or 2)
53
Hunter syndrome has what kind of genetic inheritance?
x-linked recessive
54
Lesch-Nyhan disease has what kind of genetic inheritance?
x-linked recessive
55
OTC deficiency has what kind of genetic inheritance?
x-linked recessive
56
T/F: Trisomy 18 (Edwards) is has 1/5-7000 incidence
True
57
Trisomy 13 (Patau) has 1/10-20,000 incidence
True
58
Name the syndrome based on the features:
- upslanting palpebral fissures
- single palmar transverse creases
- congenital heart disease (40-50%)
- hearing loss due to otitis media
- strabismus
- hypothyroidism
- moderate intellectual disablitiy
Down syndrome
59
Name the syndrome based on the features:
- low frontal hairline
- short palpebral fissures
- blunt nasal tip
- small nostrils
- small chin
- "fawn-like" ears
- high nasal bridge
Trisomy 18 (Edwards Syndrome)
60
Name the syndrome based on the features:
- holoprosencephaly
- microcephaly
- non-typical cleft
- short prominent sternum
- omphalocele
- micropenis
- "rocker-bottom" feet
- Ventricular septal defect
- cystic dysplastic kidneys
Trisomy 13
61
Name the syndrome based on the features:
- Cat-like cry
- hypotonia
- laryngeal abnormality
- growth restriction
- microcephaly
- round face with widely spaced eyes
- single palmar creaes
- moderate to severe intellectual disability
5p- syndrome (Cri du chat)
62
Name the syndrome based on the features:
- Tetralogy of Fallot
- interrupted aortic arch
- ventricular septal defect
- anomalies in branchial arch and pharyngeal pouches
- Long narrow face w/ tubular nose
- Cleft palate
- hypocalcemia
22q11.2
63
22q11.2 is due to
non-allelic homologous recombination
90% have 3Mb deletion
64
Name the syndrome based on the features:
- Wilms tumor of kidney
- Aniridia
- Genital anomalies
- Retardation of growth and development
WAGR syndrome
deletion at 11p13
65
Name the syndrome based on the features:
- cocktail personality
- hypercalcemia
- supravalvular aortic stenosis
- long philtrum
- uncanny musical abilities
- blue eyes with stellate pattern
- wide mouth
- eye puffiness
Williams syndrome
varying size deletion on chromosome 7q11
sometimes includes ELN deletion
66
Klinefelter syndrome
| karytoype & features
(47,XXY)
small firm tsticles, relatively long legs, gynecomastia, hypogenitalism, azospermia
67
Turner syndrome
(45,X)
Hand and feet edema at birth, webbed neck, lack of puberty, short stature, abnormally formed nails, coarctation of aorta, increased nuchal fold, streak gonads, infertility
68
```
Patients with (47,XXX) are infertile.
(T/F)
```
False; generally normal fertility
no phenotype
69
```
Patients with (47,XYY) are infertile.
(T/F)
```
False
70
How do you get a 46 XY female?
SRY is deleted in crossing over
71
How do you get a 46 XX male?
SRY crosses over to X in meiosis in male
72
Describe when karyotyping is useful``
- when you want to detect a large scale change
| - structural & numeric changes
73
Describe when you would use FISH
to detect small, specific cytogenetic changes
74
Which color is the control probe and the FISH probe
Control probe is green; FISH probe is red
75
When would you use CGH or microarray analysis
- when you want a broad overview with high resolution
- labeled patient & control DNA are competitively hybridized to an array, revealing gains or losses of genetic material
- Cannot detect balanced translocations
76
Why would you use FISH for a patient with Turner syndrome?
do detect any presence of Y chromosome, because will increase the risk for gonadoblastoma
77
Why do females have more varying phenotypic/disease expression for X-linked conditions compared to males?
because of the inactivation of one X chromosome (Barr bodies) in female cells
78
inactive X-chromosome
Barr body
79
Reducing X-chromosome expression to 1 of the alleles
Dosage compensation
80
differing expression of chromosomes in (somatic) cells across the body
Mosaicism
81
What type of inheritance is hemophilia
x-linked recessive
82
Reduced factor VIII is present in what condition?
Hemophilia A
83
Name the disorder based on the symptoms: normal at birth, progressive muscle weakness, pseudohypertrophy, respiratory insufficiency
Duchenne Muscular dystrophy
84
What type of inheritance does Duchenne Muscular dystrophy have?
x-linked recessive
85
What kind of inheritance is red-green-colorblindness
x-linked recessive
86
Name the disorder based on the symptoms: skin redness and blisters, progressing to thickened skin, then hyperpigmentation
seen only in females
incontinentia pigmenti
seen only in females bc x-linked dominant
87
Why is genetic variation important for evolution and speciation
important for evolution and speciation
88
p stands for _____
p2 stands for _____
q stands for _____
q2 stands for
- allele frequency of dominant allele
- percent of pop homozygous dominant
- allele frequency of recessive allele
- percent of pop homozygous recessive
89
List the assumptions required for Hardy-Weinberg Law
```
Random mating
large population
no mutations
no selection against any phenotypes
no migration
autosomal locus
```
90
What is assortative mating
when similar conditions/groups mate (ie. deafs)
91
How is inbreeding different that consanguinuity
inbreeding occurs in small geographic areas. Consanguinity occurs when a couple knows they are related
92
Explain genetic drift and the Founder Effect
when someone with/carrier of condition goes off and starts new population, allele frequency can increase in subsequent generations
93
Which autosomal recessive condition is found commonly in North European Caucasians?
Cystic fibrosis
94
What is the heterozygous advantage of the Cystic fibrosis carriers?
protection against diarrheal conditions
95
What is the heterozygous advantage of the carriers of sickle cell anemia?
protection against malaria death
96
Tay-Sachs is highly prevalent in what population?
Ashkenazi Jews
97
Which group has a higher incidence of Maple-Syrup urine disease?
Mennonites
98
Which ethnic group is more likely to have a mutation in the MPV17 gene? Why?
Navajos. Genetic drift/founder effect
