Genetics

Front 1

4 principles for Genomic Medicine to be effective

Back 1

1. Accurate Diagnosis
2. Education and informed consent
3. Share decision making
4. Support

Front 2

Genetic risks can be based on either a particular ________ or upon ________ of a given disorder.

Back 2

genetic model (modular risk), observed frequency (empiric risk)

Front 3

Used in recurrence risk counseling for Mendelian traits:

Back 3

Modular Risks (Genetic Model)

Front 4

Used in determining recurrence risks for multifactorial disorders and chromosomal abnormalities:

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Empiric Risk (Observed Frequency)

Front 5

Where a diploid cell generates an identical diploid cells:

Back 5

Mitosis

Front 6

Occurs during gamete formation:

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Meoisis

Front 7

A diplod progenitor cell generates four haploid gametes:

Back 7

Meoisis

Front 8

Recombination is frequent:

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Meoisis

Front 9

Rod shaped strucutres of condensed DNA that come in pairs, which gcontain genetic material:

Back 9

Chromosomes

Front 10

Humanes have __, or __ pairs
__ pairs of autosomes (non-sex);
__ pair of sex chromosomes

Back 10

Humanes have 46, or 23 pairs
22 pairs of autosomes (non-sex);
1 pair of sex chromosomes

Front 11

_______________ chromosomes are a pair inherited from the different parents, and generally carry the same genes in the same order, but do not have the same DNA sequence.

Back 11

Homologous

Front 12

Network of filaments overall responsible for separating the chromosomes during cell division:

Back 12

Spindle apparatus

Front 13

Two identical strands of a replciated chromosome, joined by the centromere

Back 13

sister chromatids

Front 14

Located in the centrosomes and produces the mictrotubules

Back 14

centrioles

Front 15

organelle that is the primary microtubular organizing center that splits and forms the spindle apparatus

Back 15

centrosomes or MTOC (microtubules organizing center)

Front 16

constriction on chromosome at which the sister chromatids are held together

Back 16

centromere

Front 17

protein structure on the centromere to which the springle fibers are attached

Back 17

kinetochore

Front 18

radiate in all directions and aid in spindle orientation immediately before mitosis

Back 18

astral microtubules

Front 19

overlap in midline and responisble for pusing the poles of the spindle apparatus apart

Back 19

polar microtubules

Front 20

responsible for pulling the sister chromatids of each chromosome apart

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kinetochore microtubules

Front 21

If a cell is destined to divide again, it enters ___ ; NO DNA SYNTHESIS

Back 21

G1

Front 22

Hours of G1?

Back 22

10-12 hourse

Front 23

If a cell is not destined to divide, it enters __ phase

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G0

Front 24

Stage of DNA Synthesis

Back 24

S Phase

Front 25

In __ phase, each chromosome consists of two sister chromatids. __ is ended by mitosis, which begins when chromosomes begin to condense and ebcome visible under the microscope.

Back 25

G2

Front 26

____________ is the period between one mitosis and the next. The chromosomes are extremely elongated, uncondensed strants

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Interphase

Front 27

Phase that starts with chromosomal condensation, a progressive selective DNA packaging of the DNA along the protien scaffolding.

Back 27

Prophase

Front 28

Phase in that, as condensation occurs, highly and less condensed regions develop (correspond with the light and dark banding patterns).

Back 28

Prophase

Front 29

Each chromosome contains two strands of DNA (sister chromatids) connected together at a centromere. What phase?

Back 29

Prophase

Front 30

Centrioles divide and migrates toward opposite poles of the cell. What phase

Back 30

Prophase

Front 31

Phase that starts abruptly with disruption of nuclear envelope, which breaks into membrane vesicles.

Back 31

Prometaphase

Front 32

Phase in which, spindle microtubules enter the nuclear region

Back 32

Prometaphase

Front 33

Phase where kinetochores mature and attach to the kinetochore microtubules.

Back 33

Prometaphase

Front 34

The remaining mictrotubules are polar microtubules and those outside are astral microtubules. What phase?

Back 34

Prometaphase

Front 35

Phase where the nuclear membran disappears, chromosomes become maximally condensed and easily visible on light microscopy.

Back 35

Metaphase

Front 36

Kinetochore microtubules align chromsomes at equatorial plate midway between the poles of the cell. What phase?

Back 36

Metaphase

Front 37

In this phase, polar microtubules begin to associate in preparation for anaphase.

Back 37

Metaphase

Front 38

In this phase, centromeres abruptly separate.

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Anaphase

Front 39

Each sister chromatid is pulled to its opposite pole by kinetochore microtubules in this phase:

Back 39

Anaphase

Front 40

The kinetochore microtubules shorten and draw the chromosomes towards the spindle poles in this phase:

Back 40

Anaphase

Front 41

The polar microtubules elongate forcing the two poles of the spindle father apart in this phase:

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Anaphase

Front 42

The arrivale of the chromosomes at the spindle poles marks the end of ___phase.

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Anaphase

Front 43

In this phase, the spindle apparatuse begins to dissociate:

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Telophase

Front 44

Polar microtubules elongate, further separating the two poles in this phase.

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Telophase

Front 45

A nuclear envelope begins to form about aggregated chromosomes at each pole in this phase:

Back 45

Telophase

Front 46

In this phase, chromosomes begin to decondense and the nucleoli reappear:

Back 46

Telophase

Front 47

Mitosis is at an end and cell enters cytokinesis (cell division) in this phase:

Back 47

Telophase

Front 48

___________ occurs by cleavage, which began during anaphase.

Back 48

Cytokinesis

Front 49

A cleavage furrow develops around the midsection of the cell:

Back 49

Cytokinesis

Front 50

__________ has four stages analogous to mitosis: prophase, metaphase, anaphase, and telophase.

Back 50

Meosis I

Front 51

Prophase in ________ is much more complex and may span (in the oocyte) for 40 years or more

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Meosis I

Front 52

At the end of _______, chiasmata are observed - position where chromsomes touch and crossing over has occurred between chromatis of homologous chromosomes.

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Prophase I

Front 53

Positions where chromosomes touch and crossing over has occured between chromatids of homologous chromosomes are called: ______

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Chiasmata

Front 54

A pair of homologues held together by chiasmata is called ____ .

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Bivalent

Front 55

The _____ gene lies near the pseudoatosomal boundary on the Y chromosome and is responsible for male sex determination.

Back 55

SRY gene (sex-determining region)

Front 56

___phase of the primary oocyte starts during fetal life, ramining in "suspended" phase until the oocyte matures and is ovulated

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Prophase

Front 57

It is well known that the origin of the additional chromosome 21 in most cases of _________ is maternal. (Disease)

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Down syndrome

Front 58

The failure of two chromosomes in a pair to disjoin during anaphase of cell division is called _______

Back 58

Nondisjunction

Front 59

Steps in preparing a karyotype:

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1.) Phytohemgluttinin (PHA) is added to agglutinate RBC's and stimulate lymphocytes to divide.
2.) Cell division is blocked at metaphase with inhibitor of spindle formation (Colchicine), which leads to breakdown of nuclear membrane.
3.) Condensation of chromosomes occurs, but chromosomes do not organize along metaphase plate.
4.) The cells are lysed in hypotonic saline.
5.) The cells are droppsed onto a slide, stained and photographed under a microscope.
Each normal metaphase chromosome can be seen as two chromatids held together at the centromere.

Front 60

_________ nondisjunction would lead to mosaicism.

Back 60

Mitotic

Front 61

If nondisjunction occurs during Meosis I, the gametes formed will contain:

Back 61

both parental chromosomes (maternal and parental) that failed to separate, or neither.

Front 62

If nondisjunction occurs during Meosis II, gametes will contain:

Back 62

two copies of on parental chromosomes (either maternal or paternal), or neither.

Front 63

46, XX, del (5)(p15.3)
What disease?

Back 63

Cri du chat syndrome
deletion of band 5p15.3

Front 64

47, XY, +21
Sex? Disease? Loss or gain of material?

Back 64

A boy with trisomy 21.
Gain of material.

Front 65

46,XX / 45, X
Disease? Inheritance?

Back 65

A mosaic case of Turner's syndrome.

Front 66

45,X - Non-disjunction of sex chrom. In Anaphase I, Monosomy (45,X)
Disease?

Back 66

Turner's Syndrome (XO)

Front 67

XXY - Nondisjxn of sex chrom. In Anaphase I, Trisomy (47, XXY)
1:500 males
Disease?

Back 67

Klinefelter's Syndrome

Front 68

Trisomy 13
0.2:1000 births
Disease?

Back 68

Patau's Syndrome

Front 69

Primary amenorrhea, webbed neck, short, coarctation of Aort
Disease?

Back 69

Turner's Syndrome (XO)

Front 70

del22q
Disease?

Back 70

Velocardiofacial Syndrome

Front 71

Patients with Down syndrome are prone to develop health problems as they approach an age of about 50 years. The most important of these old-age problems is

A) Liver failure
B) Leukemia
C) Kidney failure
D) Parkinson’s disease
E) Alzheimer’s dementia

Back 71

E) Alzheimer's Dementia

Front 72

3-4 % have translocation (some partial reciprocal, most Robertsonian; 46XY,rob(14;21)),+21
Disease?

Back 72

Downs Syndrome

Front 73

Hypertonicity, clenched fingers
Prominent occiput
Low-set, malformed ears
Small chin
Rocker-bottom feet
Heart defects
Failure to thrive
Profound mental retardation
Disease?

Back 73

Edwards Syndrome

Front 74

(47XX/XY,+18)
Disease?

Back 74

Edward's Syndrome

Front 75

Shore stature, broad (shield chest), webbed neck and low hair line. Affected females have primary amenorrhea due to lack of estrogen secretion by underdeveloped ("streak") ovaries.
Disease?

Back 75

Turner's Syndrome

Front 76

5p-, deletion of the long arm of chromosome 5
Disease?
Inheritance?

Back 76

Cri du Chat Syndrome
Chromosomal

Front 77

Loss of heterozygosity in genomic locations close to the site of the mutation is observed in the malignant tumors of many patients with inherited cancer susceptibility. The most likely cause for loss of heterozygosity in these patients is:

A. A missense mutation in the intact copy of the affected tumor suppressor gene
B. A nonsense mutation in the intact copy of the affected tumor suppressor gene
C. A frameshift mutation in the intact copy of the tumor suppressor gene
D. Amplification of the affected oncogene
E. Mitotic crossing-over of the affected chromosome

Back 77

E is correct. Loss of heterozygosity can also be caused by large deletions, mitotic non-disjunction, or gene conversion. But mitotic crossing-over seems to be the most common mechanism.

Front 78

Loss of heterozygosity in genomic locations close to the site of the mutation is observed in the malignant tumors of many patients with inherited cancer susceptibility. The most likely cause for loss of heterozygosity in these patients is:

A. A missense mutation in the intact copy of the affected tumor suppressor gene
B. A nonsense mutation in the intact copy of the affected tumor suppressor gene
C. A frameshift mutation in the intact copy of the tumor suppressor gene
D. Amplification of the affected oncogene
E. Mitotic crossing-over of the affected chromosome

Back 78

E is correct. Loss of heterozygosity can also be caused by large deletions, mitotic non-disjunction, or gene conversion. But mitotic crossing-over seems to be the most common mechanism.

Front 79

Cause of aneuploidy?

Back 79

nondisjunction during meiosis

Front 80

Cause of mosaicism?

Back 80

one chromosome gets turned off. (random X chromosome gets turned off at 2-10,000 cell stage)

Front 81

Profound mental retardation, heart defects, small chin, malformed ears, rocker-bottom feet, clenched fingers, die within a year.
Disease?

Back 81

Edward’s syndrome (18 trisomy)

Front 82

Profound mental retardation, 88% heart defects, sloping forehead, low-set malformed ears, eye abnormalities, cleft lip and palate, polydactyly, deafness, die within first year.

Back 82

Patau syndrome (13 trisomy)

Front 83

Purified DNA clone probe (large piece of DNA). Uses fluorescent dye on single strand probe, allow annealation to denatured DNA. A part of chromosome lights up.
Name of method?

Back 83

FISH analysis (Fluorescence in situ hybridization)

Front 84

Highly variable, defect in aortic area, 3rd, 4th brachial arch underdeveloped (give rise to neural crest cells that migrate), hypoparathyroid, hypocalcemia, reduced immune function, increased psychiatric diseases (Schizophrenia), palate abnormalities, lower IQ
Disease?

Back 84

DiGeorge/ Catch-22/ VeloCardioFacial Syndrome

Front 85

A single-base substitution converts an A in the coding strand of a gene into a T, thereby changing the codon AAG, which codes for lysine, into UAG. This mutation is characterized as:

A. Indel
B. Missense mutation
C. Frameshift mutation
D. Silent mutation
E. Nonsense mutation

Back 85

E is correct. A nonsense mutation is defined as a mutation that changes an amino acid coding codon into a stop codon, thereby causing the synthesis of a truncated protein.

Front 86

A single Barr body is typical for

A) a triple-X superfemale
B) an infertile patient with Klinefelter syndrome
C) A death row inmate with XYY “murderer chromosome”
D) a phenotypic female with androgen insensitivity syndrome (“testicular feminization”)
E) a female with Turner syndrome

Back 86

B

Front 87

Which of the following is the most common cause of Down syndrome?

A) Illegitimate crossing-over in maternal or paternal meiosis 1
B) Non-disjunction in maternal meiosis 1
C) Non-disjunction in maternal meiosis 2
D) Chromosome breakage near the centromere
E) Formation of a triploid gamete

Back 87

B

Front 88

Mental retardation, microphthalmia, microcephaly, cleft lip and palate, polydactyly, rocker-bottom feet, congenital heart disease. Death by 1 year old.

Back 88

Patau’s Syndrome
(Trisomy 13)

Front 89

Mental retardation, micrognathia, rocker-bottom feet, con-genital heart disease, flexion of fingers (clinched hands). Death by 1 year old.

Back 89

Edward’s Syndrome
(Trisomy 18)

Front 90

Method used commonly in molecular diagnostics to detect large trinueclotide repeat expansions like those seen in fragile X syndrome (affected individuals), myotonic dystrophy, and juvenile (early onsite) Huntington disease.

Back 90

Souther Blot

Front 91

The tendency of some genetic diseases to get worse in successive generations. This is caused by an unstable “premutation” that is prone to develop into a more serious defect. The cases known so far are expansions of triplet repeats that become amplified progressively once they have reached a certain length.

Back 91

Anticipation

Front 92

Some bases in the DNA can undergo spontaneous tautomeric shifts, forming chemical structures with unusual base-pairing properties. At what point is the presence of a tautomeric shift most likely to cause a mutation?

A. During addition of a phosphate to a ribonucleoside
B. During a visit to the beach with a lot of sunlight
C. In a person suffering from Cockayne syndrome
D. During addition of bases to a replicating DNA strand
E. During the excision part of nucleotide excision repair

Back 92

D is correct, because the complementary base is selected at this point

Front 93

A girl had developed repeated attacks of pneumonia almost immediately after birth. A blood test taken 3 weeks after birth showed a blood hemoglobin concentration of 4.5% (normal at that age: 15-19%). This could possibly be a serious case of:

A. Sickle cell disease or α-thalassemia but not β-thalassemia
B. α-thalassemia but not sickle cell disease or β-thalassemia
C. Sickle cell disease or β-thalassemia but not α-thalassemia
D. Sickle cell disease but not α-thalassemia or β-thalassemia
E. α-thalassemia or β-thalassemia but not sickle cell disease

Back 93

B is correct. Only α-chain defects are expressed shortly after birth, but β-chains become important only within several months after birth, when they replace the gamma-chains.

Front 94

Many oncogenic mutations change the rate at which cellular genes are expressed. All of the following methods can be used to compare the gene expression profiles of cancer cells with those of the normal cells from which they are derived, except:

A. Southern blotting
B. Western blotting
C. A DNA microarray
D. Northern blotting
E. An immunological test that uses antibodies in order to detect proteins

Back 94

A is correct. Southern blotting is used only for DNA, whereas the other methods are used for RNA or proteins.

Front 95

Neurodegenerative disorder
Progressive disability
Personality change
Memory loss
“Chorea” motor problems.
Early onset when disease is inherited paternally
37 years is usual age of onset but 100% penetrance by 80 years old
Disease?

Back 95

Huntingtons Disease

Front 96

1:10,000
25% representing new mutations
Highly variable expressivity
Mutation in Fibrillin gene results in Stretchy Connective Tissue.
Disease?

Back 96

Marfan
Syndrome

Front 97

CAG trinucleotide repeat expansion in genes coding for glutamines 36-21 repeats
Disease?

Back 97

Huntington's Disease

Front 98

Pancreatic Insufficiency
Chronic lung disease
Male infertility
Mecarium ileus in 10% of neonates
Symptoms of ______ ?

Back 98

Cystic Fibrosis

Front 99

Deletion mutations in the alpha 1 and alpha 2 chains in collagen type I
pt.mutation replacing glycine leading to over hydorxylation and improper triple helix formation.
Disease?

Back 99

Osteogensis Imperfecta

Front 100

CTG repeats @3' UTR on Chromosome 19
Disease?

Back 100

Myotonic Dystrophy

Front 101

Used to sequence DNA
Technique?

Back 101

Southern Blot

Front 102

Multiple phenotypic effects of a single gene. The term is particularly used if the effects are not obviously related.

Back 102

Pleiotrophy

Front 103

Point mutation of the FGFR3 gene causes ______

Back 103

Achondroplasia

Front 104

Achondroplasia is a gain or loss of function mutation? Why?

Back 104

Gain of function since the abnormal gene product results in abnormal bone growth.

Front 105

What gene is mutated in achondroplasia?
Base substitution? Location?

Back 105

- Fibroblast Growth Factor Receptor 3 gene(FGFR3)
G --> A @ 1138

Front 106

What kind of inheritance does achondroplasia exhibit?

Back 106

Auto Dominant

Front 107

- Abnormal cartilage and fibrous CT formation
- Bones, ligaments, tendons, and muscles affected:
- Short stature
- Disproportional short arms and legs
- Large head
- Frontal bossing w/Mid face hypoplasia
- Hypotonia in infancy
- Delayed motor development
Disease?

Back 107

Achondroplasia

Front 108

Arachnodactyly, ectopic lentis, aortic aneurysm
Tall stature, extra long limbs, hyper joint mobility

Back 108

Triad: Arachnodactyly, ectopic lentis, aortic aneurysm
Marfan Syndrome

Front 109

What 2 cardiovascular problems often occur in Marfan syndrome?

Back 109

1.) Defective mitral valve (prolapsed)
2.) Defective aorta (aneurysm)

Front 110

Mutation of FBN1 @ 15q21.1 causes what disease?

Back 110

Marfan Syndrome

Front 111

How are the mutations causing Marfan Syndrome described? Why are they called this?

Back 111

Dominant negative mutations
Dominant inheritance --> negative effects

Front 112

Triplet repeat expansions (CGG) in Fragile X syndrome interferes by?
A) Decreasing mRNA synthesis
B) Increasing mRNA synthesis
C) Creating splicing defect
D) Gain of function mutation
E) Dominant negative mutation

Back 112

A) Decreasing mRNA synthesis

Front 113

Corresponds to progressively early onset and increased severity in successive generations
Mild symptoms to severe symptoms in successive generations
Mechanism = STEPWISE expansion of unstable trinucleotide repeats over generations
This is called?

Back 113

Anticipation

Front 114

Mutation in Huntington's Disease?

Back 114

CAG trinucleotide expansion.
Symptoms present after > 38 CAG repeats

Front 115

X-linked disorder that is characterized by joint and muscle hemmorrhage. Easy bruising and prolonged bleeding is characteristic. There is a deficiency of Factor VIII.
Disease?

Back 115

Hemophilia A

Front 116

Treatment for Hemophilia A?

Back 116

Desmopressin
Good for mild cases of Hemophilia A to increase endogenous production of Factor VIII

Front 117

Deletion in Dystrophin gene causes?

Back 117

Duchenne's and Becker Muscular Dystrophy

Front 118

Duchenne Muscular Dystophy is inherited by _____.

Back 118

X-linked Recessive

Front 119

Patient is present with muscle wasting, pseudohypertrophy of calves, high levels of CK in the blood.
What disease?

Back 119

Duchenne or Becker's Muscular Dystrophy

Front 120

Affected males with normal mates have no affected soncs, but all daughters are affected.
Both male and female children have a 50% risk of inheriting the phenotype.
Type of Inheritance?

Back 120

X-linked Dominant

Front 121

This disorder only affects only girls, who develop severe, progressive mental impairment often with autism, loss of purposeful use of the hands, spastic paraparesis, ataxia, 'acquired' microcephaly, and a pecular involuntary hand wringing.
Disease?

Back 121

Rett Syndrome

Front 122

Amplification of CGG in FMR1 of X chromosome (female meiosis) causes ________

Back 122

Fragile X Syndrome

Front 123

CFTR gene on chromosome 7, 3 Bp deletion
Disease?

Back 123

Cystic Fibrosis

Front 124

Inheritance pattern of Cystic Fibrosis?

Back 124

Autosomal Recessive

Front 125

Different mutations at the same locus (or gene) cause the same disorder is called ___________ .

Back 125

Allelic Heterogeneity

Front 126

A single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci is called ______.

Back 126

Locus Heterogeneity

Front 127

_________ is when some individuals fail to express the trait, even though they carry the allele.

Back 127

Nonpenetrance or Incomplete Penetrance

Front 128

__________ are prevalent in regions of the world where malaria is endemic.

Back 128

Thalassemias

Front 129

A mutation in the gene coding for phenylalanine hydroxylase, which lieads to deficient enzyme activitiy causes ______.

Back 129

Phenylketonuria (PKU)

Front 130

Empiric Risk of Maternal Robertsonian Translocation of (13;14)

Back 130

1%

Front 131

Empiric Risk of Paternal Robertsonian Translocation of (13;14)

Back 131

1%

Front 132

Empiric Risk of Maternal Robertsonian Translocation of (14;21)

Back 132

10-12%

Front 133

Empiric Risk of Paternal Robertsonian Translocation of (14;21)

Back 133

1-5%

Front 134

Empiric Risk of Maternal Robertsonian Translocation of (21;21)

Back 134

100%

Front 135

Empiric Risk of Paternal Robertsonian Translocation of (21;21)

Back 135

100%

Front 136

Empiric Risk of Maternal Robertsonian Translocation of (13;13)

Back 136

100%

Front 137

Empiric Risk of Paternal Robertsonian Translocation of (13;13)

Back 137

100%