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BIOL 439 > Midterm 1 > Flashcards

Midterm 1 Flashcards

1
Q

epidemiology seeks to explain….

A

the distribution of disease

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2
Q

what question does epidemiology seek to answer?

A

why did this patient develop this disease at this time and why are different individuals at different risks for different diseases?

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3
Q

what did ignaz semelweiss observe in vienna’s general hospital 1840?

A

Expectant mothers exposed to the ward with doctors, had a higher incidence of ‘Childbed fever’ than the other ward, with midwives only.
-> Childbed fever was typically fatal for the mother.

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4
Q

what did ignaz semelweiss conclude from his observation?

A

discovered that childbed fever in the first maternity ward (10% of mothers) could be reduced to the same levels as the second ward (2%), if the doctors and medical students washed their hands.

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5
Q

what is john snow known for accomplishing in 1854?

A

identified the source of a cholera outbreak in london and effectively neutralized it

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6
Q

what did john snow determine was the source of the cholera outbreak?

A

he determined that cholera incidence was highest among those exposed to the Broad Street pump

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7
Q

in _____ a _____ outbreak in London killed ___ people in ____ days.

A

1854, cholera, 500, 10

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8
Q

what was causing the cholera outbreak?

A

a sink drain inside broad st pump leaked into the public well. contaminated bed sheets that were washed at that address were likely the source of infection

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9
Q

what epidemiological tool was used by john snow?

A

the spot map

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10
Q

what do the black bars on the spot map represent?

A

reflect the # of people that died at that specific address

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11
Q

what does the line drawn around the spot map mean?

A

line drawn around everyone who used the broad st pump

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12
Q

what is another example of using a spot map?

A

haiti mapping the cholera outbreak after the earthquake -> UN workers brought cholera over and created outbreak

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13
Q

the odds of an event…

A

is the probability that it will happen divided by the probability that it will not

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14
Q

how are the odds of exposure in cases (diseased) calculated?

A

divide # of cases who were exposed by the # of cases who werent exposed

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15
Q

how are the odds of exposure in controls (healthy) calculated?

A

divide # of controls who were exposed by # of controls who werent exposed

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16
Q

how can the odds ratio be calculated from the odds of exposure in cases and the odds of exposure in controls?

A

divide the odds of exposure cases by the odds of exposure in controls

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17
Q

what is the significance of an odds ratios > 1.0?

A

the cases (dz’d) were likely to have been exposed

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18
Q

what is the significance of an odds ratio = 1.0?

A

the cases are no more likely to have been exposed than the controls

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19
Q

what is the significance of an odds ratio < 1.0?

A

the cases were less likely to have been exposed than the controls were

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20
Q

what is an example of an exposure and a disease condition which would likely give odds ratio > 1.0?

A

CF patients are more likely to have a CFTR mutation than the average control person

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21
Q

what is an example of an exposure and disease condition which would give odds ratio = 1.0?

A

parkinsons dz patients are no more likely to be named michael j fox than the average person

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22
Q

what is example of an exposure and disese condition which would give odds ratio < 1.0?

A

obsese individuals are less likely to have been exposed to a vegetable than the average control

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23
Q

approx how many people in the US are affected by CF? canada?

A

US: 30,000
CAD: 4,000

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24
Q

what is the birth incidence of Cf in canada?

A

1 in 3,600 births

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25
Q

what are the primary symptoms of CF?

A

the body produces an abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections (Pseudomonas aeruginosa and Staphylcoccus aureus are the main culprits)

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26
Q

what is a secondary symptom of CF?

A

thick secretions also obstruct the pancreas, preventing digestive enzymes from reaching the intestines. 85% of patients take pancreatic enzymes. Undiagnosed patients are often malnourished.

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27
Q

what used to be the standard diagnostic test for CF?

A

a sweat test, in which high salt levels indicated CF

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28
Q

what is the first step of newborn screening for CF in BC? under what conditions will this test be positive?

A

IRT (immunoreactive trypsinogen) test, which will return positive if pancreatic enzymes fail to enter the intestines and instead end up in the bloodstream

29
Q

which provinces screen newborns for CF as of 2018?

A

all of them
- 2014: new brunswick added
- 2015: nova scotia added
- 2016: all but quebec
- 2018: quebec added

30
Q

_____ led to the hypothesis that CF occurred in people who were homozygous for a recessive deleterious allele.

A

patterns of inheritance

31
Q

if you have two recessive alleles, who else that you know is also likely to have them? how does this relate to CF?

A

probs your family. CF is caused by 2 recessive alleles so the odds that someone random as both is very slim.

32
Q

how did romeo et al (1985) get data for their experiments on consanguineous marriages?

A

the pope kept a record between 1910 and 1962 that shows all the people in italy that married their 1st or 2nd cousin

33
Q

what did the results of the romeo at al 1985 study into consanguineous marriages and CF show?

A

Children with Cystic Fibrosis are 3.4x more likely to have parents that are 1st cousins and 4.3x more likely to have parents that are 2nd cousins than the average population.

34
Q

what did the results of the romeo study et al 1985 to conclude about the cause of CF?

A

that CF is caused by a recessive allele at a single locus

35
Q

what is the equation (Dalberg, 1947) that predicts the proportion of consanguineous marriages (C’1) among parents of children with a trait caused by recessive alleles at one locus if one knows the frequency of the recessive allele

A

C’1 = [C1(1 + 15q)]/(C1 + 16q – C1q)

36
Q

CF incidence estimated using ___________ is very close to the actual incidence observed in the population.

A

an equation by Dalberg (1947) and data from an archive of consanguineous marriages and from a questionaire

37
Q

frequency of 1st and 2nd cousin marriages among parents of kids with CF confirmed….

A

that CF was caused by a recessive allele at a single locus.

38
Q

how does the logarithm of odds (LOD) differ from the odds ratio (OR)?

A

LOD deals with genetic linkage while OR deals with the risk of exposure.

39
Q

LOD

A

linkage,

eg inheritance of blood type and nail patella syndrome

40
Q

a series of LOD scores are calculated from a number of proposed linkage distances:

A
  1. A linkage distance is estimated (eg. 0.2= 20% recombination)
  2. Given estimate, probability of a given birth sequence is given (eg. blood type A inherited with NPS)
  3. Value is then divided by probability of given birth sequence if genes are unlinked.
  4. Log of value is calculated and that is the LOD for that linkage distance

Same process is repeated with another linkage distance estimate. Linkage distance with highest LOD score is considered the estimate of the linkage distance.
Generally, want to receive a LOD over 3.
Add up linkages from each pedigree and add them together to receive overall LOD. Greater than 3 recombination frequency selected is over 1000 x more likely linked than non-linked.

41
Q

example of LOD for blood type and nail patella syndrome

A

First estimate: 0.125
First parent has parental genotype (A blood type and nail patella)
The probability of this event is 1-0.125 which equals 0.875
If unlinked, would be 1-0.5= 0.5
Then we look at pedigree.
Parental children= 7, Recombinant= 1
(0.875)^7(0.125)^1= 0.049, probability of birth seq given linkage
(0.5)^8= 0.0039, probability of birth seq given no linkage
Divide 0.049 by 0.0039 to get 12.56. The LOD will be 1.099.
Repeat for numerous linkage distances.
Highest LOD is at 0.125

42
Q

pedigree

A

Circle- female
Square- male
Black- affected individual
Black/ White- carrier

43
Q

LOD score = z =

A

Log [probability of birth sequence with a given linkage value / probability of birth sequence with no linkage]

44
Q

what two restriction enzymes are used for restriction fragment length polymorphism (RFLP) analysis

A
  1. hind III
  2. hinc II
45
Q

what 5 steps outline restriction fragment length polymorphism (RFLP) analysis?

A
  1. Isolate DNA
  2. Digest (w/ Hind III and Hinc II)
  3. Run fragments on a gel
  4. Transfer DNA from gel to a membrane
  5. Probe with complement (Southern Blot)
46
Q

what was used by Tsui et al. (1985) to probe their RFLP fragments?

A

a labelled lam4-9178 with a piece of complementary DNA (southern blotting)

47
Q

From their LOD score analysis of 39 families with CF children, what did Tsui et al. (1985) conclude was the linkage distance between the 5.3 cut site and the CF-causing mutation?

A

0.15 or ~15 million base pairs. Means there is an 85% chance that 5.3 is linked to this mutation.

48
Q

Once Tsui et al. (1985) had found the approximate location of the mutation causing CF, what 2 techniques were used to pinpoint its location?

A
  1. chromosome jumping
  2. chromosome walking
49
Q

Describe “chromosome jumping”.

A

DNA is digested with MboI, circularized with supF, re-digested with EcoRI, and cloned into a bacterial “library” before being probed with Lam4-917.

50
Q

Describe “chromosome walking”.

A

Design a primer to bind to the target sequence, sequence the DNA, go to the end of the new strand and make it the new primer, etc.

51
Q

When that LOD score is greater than ____, the recombination frequency selected is >1000 x more likely than the non-linked hypothesis

A

3.0

52
Q

What is the likelihood of a caucasian individual being a carrier for CF?

A

1 in 25

53
Q

approx ____ of CF patients have two copies of the delta 508 mutation

A

70%

54
Q

What makes the CFTR protein product non-functional?

A

It misfolds and is degraded before it can make it to the membrane (it would work fine if only it could get there).

55
Q

What is the most common mutation causing Cystic Fibrosis?

A

A single nucleotide ΔF508 deletion in the exon 10 of the CFTR sequence.

56
Q

proteopathy

A

a class of diseases in which certain
proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body

57
Q

ΔF508 causes the last nucleotide of an Ile to be lost. Why does this affect the following Phe and not the Ile?

A

Because the degenerative sequence still recognizes the first two bases as Ile, whereas the resulting frame-shift causes Phe to be lost

58
Q

How many other mutations (besides ΔF508) have been recorded in the CFTR as of 2024?

A

2117

59
Q

Is it possible/likely to have more than one mutation in the CFTR? What might be an effect of this?

A

Yes, since there are so many possible mutations. Some can have attenuating effects or cause alteration of clinical presentation of CF.

60
Q

What is a microsatellite?

A

A repetitive DNA sequence characterized by short motifs.

61
Q

Analysis of microdsatellites tells us…

A

tells us that most CFTR mutations are derived from a single mutational event (including delta F508)

62
Q

What was the sample group for the Handyside et al. (1992).

A

Three couples who all had at least one child with Cystic Fibrosis.

63
Q

What were the major methods of the Handyside et al. (1992) paper?

A
  1. Single blastomere biopsy
  2. PCR (with nested primers) of region containing ΔF508
  3. Heteroduplex analysis
64
Q

Why was heteroduplex analysis used in the Handyside et al. (1992) paper?

A

Because it is difficult to see the 3 base-pair difference in PCR products between the 5.3 and 6.3 cut sites.

65
Q

What were the odds that each couple in the Handyside et al. (1992) study would have had a healthy child without preimplantation genetic diagnosis?

A

75%

66
Q

What was the goal of the first successful clinical application of preimplantation genetic diagnosis?

A

To screen for males who might be hemizygous for an X-linked fragile X allele.

67
Q

Why is IntraCellular Sperm Injection the standard for in-vitro fertilization with preimplantation genetic diagnosis?

A

Because it avoids the chance of PCR amplifying DNA from sperm which didn’t actually fertilize the egg but where buried in the zona pellucida.

68
Q
A

BIOL 439 (2 decks)

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