MCB 3rd Unit 2 Flashcards
(124 cards)
1
Q
What gene mutation results in sickle cell disease? What mutation does this cause?
A
A->T transversion in HBB beta globin encoding gene
Causes missense mutation E6V
Amino acid 6: glutamic acid (E) -> Valine (V)
2
Q
What mutation causes cystic fibrosis?
A
Delta F508
3
Q
A process used for detecting DNA bands of a specific sequence and determining their size is:
A
Southern blotting
4
Q
In Southern blotting, DNA fragments are separated based on ___ and detected by ____.
A
Size, hybridization
5
Q
What does RFLP stand for?
A
Restriction Fragment Length Polymorphism
6
Q
What process can be used to discriminate between alleles if a mutation/polymorphism changes the size of the DNA fragments?
A
Southern blotting
7
Q
What is a RFLP?
A
A polymorphism that results in a change in size of a restriction fragment. A subset of SNP’s that happen to fall within a restriction site (create or destroy)
8
Q
What are SNP’s?
A
Single-Nucleotide Polymorphisms
9
Q
Besides SNP’s, what other ways can RFLP’s be formed?
A
Chromosomal rearrangement, Deletion/insertion between two restriction sites,
Full gene deletion
10
Q
What is the mode of inheritance of hemophilia?
A
X-linked recessive
11
Q
Hemophilia A is a defect in factor ___
A
VIII (F8 gene)
12
Q
Hemophilia B is a defect in factor ___
A
IX (F9 gene)
13
Q
~40% of hemophilia A cases are caused by____ which changes the distance between restriction sites, thus changing the fragments on Southern blot.
A
Inversion d/t homologous recombination of repetitive elements near the F8 gene
14
Q
If all exons are present, can standard PCR tests detect a chromosomal inversion?
A
No
15
Q
Nail-Patella syndrom is a result of what gene mutation?
A
LMX1B
16
Q
What is the mode of inheritance of NPS?
A
Autosomal dominant
17
Q
What can be used to track a mutation in a family?
A
RFLP’s
18
Q
What is ASO hybridization?
A
Allele-Specific Oligonucleotide Hybridization
19
Q
What is ASO hybridization used for?
A
Detecting sequence variants
20
Q
How specific is ASO hybridization?
A
Can discriminate between sequences differing by a single base
21
Q
ASO hybridization can be automated, and is useful in screening for mutations that are:
A
Frequent, such as CF and beta-thalassemia
22
Q
What probe is used for ASO hybridization?
A
Oligonucleotides, one for each variant (wt and m)
23
Q
What is the mode of inheritance for DMD and BMD?
A
XR
24
Q
More residual protein function leads to more/less severe disease
A
Less
25
What is the mode of inheritance for Nail-Patella Syndrome?
AD
26
RFLP uses the principle of ____ to track mutations near a restriction site in a family
Linkage
27
The linkage tracked in an RFLP is ___ specific
Family
28
In ASO Hybridization, do we need to know the mutation?
Yes
29
Which type of diagnostic test uses dot blots?
ASO Hybridization
30
Why are only short ASO probes used?
Increase specificity, decrease mismatches which would be more stable with a long probe
31
What is the mode of inheritance for PKU
AR
32
In vitro exponential amplification of specific DNA sequences is called:
PCR
33
What is Taq
A Thermostable DNA polymerase
34
The three steps of a PCR cycle are:
Denaturing
Extension
Annealing
35
The upper limit of PCR in diagnostic labs is:
~1kb
36
A patient with sickle cell disease will have ___ reticulocytes and ___ hemoglobin
high, low
37
Southern Blot, RFLP, FISH, PCR, and CGH all rely on the principle of:
Hybridization
38
What is the inheritance pattern of sickle cell disease?
AR
39
Hemolytic anemia and swelling of the hands and feet are symptoms of:
Sickle cell disease
40
Sickle cell trait is displayed by people who are:
Heterozygotes/carriers
41
Most cases of Turner syndrome are due to a loss of a chromosome before/after fertilization (mosaicism)
after
42
A PCR based alternative to ASO hybridization
Allele-specific PCR
43
What type of PCR can be used to scan for commonly deleted exons?
Multiplex PCR
44
Define MLPA
Multiplex Ligation-dependent Probe Amplification
45
What is MLPA used for?
Detecting copy number variation
46
Give two examples of what MLPA can be used to detect
Deletions in DMD
| Duplications in Down Syndrome
47
What are four advantages of MLPA?
High-throughput
Quantitative
Fast
Cost-effective
48
What can Southern blot identify that MLPA and CGH cannot?
Balanced chromosomal rearrangements (such as F8 in hemophilia A)
49
What three sequences are necessary for a MLPA probe?
Exon complimentary
Stuffer
Standard PCR binding sites
50
In an MLPA, the number of probe ligation products is a measure of the number of:
Target sequences
51
What does "FISH" stand for?
Fluorescence In-Situ Hybridization
52
What technique(s) is/are useful in detecting small deletions?
ASO
| PCR
53
What technique(s) is/are useful in detecting medium deletions
PCR
Southern blotting
MLPA
CGH
54
What technique(s) is/are useful in detecting large deletions?
Southern blotting
MLPA
CGH
55
What technique(s) is/are useful in detecting very large deletions
FISH
56
What is the target of FISH?
Cellular chromosomal DNA
57
What is the probe used in FISH?
BACs
58
FISH is useful for detecting:
Known chromosomal rearrangements
59
What process can be used to detect unknown chromosomal rearrangements?
Spectral Karyotyping (SKY)
60
22q11 deletion syndrome, also called ___, results in "CATCH22" symptoms
DiGeorge Syndrome
61
What are the CATCH22 symptoms?
```
Cardiac defects
Abnormal facies
Thymic hypoplasia
Cleft palate
Hypocalcemia from parathyroid aplasia
22nd chromosome
```
62
What does CGH stand for?
Comparative Genome Hybridization
63
What is the gold standard for mutation identification and should identify any single base substitution?
DNA sequencing
64
Beta thalassaemia is due to what type of mutation in the beta-globin gene?
Null
65
Tandem repeats are also called:
Satellite DNA
66
Backwards slippage of a tri-nucleotide repeat causes an:
Insertion
67
Forward slippage of a tri-nucleotide repeat causes a:
deletion
68
Slippage of a non triple codon causes a:
Frameshift
69
Premature Termination Codons (PTC's) result in:
```
RNA degradation (null mutation)
*Truncated in USMLE*
```
70
The presence of ___ indicate that the ribosome is stalled at a PTC and Nonsense Mediatedd Decay machinery scans the 3 end and triggers RNA degradation
Exon Junctional Complexes (EJC's)
71
Splice sites always start at __ and end at __
GT, AG
72
The rate at which new diseases occur is:
Incidence
73
The proportion of the population affected is:
Prevalence
74
Most diseases which involve enzymes and transporters are:
Recessive
75
Most diseases which involve structural proteins and transcription factors are:
Dominant
76
Variation in a trait or clinical presentation of a disease is called:
Phenotypic (clinical) heterogeneity
77
What are the two types of genetic heterogeneity (which may cause phenotypic heterogeneity)?
Allelic and locus heterogeneity
78
What is the term describing when a variety of mutations occuring on the same gene cause the same disease?
Allelic heterogeneity
79
What is the term describing when the same mutation within a variety of genes may cause the same disease?
Locus heterogeneity
80
Gower's maneuver, calf pseudohypertrophy, and high creatine kinase are typical signs of:
DMD
81
One way to distinguis BMD from DMD at a young age is:
Ability to elevate head
82
The inheritance pattern and mutations resulting in DMD and BMD are:
X-linked recessive, dystrophin
83
A disease caused by enzyme deficiency is called an:
Enzymopathy
84
What are the two causes of disease in enzymopathies?
Substrate accumulation, product deficiency
85
What is an AR form of hyperphenylalaninemia involving a deficiency of PAH resulting in intellectual disability?
Phenylketonuria (PKU)
86
How many clinical variants of PKU exist?
3, Classic, variant, and non-PKU hyperphenylalaninemia
87
What type of heterogeneity does PKU express?
Allelic
88
In some cases of PKU, ___ supplementation is necessary to create neurotransmitters and prevent mental retardation
BH4
89
General hyperphenylalaninemia expresses what type of heterogeneity?
Locus:
PAH (PKU)
2 genes for BH4 synthesis, 2 genes for BH4 recycling
90
What is the mode of inheritance for Oculocutaneous albanism?
AR
91
What is the mechanism for oculocutaneous albanism?
OCA1 gene: tyrosinase deficiency
| OCA1B gene: milder
92
What is the mode of inheritance for maple syrup urine disease?
AR
93
What is the mechanism for maple syrup urine disease?
Deficiency of BCKDC, defective metabolism of branched chain amino acids (Val, Leu, Ile)
94
The three mechanisms of dominance are:
Haploinsufficiency
Gain of function mut.
Dominant negative mut.
95
In the mechanism ____, expression from one copy of an allele is not enough to meet physiological requirements and produce a normal phnotype
Haploinsufficiency
| Loss-of-function
96
What is the mutated transcription factor resulting in NPS?
LMX1B
97
What is defined as the probability that an individual carrying a disease-causing mutation will present with that disease?
Penetrance
| "All-or-none"
98
What is defined as the probability that individuals carrying the same mutation may present with different phenotypes
Variable expressivity
99
NPS has ___ penetrance and variable expressivity
Complete
100
FGFR3 encodes a:
TKR
101
Achondroplasia is a ___ mutation in FGFR3
G380R
102
Mutation for sickle cell?
E6V
103
Mutation for cystic fibrosis?
Delta F508
104
G380R mutation causes:
Achondroplasia
105
The G380R mutation results in a _-of-function
Gain
106
Mutation resulting in cleidocranial displasia is:
Runx2
107
What is the function of cystein that no other amino acids have?
Formation of disulfide bonds
108
When the mutant gene product interferes with the function of the normal gene product the mutation is called:
Dominant negative
109
The best example of dominant negative mutations involve ___ proteins
Structural
110
The a.a. triplet that forms collagen involves glycine and usually:
Proline and hydroxyproline/lysine
111
Hydroxylation, glycosylation, and triple helix winding of collagen occurs in the:
ER/Golgi
112
Propeptide cleavage to tropocollagen and fibril assembly of collagen occurs in the:
ECM
113
Formation/winding of collagen occurs ___ to ___.
C terminus to N terminus
114
What mutation type leads to type I OI?
Null mutation d/t haploinsufficiency
115
What mutation type leads to type II-IV OI?
Missense, Dominant negative
116
Which type of OI is the most mild? The most severe?
I, II
117
OI usually involves substitutions of which amino acid?
Glycine
118
AD polydactyly (as well as holoprosencepahly) is caused by mutations in:
SHH
119
AD polydactyly is linked to an insertion in the intron of ___ in SHH, which is an enhancer in the gene.
LMBR1
120
A mutation in Sox9 will lead to an AD disease called:
Campomelic dysplasia
121
Symptoms of campomelic dysplasia include:
Skeletal abnormalities, 46XY karyotype with female genitalia
122
Lactose intolerance (as well as campomelic dysplasia and AD polydactyly) is caused by a mutation in the ___ section of a gene
Enhancer
123
A deletion syndrome involving 7q11.23 and multiple genes including Elastin (ELN) is:
Williams, or Williams-Beuren Syndrome (WBS)
124
If different missense mutations yield distinct phenotypes, then the mutation must be ___-of-function
Gain
