Molecular Genetics Iii

Front 1

Nucleosomes coiled around each other forms what?

Back 1

solenoid

Front 2

In interphase, DNA is coiled to what extent? (What structure is the highest level of organization in interphase)

Back 2

solenoid

Front 3

The solenoid structure condenses DNA how much from the beads-on-a-string state?

Back 3

50-fold more condensed

Front 4

One coil of a solenoid consists of what?

Back 4

5-6 nucleosomes coiled together

Front 5

During mitosis and meiosis, the DNA is condensed how much from its original state?

Back 5

5000:1

Front 6

What protein closes DNA nicks as they form in the coiling process?

Back 6

topoisomerase II

Front 7

Topoisomerase II binds to what regions of DNA?

Back 7

AT-rich

Front 8

What 2 bands form in Giemsa staining?

Back 8

dark=G bands, AT rich, less transcriptionally active
light=R bands, GC rick, more active

Front 9

ribose backbone has what kind of linkage?

Back 9

phosphodiester

Front 10

Key difference btwn DNA and RNA at molecular level

Back 10

DNA has H at 2' position, RNA has an OH

Front 11

How many hydrogen bonds form btwn C-G pairing?

Back 11

3 hydrogen bonds

Front 12

What type of bonds form when base pairs link between strands?

Back 12

hydrogen bonds

Front 13

How many hydrogen bonds form btwn A and T bases?

Back 13

2 hydrogen bonds

Front 14

Length between base pairs in a DNA strand

Back 14

0.34 nanometers

Front 15

What is a ddNTP and how is it different fom a dNTP?

Back 15

di-deoxy nucleotide triphosphate--missing the 3' OH, so nothing can be added to the chain

Front 16

How many base pairs in human genome?

Back 16

3 billion (3 x 10 9)

Front 17

How many base pairs in a megabase?

Back 17

1,000,000

Front 18

How long is 3.4 Angstroms? (distance btwn base pairs)

Back 18

0.34 nanometers

Front 19

Where is the base actually attached to the ribose backbone?

Back 19

The base (G,A,T, orC) is attached to the 1' carbon of the ribose backbone.

Front 20

Type of bond that links bases within the same DNA chain.

Back 20

phosphodiester linkage

Front 21

Chargaff's rule

Back 21

A pairs with T
G pairs with C

Front 22

What are the purines? pyrimidines?

Back 22

purines = adenine, guanine
pyrimidines=cytosine, thymine (y in name) and uracil

Front 23

Difference in purines and pyrimidines

Back 23

Purines are bigger and have 2 rings. Pyrimidines have only 1 ring.

Front 24

Describe that part of the centromere where the kinetochore microtubules bind

Back 24

171 bp repeat called alpha-satellite DNA. AT-rich. Kinetochore proteins bind here.

Front 25

What telomere sequence is conserved across all chromosomes, and even across species?

Back 25

GGGTTA

Front 26

Names of the 2 strands on newly-replicated DNA

Back 26

leading and lagging strands

Front 27

Name of pieces of lagging strand DNA that must be joined together

Back 27

Okizaki fragments

Front 28

What does helicase do?

Back 28

unwinds DNA and breaks hydrogen bonds prior to replication

Front 29

What enzyme stimulates DNA polymerase activity during replication?

Back 29

proliferating cell nuclear antigen

Front 30

What enzyme removes RNA from an RNA-DNA hybrid?

Back 30

Ribonuclease H1 (RNAse H1)

Front 31

DNA ligase connects what?

Back 31

3' hydroxyl to 5' phosphate group

Front 32

What enzyme relaxes DNA by breaking and resealing phosphodiester bonds?

Back 32

topoisomerase

Front 33

What happens at the 2nd cell cycle control point, at the G1/S border?

Back 33

site of p27 inhibition of cdk2-cyclin E

Front 34

What happens at the 3rd cell cycle control point, at the G2/M border?

Back 34

activation of cdc2-cyclin B

Front 35

What happens at the 4th cell cycle control point, at the end of mitosis?

Back 35

degradation of cyclin B

Front 36

Lagging strand primers are made of what?

Back 36

RNA

Front 37

When the strands are separeated for DNA replication, what keeps them apart?

Back 37

single-stranded DNA binding protein (replication protein A)

Front 38

Which polymerase works on the leading strand, and which on the lagging strand?

Back 38

leading =DNA polymerase delta
lagging = DNA polymerase alpha + DNA primase subunit

Front 39

When a deoxynucleotide triphosphate is added to the 3' end of the growing strand, how many phosphates are lost?

Back 39

2

Front 40

Name 3 syndromes caused by helicase malfunction.

Back 40

WRN helicase=Werner
RECQ4=Rothmund-Thompson syn.
BML helicase=Bloom

Front 41

Characteristics of Bloom syndrome

Back 41

IUGR
hypo/hyper pigmentation
butterfly telangiectasia
microcephaly, high-pitched voice
normal IQ
immunodificiency
azospermia
premature ovarian failure
increased risk for cancer

Front 42

Describe what happens at telomeres during replication?

Back 42

Telomerase binds and has an RNA template seq. that matches the telomere repeat. Shifts down repeatedly to add new 6 bp sequence.

Front 43

Name some types of splice site mutations

Back 43

cryptic splice sites (uncover old or create new)
ESE (exonic splice enhancer)-may be a silent AA change
donor/acceptor/branch site

Front 44

Sequence at the exon/intron donor site

Back 44

GU

Front 45

Sequence at the intron/exon acceptor site

Back 45

AG

Front 46

Freq. of Tay-Sachs among AJs

Back 46

1/3000 AJs

Front 47

Freq. of PKU

Back 47

1/12,000

Front 48

Enzyme missing in SCIDs

Back 48

Adenosine deaminase

Front 49

3 common Tay-Sachs mutations

Back 49

4bp insertion into exon 11
Splicing mutation in intron 12
Gly-to-Ser missense in exon 7

Front 50

4 common Gaucher mutations

Back 50

L444P missense in exon 10
IVS2+1
84GG (frameshift)
N370S missense in exon 9

Front 51

Common PKU mutations

Back 51

IVS12nt1
R158Q
R261Q
R408W

Front 52

Many common mutations for common diseases are diagnosed by what 2 techniques?

Back 52

PCR, ASOH (allele-specific oligo hybridization)

Front 53

Name some example of how dominant haploinsufficient conditions can be highly dependent on environmental factors?

Back 53

acute intermittent porphyria (heme biosynthetic pathway), familial hypercholesterolemia

Front 54

What are porphyrins? What is acute intermittent porphyria?

Back 54

Intermediate in heme biosynthesis. Anemic episodes occur due to environmental factors, need to turn up heme pathway top make more. There is a rate-limiting enzyme, porphyrins build up in blood, cause pain, photophobia, psychosis (vampire-like)

Front 55

Defective protein in familial hypercholesterolemia? Mode of inheritance?

Back 55

Low-density lipoprotein
Dominant (haploinsufficient)

Front 56

Freq. of familial hypercholesterolemia

Back 56

1/500

Front 57

Freq. of Huntington

Back 57

1/10,000

Front 58

Protein altered in myotonic dystrophy? Frequency?

Back 58

protein kinase
1/10,000

Front 59

Freq. of OI

Back 59

1/10,000

Front 60

What is highly parallel genotyping?

Back 60

Looking at many different SNPs or loci at once. Includes microarray, SNP array. Note that CGH doesn't really look at genotype, but just copy number.

Front 61

Name one condition in which Southern blooting is still used for diagnosis. Why?

Back 61

Fragile X--PCR is ineffective at long repeat expansions.

Front 62

What is an STS?

Back 62

Sequence tagged site. Unique spot in genome amplified by PCR. STS content mapping--used to find the order of sites on YAC clones, for physical mapping=a contig.

Front 63

How many base pairs are btwn 2 loci with a 1% recombination rate?

Back 63

1% recombination rate=1 centimorgan =1 million base pairs

Front 64

With regard to SNPs, what is a haplotype? How many haplotypes exist within a particular population at a locus?

Back 64

A haplotype is a group of SNP inherited as a unit. Typically 2-10 haplotypes in a population.