Cell Molecular Bio Final Exam

Front 1

What are the major trisomies?

Back 1

16 (lethal)
13 (Patau), 18 (Edward's), 21 (down syndrome)
XXX, XXY (Klinefelter's), XYY (Supermales)

Front 2

What is the only monosomy we studied?

Back 2

Turners syndrome (XO)

Front 3

What are the three different types of chromosomes

Back 3

-metacentric
-submetacentric
-acrocentric

Front 4

Name acrocentric chromosomes?

Back 4

-13,14,15, 21, 22

Front 5

ttaggg

Back 5

telomer end sequence

Front 6

Why would you do a karotype?

Back 6

-suspected abnormality
-congenital malformation
-mental retardation
-advanced maternal age (>35)
-family history
-infertility in parents
-sex diffferentiation disorder
-multiple miscarriages

Front 7

What are types of chromosome abnoprmalities

Back 7

-inversion
-translocation
-deletion
-monosomy, trisomy, triploidy

Front 8

What type of nondisjunction is 123

Back 8

meiosis 1 nondisjunction

Front 9

uniparental isodisomy

Back 9

trisomic rescue after a meiosis II event leads to two copies of the same gene from one parent.

Front 10

Trisomic rescue

Back 10

-occurs after a nondisjunction event to kick out one of the three chromosomes

Front 11

uniparental disomy

Back 11

- trisomic rescue following a meiosis I event - i.e. 123, the 3 gets kicked out and you get 12, this is both from one parent, but they are different genes

Front 12

wolf-herchorne?

Back 12

4p deletion

Front 13

Pericentric

Back 13

-refers to a duplication or inversion that involves the centromere

Front 14

paracentric

Back 14

-referes to a duplication or and inversion that does not involve the centromere (normally on the q arm)

Front 15

Robertsonian translocation

Back 15

-normally involves acrosentric chromsomes
-the q arms of two chromosomes comes together and the p arms are lost
-this is normally fine for the subject, but results in high percentages of abnormal offspring

Front 16

Wilms tumor

Back 16

-cancer
-deletion 11p15

Front 17

Beckwith-Wiedmann

Back 17

+ 11p15

Front 18

Digeorge/VLS

Back 18

deletion
-22q11

Front 19

Cat eye

Back 19

+22q

Front 20

centromere

Back 20

- the primary constriction, looks like a pinch

Front 21

what is the p arm?

Back 21

-short arm of the chromosome
-contains lots of satellite DNA (repitions of DNA
-also is where the ribosomal RNA is kept

Front 22

giesma stain

Back 22

-staining technique
-stain hits AT rich regions
-CG regions tend to be lighter because (active chromatin turns out lightly because it is loosely packed and subjected to degradation by trypsin

Front 23

isochromosome

Back 23

you get a 2p chromosome and a 2q chromosome due to improper splitting - it splits the wrong way during mitosis

Front 24

acentric

Back 24

without a centromere
-means that you end up with monosomy; you loose the chromosome because it cannot attach to the mitotic spindle

Front 25

FISH

Back 25

-fluorescent insitu hybridization
-has a DNA probe complementary tothat region - wherever it binds it flouoresces
-for instance telomeric probes can tell you were the telomers are and if there is telomeric deletion, etc.

Front 26

SKY

Back 26

-Spectral karotyping using different dyes
-used for tumors

Front 27

what is the most common cause of down syndrome?

Back 27

-maternal meiosis I error (old mommy)

Front 28

Fragile X syndrome

Back 28

-methylation at a portion of the gene silences it
-lots of mental retardation & bad behavior

Front 29

CGH - comparative genomic hybridization

Back 29

take the sample DNA and try to hybridize it to the normal DNA, the areas that don't overlap suggest a deletion/insertion, etc...

Front 30

Prader-Will Syndrome

Back 30

- 2 copies of MATERNAL 15.11

Front 31

Angelman Syndrome

Back 31

- you have two copies of PATERNAL 15.11

Front 32

post pubertal testicular failure, small testes, azoospermia, gynecomastia, dull socially mall adjusted

Back 32

Klinefelters

Front 33

normal sex development, fertile, tall thin habitus, weak slow jail story, antisocial, explosive behavior, reduced IQ

Back 33

- supermales (XYY)

Front 34

aneuploidy

Back 34

# of chromosoems is abnormal - either yo have extra or missing chromosomes

Front 35

The four steps in Positional cloning

Back 35

1. Family studies and genetic linkage analysis - co-inheritance of the disease nad genetic markers revelals the approximate chromosomal position of the gene
2. Cloning the chromosomal region fo the disease gene - large DNA clones that encompass the disease gene's position are isolated from genomic DNA libraries
3. Transcript mapping - Candidate genes are mapped to genomic clonzes to hybridize them to mRNA transcripts from the tissues of the affected diseases
4. search for a mutation

-establish the relationship between mutations in the candidate gena dn the disease

Front 36

Retinoblastoma

Back 36

pRB - a tumor suppressor gene that is often mutated in cancer

Front 37

positional cloning

Back 37

-locating a disease causing gene on a chromosome based on its linkage to genetic markers

- the gene that is sufficient for a specific trait or disease and for which an inheritance pattern can be determinded can be located ona chromoseome and isolated by exploiting its linkage to known genetic markers

Front 38

BRCA1

Back 38

the breast cancer gene

Front 39

What are the two types of cancer genes

Back 39

1. oncogenes - promote unrestrained cell proliferation
2. tumor suppressor genes - negatively regulate cell growth, are often mutated in tumor growth

Front 40

inheritance of breast cancer gene is ...

Back 40

- inherited as a dominant genetic trait
-results in a predisoposition or susceptibility to cancer

Front 41

How does BRCA1 act as a recessive allele?

Back 41

-loss of both copies is required for cancer

Front 42

genetic marker

Back 42

-distinguish parental and maternal contributions to chromosomes to the offspring
-distinct alleles of the se polymorphisms that cna be traced through families are used as genetic markers

Front 43

What are RFLPs used for in positional cloning?

Back 43

- used with BRCA-1 to determine if you have the genetic marker that would indicated you have the disease
-result from the differences in the DNA sequecnes of a chromosome region that alter the band pattern generated by digestion with restiction enzymes

Front 44

how do we clone the chromosomal region of the disease gene?

Back 44

- genomic DNA gragments that contain the candidate gene are isolated froma l ibrary of overlapping clones that collectively encompass the chromosomal region
-library is preconstructred from NORMAL human genomic DNA
-hybridize probes to genomic libbrary to identify clones

Front 45

what kind of DNA can you use to clone the chromosomal region of the DNA?

Back 45

-normal human DNA

Front 46

How does loss of BRCA1 lead to cancer

Back 46

-BRCA1 is involved in DNA repair, loss of BRCA1 doesn't directly lead to cancer, but the cell starts to accumulate other mutations, if the mutation is in an important gene like p53, then this can lead to disregulation of the cell cycle and unregulated cancer growth

Front 47

candidate genes

Back 47

-genes that we think are the BRCA gene due to their expresison in the tissue (active), there proximity to a genetic marker, and also their location (potentially).

Front 48

transcript mapping

Back 48

-fragment s of genomic clones identified in step 2 are used as probes to ID expressed genes in the region of tissue that you're looking at

Front 49

what is the strucutre of the nuclear envelope?

Back 49

-TWO lipid bi-layers
-the outside bilayer is connecte to the ER

Front 50

what is the role of the laminins in the nucleus

Back 50

-keeps the chromatin in place (anchor)
-is a point of attahment for NP
-is important for Tx
-gives rigidity to the cell

Front 51

what holds the nucleoli in place in the nucleus

Back 51

-probably proteins
-also, fibers extending into the nucleus can hold the nucleoli in place

Front 52

how do nuclear pores regulate traffic into and out of the nucelus?

Back 52

- gives signals to the nucleus about when to turn genes on and off
-controls the movement of patricular molecules through the nucleus

Front 53

NP complex

Back 53

Nuclear pore complex
-regulates transport of molecules
-8 fold symmenry
-"basket" on the inside of the nuclear membrane

Front 54

POM121

Back 54

proteins that hold the NP in contact with the lipid bilayer

Front 55

gp210

Back 55

proteins that hold the NP in contact with the lipid bilayer

Front 56

proteins that hold the NP in contact with the lipid bilayer

Back 56

gp210
POM121

Front 57

Emerin

Back 57

-protein found near/in the NP/nuclear membrane
-defect in emerin leads to Emery-Dreifuss muscular dystropy
-Emerin-baf is required for HIV infection, but is also required for other cellular processes

Front 58

LAP2

Back 58

a protein found in the nuclear membrane required for infection with retroviruses (non-HIV)

Front 59

LBR

Back 59

a protein found in the nuclear membrane
Lamin B receptor - important for diseases
-hetoxygous LBR mutations causes Peger-Huet abnomaly in granulocytes
-homozygous LBR mutations cause Greenberg skeletal dysplasia

Front 60

Peger-Huet abnomaly

Back 60

-hetoxygous LBR mutations causes Peger-Huet abnomaly in granulocytes

Front 61

Ran-GTP/GDP

Back 61

complex is responsibe for setting up the cytoplasmic-nuclear gradient

involved in transporting cargo across the nuclear membrane through the nuclear pores.

Front 62

NLS

Back 62

- nuclear localization signal found on proteins causes the cargo to be directed to the inside of the nucleus with the help of importin and Ran-GTP.

Front 63

explain how importation works

Back 63

importin binds cargo with NLS signals, brings it thorugh the nuclear pore, Ran-GTP binds importin causing a conformational change and causing it to drop it's cargo in the inside

Front 64

explain how exporation works

Back 64

Ran-GTP binds exportin, which binds the cargo, they travel across the nuclear membrane; in the cytoplasm, hydrolsyis of the GTP causes the release of the cargo from emportin

Front 65

Ran-GTPase activating protein

Back 65

on the cytoplasmic side, helps cause the hydrolysis of GTP to GDP (with the help fo RAN BP1 (Ran binding protein)

Front 66

RanBP1

Back 66

a binding protein found on the cytoplasmic side that helps convert Ran GTP --> Ran GDP

Front 67

RCC1

Back 67

exchanges GDP for GTP. activates Ran as RanGTP

Front 68

why is nuclear regulation important?

Back 68

- to partition factors for timed interactions or regulated interactions
-speed of export can change splicing patterns and change expression of proteins

Front 69

what major molecule is responsible for the nuclear encelope coming apart during mitosis?

Back 69

-the NE is pulled apart by DYNEIN anchored ot the NE as its pulled along microtubles, it stretches until it breaks

Front 70

baf

Back 70

protein that works with emerin to bind the chromatin to the lamin

Front 71

autosomal dominant and recessive forms of EDMD

Back 71

-Disease associated with Lamin A

Front 72

-Limb-gridle muscular dystrophy

Back 72

-Disease associated with Lamin A

Front 73

-dilated cardiomyopathy

Back 73

-Disease associated with Lamin A

Front 74

dunnigan-type familial partial lipodystrophy

Back 74

-Disease associated with Lamin A

Front 75

-charcot-Marie tooth disorder type 2

Back 75

-Disease associated with Lamin A

Front 76

Hutchison-Gilford progeria syndrome

Back 76

-Disease associated with Lamin A

Front 77

atypical werner syndrome

Back 77

Disease associated with Lamin A

Front 78

purpose of the cell cycle

Back 78

to produce genetically identical daughter cells

Front 79

Which two cells cycle phases have the same amount of DNA?

Back 79

mitotic cells and cells in G2

Front 80

cells that have completed mitosis have what two options?

Back 80

-continue through G1 phase and enter s phase
-exit the cell cycle and enter Go

Front 81

restriction point

Back 81

a reugulatory point late in G1 phase - after pasing htis point, cells are committed sto entering s phase, the point of no return

Front 82

passage through the restriction point is dependent on?

Back 82

-presence of growth factors
-integrin mediated adhesion to the extracellular matrix

Front 83

what are the characteristics of a G1 phase cell?

Back 83

-prepare for entry into s phase by assembling pre-replication complexes which remain inactive until the initiation of DNA synthesis
-synthesize ribosomal RNA and proteins to support synthetic activity required for doubling of cell mass during the cell ccle

Front 84

checkpoints - what are they and what are the three types?

Back 84

-DNA damage checkpoints arrest cells in G1 phase

-purpose is to prevent a cell from replicating damaged DNA

-replication checkpoint
-S-M checkpoint
-Intra-S checkpoint

Front 85

restriction point vs. replication checkpoint

Back 85

-restriction point - there must be GF, enough nutrients & integrin mediated adhesion to get back the checkpoint - the point of noreturn for S phase entry

-replication checkpoint - in s phase cells, if there is an error at the replication fork, everything will be slowed and or halted until the damage can be repaired

Front 86

characteristics of Go arrest

Back 86

-cell has the same DNA content as a G1 phase cell
-cell has not passed the restriction poitn
-cells are not synthesizing proteins required for DNA synthesis
-cell is metabolically active
-cell type specific proteins may be expressed

Front 87

conditions that result in Go arrest include

Back 87

-absence of growth factors
-absence of amino acids (nutritional deprivation)
-cell cell contact

Front 88

What is the difference between anaphase A and anaphase B?

Back 88

anaphase A - shortening of the kinetochore MTs , movement of daughter chromosomes to poles

anaphase B - a sliding force is generated between overlap MTs from opposite poles to push the poles apart

Front 89

spindle checkpoint

Back 89

- cells will not initiate anaphase untill al the chromosomes have attached to the spindle

Front 90

G2 functions

Back 90

- get ready for mitosis
-synthesize all the machinery and proteins for M

Front 91

three different types of MTs

Back 91

astrial MTs
kinetochore MTs
overlapping MTs

Front 92

MPF

Back 92

Mphase promoting factor
-is made of CDC2/CDK1 + cyclin B
-very important !!!

Activation of CDC2/cyclin B causes the cell to go into mitosis (proteins involved : wee1 (inhib), Cdk activating kinase (activating), CDC25 phosphatase (activating)

Front 93

wee1

Back 93

-inhibits cdk1/cyclin B activity by phosphorylating the ATP binding site on the cdk1/cyclin B complex
-INHIBITS

Front 94

Cdk activating kinase

Back 94

- phosphorylates cdk1/cyclin B at another spot to activate it - won't be active until the wee1 phosphate is removed though!

Front 95

CDC25 phosphatase

Back 95

-activates cdk1/cyclin B complex
-causes cell to go into mitotic phase
-removes inhibitory phosphates added by the wee1

Front 96

ATM

Back 96

- actiavted due to ionization radiation DNA damage
-in the G1 checkpoint, phosphorylates p53, increase p53, increase p21, p21 inhibits cdk2/cyclin E
-transcription of E2F regulated genes does not occur.
-cell does not pass the restriction point

Front 97

cdk1
what cyclin does it bind
where in the cell cycle is it important?

Back 97

-binds cyclin B or (cyclin A)
-G2/M transtion
-initiates mitosis

Front 98

cdk2
what cyclin does it bind
where in the cell cycle is it important?

Back 98

-binds cyclin A for S phase progression
-binds cyclin E for G1-s transition

Front 99

cdk4
what cyclin does it bind
where in the cell cycle is it important?

Back 99

-cyclin D 1,2,3
G1 progression

Front 100

cdk6
what cyclin does it bind
where in the cell cycle is it important?

Back 100

-cyclin D 1,2,3
G1 progression

Front 101

which cyclins in associations with cdks regulate progression past the restriction point?

Back 101

-cdk4/cyclin D
-cdk2/cyclin E

Front 102

-cdk4/cyclin D
-cdk2/cyclin E

Back 102

-regulate progression past the restriciton point
-responsible for pRB phosphorylation, pRB will then dissociate E2f, which is a Tx factor that promotes cell growth

Front 103

pRB

Back 103

-tumor supressor gene involved in getting past the restriction point (G1)
-normally bound to E2f, suppresses growth

Front 104

ATR -

Back 104

UV tends to activate
-phosphorylates Chk1 - involved in phosphorylation of CDC25, prevents activation of MPF
- if activated won't get passed G2 checkpoint