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Flashcards in Genetics Deck (138):
1

Who are bi-cyclic: purines or pyrimidines?

Purines [A, G]

2

Phosphodiester bonds are catalyzed by which enzymes?

DNA/RNA ; DNA ligase

3

Which bases hydrogen bond 3 times vs 2? AT or GC

GC bonds 3x H

4

DNA exterior is + or - charged at physiological pH?

Negative

5

If a sample of DNA contains 35% adenine, what % of other nucleotides? What is this rule called?

35% T
15% C; 15% G
* Chargaff's rules

6

Which is more unstable: RNA or DNA

RNA [used within hours to days]; bacterial RNA used and degraded within minutes

7

Post-transcriptional modifications include:

1. Addition of 5' cap, 3' poly-A tail
2. Splicing of introns out

8

Capping of eukaryotic mRNA occurs by addition of ___________. What is the function of the cap?

7-methyl-guanosine
* Regulates export out of nucleus; translation; slows degradation

9

What are the functions of the 3' mRNA poly-A tail?

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

Splicing removes introns or exons? What is another name for a splice site? 5' donor always has; 3' acceptor has:

Introns; consensus sequence
5': GU
3' AG

11

T/F 60% of human genes are spliced in alternative ways to allow for production of different set of mRNA.

True: altered function, tissue-specific isoforms, alternative intracellular localization, membrane-bound and soluble forms

12

What is the classiscal example of mRNA editing?

Editing of apolipoprotein-B mRNA. Liver = B-100; Intestine: B-48

13

What comes first: donor or acceptor site when considering splicing of introns?

Donor followed by acceptor

14

Differentiate between RNA pol 1, 2, 3

RNA pol 1: rRNA [most abundant]
RNA pol 2: mRNA
RNA pol 3: tRNA

15

Alpha-amanatin [poison deathcap mushroom] inhibits which RNA polymerase?

RNA pol 2

16

Do promotors contact RNA pol 2 directly?

No, they use transcription factors

17

What are several examples of sequences within eukaryotic promotor regions that are recognized by RNA polymerase 2?

CAAT box; TATA box
* Basal transcription machinery also

18

T/F Enhancer sequences may be very far away from transcription start sites. What do enhancers bind to?

True; activators

19

Molecular mechanism of DMD vs. BMD

DMD: deletion/stop codon (frame-shift)
BMD: missense (in frame)

20

What is the function of dystrophin protein?

Links the actin cytoskeleton with protein complexes that are associated with sarcolemma membrane; provides cell integrity.

21

T/F PCR may not detect heterozygotes. What is a way around this?

True; multiplex ligation dependent probe amplication PCR.

22

How can females display DMD symptoms?

In the manifesting heterozygote female, there are tissues that are healthy while others are badly affected; functional mosaicism

23

The most common lethal inherited disease in Caucasians?

Cystic fibrosis

24

The principal cause of death in CF

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