Genetics Flashcards
1
Q
Who are bi-cyclic: purines or pyrimidines?
A
Purines [A, G]
2
Q
Phosphodiester bonds are catalyzed by which enzymes?
A
DNA/RNA ; DNA ligase
3
Q
Which bases hydrogen bond 3 times vs 2? AT or GC
A
GC bonds 3x H
4
Q
DNA exterior is + or - charged at physiological pH?
A
Negative
5
Q
If a sample of DNA contains 35% adenine, what % of other nucleotides? What is this rule called?
A
35% T
15% C; 15% G
* Chargaff’s rules
6
Q
Which is more unstable: RNA or DNA
A
RNA [used within hours to days]; bacterial RNA used and degraded within minutes
7
Q
Post-transcriptional modifications include:
A
- Addition of 5’ cap, 3’ poly-A tail
2. Splicing of introns out
8
Q
Capping of eukaryotic mRNA occurs by addition of ___________. What is the function of the cap?
A
7-methyl-guanosine
* Regulates export out of nucleus; translation; slows degradation
9
Q
What are the functions of the 3’ mRNA poly-A tail?
A
Increases t1/2 by protecting it from enzymatic degradation in the cytoplasm; interacts with 5’ cap which aids in export of mRNA from nucleus
10
Q
Splicing removes introns or exons? What is another name for a splice site? 5’ donor always has; 3’ acceptor has:
A
Introns; consensus sequence
5’: GU
3’ AG
11
Q
T/F 60% of human genes are spliced in alternative ways to allow for production of different set of mRNA.
A
True: altered function, tissue-specific isoforms, alternative intracellular localization, membrane-bound and soluble forms
12
Q
What is the classiscal example of mRNA editing?
A
Editing of apolipoprotein-B mRNA. Liver = B-100; Intestine: B-48
13
Q
What comes first: donor or acceptor site when considering splicing of introns?
A
Donor followed by acceptor
14
Q
Differentiate between RNA pol 1, 2, 3
A
RNA pol 1: rRNA [most abundant]
RNA pol 2: mRNA
RNA pol 3: tRNA
15
Q
Alpha-amanatin [poison deathcap mushroom] inhibits which RNA polymerase?
A
RNA pol 2
16
Q
Do promotors contact RNA pol 2 directly?
A
No, they use transcription factors
17
Q
What are several examples of sequences within eukaryotic promotor regions that are recognized by RNA polymerase 2?
A
CAAT box; TATA box
* Basal transcription machinery also
18
Q
T/F Enhancer sequences may be very far away from transcription start sites. What do enhancers bind to?
A
True; activators
19
Q
Molecular mechanism of DMD vs. BMD
A
DMD: deletion/stop codon (frame-shift)
BMD: missense (in frame)
20
Q
What is the function of dystrophin protein?
A
Links the actin cytoskeleton with protein complexes that are associated with sarcolemma membrane; provides cell integrity.
21
Q
T/F PCR may not detect heterozygotes. What is a way around this?
A
True; multiplex ligation dependent probe amplication PCR.
22
Q
How can females display DMD symptoms?
A
In the manifesting heterozygote female, there are tissues that are healthy while others are badly affected; functional mosaicism
23
Q
The most common lethal inherited disease in Caucasians?
A
Cystic fibrosis
24
Q
The principal cause of death in CF
A
End stage lung disease
25
In the chloride sweat test, what drug is used to stmulate the sweat glands?
Pilocarpine (muscarinic agonist)
26
The COL1A1 gene mutation can lead to...
OI
27
Mutations in SERPINA1 gene lead to...
A1AT (Serine protease inhibitor); loss of neutrophil elastase inhibition
28
The characteristic genetic principle demonstrated through triplet repeat expansion disorders is:
Anticipation [age of onset and severity becomes earlier in subsequent generations]
29
Repeat sequence: Huntington disease
CAG [protein coding]
30
Repeat sequence: Fragile X Syndrome
CGG
31
Repeat sequence & inheritance of: Myotonic dystrophy
CTG [AD]
32
Is there a gain of function mutation associated with Huntington disease?
Yes: polyglutamine repeat
33
The CAG repeat expansion occurs during male gametogenesis in this disorder. This is an example of meiotic drive, whereby germ cells that contain expanded repeats can have a selective advantage.
Huntington disease (in myotonic dystrophy, the CTG repeat can also lead to meiotic drive).
34
Intellectual disability, learning difficulties, elongated face, low muscle tone, flat feet and macroorchidism
Fragile X Syndrome (X-linked Dominant inheritance) CGG
35
Name the major triplet repeat expansion disorders and their triplets.
Fragile X: CGG
Huntington: CAG
MD: CTG
36
What is an example of an X-linked dominant mutation? This condition leads to methylation mediated epigenetic gene silencing
Fragile X syndrome
37
Reduced expression of the FMR1 gene
Fragile X syndrome
38
T/F Maternal anticipation results in highest triplet expansions in myotonic dystrophy
T
39
DMPK mutation results in
Myotonic dystrophy (CTG repeat)
40
Lack of muscle coordination during voluntary movments, vision impairment, scoliosis, DM, heart disorders
Freidreich ataxia [frataxin gene]; involves mitochondrial iron metabolism that leads to the formation of heterochromatin
41
Anencephaly refers to the congenital absence of the cranial vault. It is a sysraphic anomaly of neural tube closure that results from an injury to the fetus when?
During 23-26th day of gestation
42
Disfiguring neurofibromas, cafe au Lait spots, pigmented lesions of iris is due to the loss of which tumor supressor gene?
NF-1: GTPase-activating protein
43
What is one of the major complications of NF1?
Neurofibrosarcoma; meningioma, optic glioma, pheochromcytoma
44
The hallmark of this lysosomal storage disease is the presence of lipid-laden macrophages [wrinkled tissue paper] that are characteristically present in the red pulp of the spleen, liver sinusoids, lymph nodes, lungs, bone marrow.
Gaucher disease [also bone pain]
45
Anasarca in an erythroblastalis fetalis baby is 2/2
CHF
46
Which serum Ig crosses the placenta?
IgG
47
A 19-year-old man is referred to a neurologist because of failing eyesight and progressive muscle weakness. The
neurologist takes a history and finds that several of the patient's male and female relatives have similar symptoms. His
mother, her brother and sister, and two of the aunt's children are affected, but the uncle's children are not. What is the inheritance pattern?
Mitochondrial
48
Androgen insensitivity is also called
Testicular feminization
49
Gene sequence:
5'----TAAGCCAATTGG----3'
Sequence of the primer for PCR or ASO probe?
5‟----CCAATTGGCTTA----3‟
50
T/F Epigenetic modifications such as methylation regulate the rate at which transcription occurs
True
51
Give serveral examples of extragenic DNA.
Tandem repeat
* Satellite, minisatellite (telomeric, hypervariable), microsatelliite
Interspersed
52
Where is the highest gene density in DNA?
Sub-telomeric
53
Are heterochromatic and centromeric regions of DNA coding or non-coding?
Non-coding
54
Nuclear DNA can be divided into what 2 types of genes
1. Single copy: single protein
2. Multigene families
- Classic: HOX [high homology]
- Superfamilies: HLA, TCR [limited homology]
55
What % of DNA is protein coding?
<2%
56
Variable number of tandem repeats (VNTR) and short tandem repeats (STR) are inherited in what fashion?
Co-dominant [used for DNA fingerprinting]
57
Minisatellite vs. Microsatellite
Mini: Telomeric; hypervariable (6NT)
Micro: Very short sequences (2NT); short tandem repeat -- trinucleotide expansion diseases
58
Trinucleotide repeat expansion diseases are associated with which aspect of a chromosome?
Microsatellite
59
What are SINES and LINES?
Short and Long interspersed nuclear elements; some have RT activity; responsible for many of the mutations that have arisen 2/2 unequal crossover during meiosis.
60
Short arm vs. Long Arm of a chromsome
P arm: short arm
| Q arm: long arm
61
A research geneticist has identified a
tetranucleotide repeat polymorphic marker, that
is linked to an autosomal dominant disorder in a
family. This marker belongs to the class of:
Microsatellite DNA
62
T/F Genes are generally absent in the telomeres and centromere.
True
63
Differentiate between: metacentric, submetacentric, and acrocentric chromosomes.
Metacentric: p = q
Submetacentric: p shorter than q
Acrocentric: p contains very little information
64
What types of chromosomes are involved in Robertsonian translocations?
Acrocentric chromosomes: p arm contains very little genetic information
65
Karyotyping is viewed during what phase of the cell cycle?
Metaphase
66
When both the chromosomes of the pair are derived from the same parent, it is said to be called
Uniparental disomy
67
T/F X-inactivation is fixed: the same X chromosome is inactivated in all the descendants of the cell.
True
68
X-inactivation is regulated by a region on the chromosome called..
X-inactivation center: XIST
69
Methylation of _____________ bases, also called _______ islands, close to the promotor, results in transcriptional repression.
Cytosine bases; CG islands
70
The process of ___________ is similar to X-inactivation, in that the imprinted gene is methylated and transcriptionally silenced
Imprinting
71
Locus of a gene
Refers to its location on a chromosome
72
Maximum time in the cell cycle is spent in: interphase or mitosis
Interphase
73
Give examples of labile, stable and permanent cells
Labile: Skin, GIT, epithelial
Stable: Liver
Permanent: Neuron, cardiac muscle
74
The important G1-S checkpoint proteins
p53 & Rb
75
What molecules regulate the entry of cells into the various phases of the cell cycle?
Cyclins
76
What phase of the cell cycle? Nuclear envelope dissolves. Mitotic spindle forms, chromosomes start condensing and become visible; chromosomes start binding to the spindle
Prophase
77
What phase of the cell cycle? Separation of sister chromatids
Anaphase
78
What are the major events of meiosis 1 & 2?
1: Homologous chromosomes separate
2: Sister chromatids separate
79
During meiosis 1 non-disjunction...
Homologs do not separate
80
During meiosis 2 non-disjunction...
Sister chromatids do not separate
81
Male vs. Female: When does gametogenesis commence?
Male: Puberty
Female: Early embryonic life
82
In a female, oocytes are arrested in... until ovulation.
Prophase I
83
T/F There is a higher risk of maternal non-disjunction in meiosis, resulting in a higher risk of trisomy.
T
84
T/F A higher paternal age can result in the development of new dominant single gene mutations.
T
85
Locus vs. Allele
Locus: location of a gene
Allele: one of the alternative forms of a gene that occur at a locus
86
AD disorders manifest in the homo/hetero-zygous state?
Heterozygous
87
Is male-to-male inheritance seen in AD conditions?
Yes
88
Inheritance: Familial hypercholesterolemia (LDL R deficiency)
AD
89
Inheritance: Huntington disease
AD
90
Inheritance: Myotonic dystrophy
AD
91
Inheritance: Marfan syndrome
AD
92
Inheritance: OI
AD
93
Inheritance: Achondroplasia
AD
94
Inheritance: NF-1
AD
95
Inheritance: Acute intermittent porphyria
AD
96
AD mutation in the DMPK gene; most pleiotropic phenotype of all unstable 3xrepeat disorders; characterized by wasting of muscles, cataracts, heart conduction defects, endocrine defects, myotonia
Myotonic dystrophy
97
AD FGFR3 mutation
Achondroplasia
98
NF-1 is caused by different mutations in the NF-1 gene. What is this called? Locus or Allelic heterogeneity
Allelic heterogeneity
99
Horizontal inheritance: AR or AD
AR
100
In AR sibships, what proportion of non-affected siblings are carriers?
2/3
101
Inheritance: CF
AR
102
Inheritance: SCA
AR
103
Inheritance: PKU
AR
104
Inheritance: Tay Sachs
AR
105
Inheritance: Congenital deafness
AR
106
Inheritance: Hemochromatosis
AR
107
The most common mutation of the HFE gene?
C282Y mutation
108
What are several reasons for pseudo-autosomal dominant inheritance?
High carrier frequency, birth of an affected child to an affected individual, consanguinity
109
Inheritance pattern of blood types
Co-dominance
110
Is male-to-male inheritance seen in X-linked recessive disorders?
No
111
Inheritance: Duchenne & Becker muscular dystrophy
X-linked recessive
112
Inheritance: G6PD deficiency
X-linked recessive
113
Inheritance: Hemophilia A & B
X-linked recessive
114
Inheritance: Lesch-Nyhan syndrome
X-linked recessive
115
Inheritance: Red-green color blindness
X-linked recessive
116
Several possible explanations for a manifesting heterozygote in an X-linked recessive disorder
1. Skewed inactivation
2. Presence of two mutant copies (dad + mom)
3. Female with only copy of the X-chromosome
117
In X-linked dominant disorders, there is a preponderance of females compared to males.
Females; male transmits the disease to all his daughters; none of his sons are affected
118
Inheritance: Vitamin D resistant rickets
X-linked Dominant
119
Inheritance: Incontinentia pigmenti
X-linked Dominant
120
Y-linked inheritance genes are usually not passed on b/c they cause sterility. 2 Examples of Y-linked inheritance
Mutations in SRY gene; H-Y histocompatibility Ag
121
Hemochromatosis is more severe in males. This is known as:
Variable expression
122
Xeroderma pigmentosum is more severe in individuals exposed more frequently to UV radiation. This is known as:
Variable expression
123
A disease causing a mutation that affects multiple organ systems, i.e. Marfan syndrome or OI is known as
Pleiotrophic
124
Pleiotrophic disease
One mutation affects multiple organ systems: Marfan, OI
125
Mutations on chromosome 17 or 7 can lead to the manifestations of osteogenesis imperfecta. This is known as: ________. Other examples include: CMT disease, sensorineural hearing, retinitis pigmentosa
Locus heterogeneity.
126
T/F Allelic heterogeneity can lead to compound heterozygosity.
True
127
A 23 year old female is pregnant and has come for genetic
counseling. Her father (50 years) is diagnosed to have
Huntington’s disease. What is her risk of transmitting the mutant
gene to her child?
50% * 50% = 25%
128
In Huntington's disease, the disorder is generally more severe if transmitted from the father
True
129
The severity of mitochondrial disorders can vary in individuals with the disorder. This is due to the phenomenon of:
Heteroplasmy
130
Inheritance: Leber hereditary optic neuropathy
Mitochondrial
131
Inheritance: MELAS / Mitochondrial encephalopathy, lactic acidosis, stroke
Mitochondrial
132
Inheritance: MERRF / Myoclonic epilepsy with ragged red muscle fibers
Mitochondrial
133
Triplet repeat disoders: Promoter, Intron, Coding, 3' end
Promoter: Fragile X
Intron: Friedrich ataxia
Coding: Huntington
3': Myotonic dystrophy
134
Triplet repeat of FMR1 gene
Fragile X syndrome
135
Deletion of paternal 15q11-13 (absence of SNRPN) results in
Prader-Willi syndrome [obese, mental delay, underdeveloped genitalia]
* Typically, the chromosome is imprinted in the mother
136
Describe the phenomenon of trisomy rescue and its relationship to uniparental disomy
You actually have an extra copy of the chromosome
137
Deletion of maternal 15q11-13 (absence of UBE3A) results in
Angelman syndrome: Happy puppet syndrome
138
Mutations in 2 genes are additive and necessary to produce the disoder. One example of this type of digenic inheritance is...
Retinitis pigmentosa
