Genetics Pre-Midterm Flashcards
(121 cards)
1
Q
What is a phosphodiester bond?
A
Sugar-Phosphate
2
Q
Why do we 5’ cap & 3’ poly-A tail mRNA?
A
- Protection from exonucleases/increase 1/2 life
- Necessary for nuclear export
- Cap binding complex necessary for translation
3
Q
What are the 2 sites called before and after an intron?
A
- Donor site
2. Acceptor site
4
Q
What holds everything together during splicing?
A
Spliceosome
5
Q
Give an example of RNA editing
A
Apo-B-100 (liver) & Apo-B-48 (intestine)
* C –> U; a premature stop codon for the intestine isoform
6
Q
What is a Lariat structure?
A
Circular structure that forms as 5’ donor site links to an invariant part of the intron
7
Q
Humans only have 30,000 genes, but..
A
Alternative splicing can increase this in 60% of the genes
8
Q
What are enhancers and activators and transcription factors?
A
All elements that regulate/stimulate transcription; can be upstream/downstream, in an intron, etc.
9
Q
What is Chargoff’s rule?
A
A=T; G=C
Purines = Pyrimidines
10
Q
How many H bonds are A-T vs. G-C
A
A-T: 2; G-C: 3
11
Q
Who is bicyclic: purines or pyrmidines?
A
Purines
12
Q
mRNA is linear or circular; single or double stranded?
A
Linear; single-stranded
13
Q
A mutation in a donor site results in…
A
Longer gene
14
Q
The regulatory sequences of genes regulate…
A
Rate of transcription
15
Q
What does methylation do to DNA?
A
Inactivate / regulate the rate of transcription
16
Q
How many genes do humans have?
A
25-30,000
17
Q
What is the largest gene?
A
Dystrophin - 2.5Mb
18
Q
Where on a chromosome are the genes located?
A
Between the telomere and the centromere
19
Q
What are the 3 main divisions of DNA?
A
Nuclear, extragenic, mitochondrial
20
Q
What are the 2 divisions of nuclear DNA?
A
Single gene, Multigene families (Classic, superfamilies)
21
Q
What are the major divisions of multigene family genes?
A
- Classic - high degree of homology (HOX)
2. Supergene - low homology, similar fx (HLA, T cell receptor)
22
Q
The 2 major categories of extragenic DNA:
A
- Tandem repeat (satellite, mini-telomeric, hypervariable-VNTR, micro-STR)
- Interspersed (short-Sines (30-40%) & Alu elements, long-Lines (20% & reverse transcriptase))
23
Q
What part of DNA is used for fingerprinting & why?
A
STR (short tandem repeat)
STR & VNTR are polymorphic and inherited in a co-dominant fashion from mom/dad
24
Q
Mitochondiral DNA is inherited…
A
Mother (cytoplasm of oocyte)
25
Differentiate between metacentric, submetacentric and acrocentric DNA.
Meta: P=Q -- Chromo 1
Sub: P < Q -- Chromo 4
Acro: P <<< Q (satellite P) -- Chromo 13,14,15,21,22
26
A karyotype is viewed during...
Metaphase
27
What is it called when both chromosomes of a pair are derived from the same parent?
Uniparental disomy
28
In what order are chromosomes arranged?
Largest to smallest (1-21)
29
What is asymmetric X inactivation?
When more than 50% of the cells of the maternal/paternal X is active
30
What is the barr body?
The inactivated X chromosome in females
31
When does lyonization take place?
After the development of female sexual organs
32
Who regulates Lyonization?
XIST (X inactivation center); which coats the inactivated X-chromosome
33
What is an epigenetic mechanism of DNA modification?
Imprinting: Methylation of CG islands close to the promoter; results in transcriptional repression
34
Differentiate between locus and allele
Allele: homologous chromosomes (homo/hetero)
Locus: location on a chromosome
35
Huntington's disease is located ...
Chromosome 4P
36
Which are the tumor suppressor genes (with respect to the cell cycle)?
p53 & Rb
| * Between G1 & S
37
Who regulates the tumor suppressor genes?
Cyclins
38
What are the 3 major types of cells (with respect to the cell cycle)?
1. Labile -- multiply throughout life
2. Stable -- G0; can undergo division if stimulated
3. Permeant -- arrested in G0 (neuron, cardiac)
39
How does a cell in G0 get to S phase?
Through G1
40
Which stage of the cell cycle is most variable (time)?
G1
41
Cell spends maximum amount of time in Interphase or Mitosis?
Interphase
42
What is Turner Syndrome?
45, X (Non-disjunction)
43
What is Klinefelter Syndrome?
47, XXY
44
Differentiate between XYY & XXX (with respect to fertility)
XYY -- fertile
| XXX -- infertile
45
Differentiate between the beginning of gametogenesis in males/females
Males: puberty
Females: embryonic life
46
Differentiate between number of mitoses in male sex cells vs. female
Male: 30-500; female 20-30
47
Males produce ___ gametes; females produce _____
4 spermatids; 1 ovum/3 polar bodies
48
Differentiate between nondisjuction in meiosis I vs. 2
I: XY, XY, no sex chromo * 2
II: XX, YY; no sex chromo * 2
49
How many chromosomes and chromatids at the beginning of mitosis?
46 chromosomes; 92 chromatids
50
Where is the second check point in the cell cycle?
After G2
51
What is the difference between cis & trans regulatory proteins?
Cis -- same chromsome; trans -- different chromosome
52
Differentiate between (lac operon) with glucose, lactose, & glucose/lactose
Glucose: negative
Lactose: positive
Glucose+lactose: no cAMP (but also no repressor)
53
In proks, what are the components of an operon?
promoter, operator (repressor), cAMP-binding
54
What are the two different terms for the level of gene transcription in proks?
Constituitive (always on)
| Regulated (on with certain conditions)
55
How does the tryptophan operon function in proks?
In the absence of Trp, an inactive repressor is made & tryptophan is synthesized
56
What suppresses/activates the operator in the lac operon?
Normally, suppressed; but when lactose is present, allolactose binds to and suppresses the suppressor
57
Differentiate between the following mutations: non-functional repressor and a super-repressor in the lac operon.
Non-functional repressor: can't bind to the operator (Lots of transcription!)
Super-repressor: repressor has mutation and is unable to bind to allocatose, so it won't dissociate from the operator (NO transcription)
58
Transcription factors have 3 domains (euks)
1. DNA binding domain
2. Dimerization domain
3. Enhancer binding proteins
59
What are the two different types of transcriptional modification in euks?
1. Basal transcription
| 2. Enhancer transcription
60
How do transcriptional repressors work in euks?
Competition, Quenching, Blocking
61
What are hypoxia response elements?
HIF1-alpha, HIF1-beta;
Under normal conditions, HIF1-alpha is degraded by O2-dependent prolyl hydroxylase and FIH hydroxylase
In anoxia, the 2 proteins dimerize; angiogenesis, vasodilation, etc.
62
What are hormone response elements?
Up/down regulate inflammation (glucocorticoids)
63
What are MAX/MYC
MYC+MAX = gene activation
MAX alone = gene repression
MAX mutations -- pheochromocytoma
64
Describe the regulation of iron in the body.
Translational modification
| Ferritin & Transferrin
65
What are miRNA's?
Gene silencing; Drosha--long pre-miRNA's processed to mature miRNA's
DICER processes them to ssRNA & forms RISC (RNA induced silencing complex)
* Regulation gene expression by BP'ing to 3'UTR
66
What is siRNA?
Short, interfering RNA; can silence genes
67
How is Fragile X related to miRNA/siRNA?
Misprocessing, low levels of FMRP gene; RISC complex
68
What are the features of autosomal dominant disorder?
* Vertical -- doesn't skip generations
* Equal M/F
* Father --> Son
69
Define recurrence risk
Probablity that offspring will have the disorder
70
What are the characteristics of autosomal recessive?
* Horizontal inheritance; skips generations
| * M/F equal distribution
71
What are the major autosomal dominant disorders & characteristics?
```
Huntington's Disease
Myotonic dystrophy (DMPK gene)
Familial hypercholesterolemia
Margan
Achondroplasia (FGF3); cartilage-->bone
OI (alpha-1)
Neurofibromatosis (NF1)
Acute intermittent prophyria
```
72
What disorders are triplet repeat disorders?
Huntington
| Myotonic dystrophy
73
What are two examples of dominant negative mutations?
Mutant gene interferes with normal gene function (Marfan, OI)
74
What is an example of a haplo-insufficiency disorder?
Familial hypercholesterolemia; half normal levels of the gene (LDL receptors) defected
75
What are two examples of gain-of-function mutations?
Huntington/Achondroplasia; increased level of gene expression; ne functional gene producyt
76
What is the classical variable expressivity autosomal dominant mutation?
Neurofibromatosis I
77
Define incomplete penetrance
An autosomal dominant mutation skips a generation
* Pt has genotype, but not phenotype (Huntingtons)
* Can calculate the penetrance risk
78
Define variable expression
Spectrum of the disorder (different phenotypic manifestations)
I.E. Hemochromatosis, Xeroderma pigmentosum, OI, NF
79
Define Pleiotropy
Affects multiple organ systems (Marfans)
80
Define locus heterogeneity
Same phenotype, different location of the mutation, i.e. NF, BRACA1/2
81
Define allelic heterogeneity
Different mutations at the same loucs (and same phenotype, i.e. CF
82
Define new mutation
Father (increased paternal age) has germ-line mutation due to decreased recognition of DNA errors, i.e. Achondroplasia, Apert, Marfans
83
Differentiate between the 2 causes of Prader-Willi & Angelman.
Microdeletion
| Uniparental disomy
84
Describe the genetic differences between Prader-Willi & Angelman
Prader-Willi: deletion of paternal SNRPN
| Angelman: deletion of maternal UBE3A
85
Describe the 4 triplet repeat disorders
Promoter: Fragile X (CGG)
Intron: Fredrich Ataxia (GAA)
Exon: Huntington (CAG)
3' UTR: Myotonic Dystrophy (CTG)
86
There is a high/low chance of recombination for genes far apart from one another.
High; genes CLOSE to each other are considered LINKED
87
ASO probes can be used for...
CF, hemochromatosis
88
What are the limitations of PCR
- Won't ID Heterozygous/Homozygous
| - Won't ID carriers
89
What are the limits of karyotype analysis?
Unable to detect microdeletions
90
What is CGH used for?
Tumor biology
91
Describe the following terms: silent, missense, nonsense, transversion, transition
```
Silent: no change in AA code
Missense: change in protein
Nonsense: stop codon
Transition: purine for purine, etc.
Transversion: purine for pyr, etc.
```
92
PCR won't detect...
heterozygotes
93
What is the poly T tract in CF?
Associated with alternative splicing / mRNA is less stable
94
What are the 4 major types of OI?
1. Classic, blue sclera
2. Lethal, fetal
3. Progressive onset
4. No blue sclera
95
Describe MM, MZ, SZ, ZZ mutations in A1AT deficiency.
Less --> Most severe
96
Dominant negative mutation
A dysfunctional protein is incorporated into a multisubunit protein (Sickle Cell)
97
Gain of function mutation
Huntington
98
Haploinsufficiency
Familial hypercholesterolemia
99
Heteroplasmy
Mitochondiral inheritence
100
Anticipation
Triplet repeat disorders (increasing severity with newer generations
101
Overexpression of SHH
Hypertelorism
102
Differentiate between CGH and microarray cDNA
CGH: copy number variants
Microarray: gene expression
* Can both be used for tumors
103
Children with increased number of cervical ribs have a higher frequency of __________ due to ____________.
Cancer; loss of HOX gene
104
An example of a gain of function mutation is...
Achondroplasia; causes a decrease in chondrocyte differentiation and the formation of osteoblasts
105
46 XY - Swyer (Pure Gonadal Dysgenesis)
Loss of function of the SRY gene
* Female genatalia, clitoromegaly, bilateral gonads
* Increased risk of germline tumors; gonads removed
106
46 XX - Male Syndrome -- de la Chappelle syndrome
Caused by a translocation of the SRY gene
| * Typical boys and men; hypospadias, no Mullerian duct; infertile
107
AZF (azoospermia factor) mutation
Infertile men
108
FGF3 mutations (Most --> least severe)
Most severe least severe
| * Thanatophoric dysplsia (lethal) -- Saddan dysplasia -- ACH -- hypochondroplasia
109
Achondroplasia
AD; FGF3 mutation (FGFR normally inhibits chondrocyte growth)
G-C transversion at 1138: glycine arginine
* Sperm with the mutation actually have selective advantage
* A gain of function mutation
110
SHH-PTCH Gli Pathway Disorders
Holoprosencephaly: SHH or Six3 gene; single incisor; cyclopia
SLOS: 7-dehydrocholestrol reductase (in the SHH pathway); retardation
Gorlin (Nevoid basal cell carcinoma): PTCH -- early basal cell ca
Pallister Hall: Brain tumor, polydactly
Rubenstein-Taybi: CREBP gene; broad thumbs, small stature
111
Rubenstein-Taybi
CREBP gene; broad thumbs, small stature (SHH)
112
Pallister Hall
Brain tumor, polydactly (SHH)
113
Gorlin (Nevoid basal cell carcinoma)
PTCH -- early basal cell ca (SHH)
114
SLOS
7-dehydrocholestrol reductase (in the SHH pathway); retardation (SHH)
115
Holoprosencephaly
SHH or Six3 gene; single incisor; cyclopia
116
Define the 4 categories of single developmental anomolies.
Malformation: primary genetic problem (congenital heart defect)
Disruption: Short arms secondary to a decreased vascular supply (phocomelia)
Deformation: Club foot (due to low amniotic fluid)
Dysplasia: Monogenic; problems with tissue organization (FGF)
117
Define the 3 categories of multiple developmental anomolies.
Sequences: cascade effects
Syndromes: groups of anomolies
Associations: traits
118
Phocomelia
Disruption: Short arms secondary to a decreased vascular supply
119
Sonic Hedgehog protein
Tissue patterning, ventral floor plate, hair, tooth, lung, pancreas; limb patterning
120
On what chromosome is SHH?
Long arm 7
121
What are the HOX genes?
Anterior/Posterior axis; segmentation; gradient is important
| * Kids with an extra cervical rib --> higher risk of cancer
