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Alex's Genetics > Lecture 4a > Flashcards

Lecture 4a Flashcards

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Biology 101 flashcards
1
Q

When does crossing over occur?

A

Frequently in meiosis I and occasionally during mitosis.

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2
Q

If we crossover homologous chromosomes, what do we get?

A

New combinations of alleles.

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3
Q

If we crossover daughter chromosomes, what do we get?

A

Identical alleles to the original daughter chromosomes. There is no new combination of alleles.

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4
Q

Why does crossing over between sister chromatids produce no new allele combinations?

A

Sister chromatids are genetically identical. So, when we “exchange” physical pieces of the chromosome, it is just the same thing being switched out.

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5
Q

What is the genotype produced from crossover between sister chromatids?

A

All 4 haploid cells have their parental genotype.

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6
Q

Why does crossover of homologous chromatids produce new allele combinations?

A

Homologous chromatids are not genetically identical. So, when we cross these over, there is the potential to take something out and replace it with something completely different.

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7
Q

What do we call the genotype for new allele combinations?

A

Recombinant or nonparental genotype.

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8
Q

Why would we call the product of the crossover between homologous chromosomes the nonparental genotype?

A

Because the new allele combination is not the allele genotype of the parent, it is the product of the crossing over between one parent’s chromatid with the other parent’s chromatid.

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9
Q

What has meiosis most extensively been studied in?

A

Fungi

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10
Q

For meiosis in fungi, what is the final product?

A

Haploid spores

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11
Q

What is the fungal ascus?

A

It contains the spores produced by a single meiosis.

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12
Q

Explain Hickler’s process for examining gene recombination.

A

Hickler looked at a fungal cell whose homologous chromosomes differ at a single gene responsible for spore color. The fungal cell underwent meiosis and then the haploid alleles were assessed.

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13
Q

What was expected after the fungal cell’s homologous chromosomes with a single different gene underwent meisois?

A

The ratios were expected to yield 8 haploid cells, with a 4:4 ratio.

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14
Q

What did Hickler notice about the asci of the fungi after meiosis? What could not explain his observations? What term did he use to describe this phenomenom?

A

Some asci contained 6:2 ratios instead of the 4:4 ratios.

This was occurring at too high of a rate to be explained by new mutations.

Gene conversion

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15
Q

What term did Zickler coin?

A

Gene conversion

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16
Q

What is gene conversion?

A

This occurs when one allele is converted to the allele on the homologous chromosome.

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17
Q

In 1964, who proposed a model for homologous recombination?

A

Robin Holliday

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18
Q

What did Robin Holliday do?

A

Proposed a model for homologous recombination.

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19
Q

Was the Holliday model correct?

A

Yes, except for one detail.

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20
Q

What was incorrect about the Holliday model?

A

The Holliday model has homologous recombination initiating with 2 single stranded DNA breaks. It is actually 2 double-stranded DNA breaks.

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21
Q

What initiates the homologous recombination that occurs in meiosis?

A

Double-stranded breaks.

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22
Q

What type of studies showed that double-stranded breaks were responsible for initiating homologous recombination in meiosis?

A

Molecular studies in two different yeast species.

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23
Q

Who proposed the model for a double-stranded break?

A

Szostak, Orr-Weaver, Rothstein, and Stahl

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24
Q

Does the evidence more strongly favor single-stranded or double-stranded break models?

A

The evidence now strongly favors this double-strand break model.

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25
Q

Describe the double-stranded break model up to the displacement loop.

A

1) On one of the two homologous chromosomes, a double stranded-break occurs.
2) At the double-strand break site, degradation of the strand occurs to yield single-stranded ends.
3) The homologous chromosome with no strand break will invade with one of its strands, while the other homologous chromosome replaces that strand with one of its own, creating a D-loop (displacement loop) formation.

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26
Q

Describe the double-stranded break model from the displacement loop to the end.

A

1) With the D-loop, gap repair synthesis then takes place to fill in the vacant regions on both of the homologous chromosomes. Thus, there are two “crossovers” occurring.
2) Once the crossovers have happened, branch migration can occur, which leads to heteroduplexes.
3) To fix the heteroduplex, we rotate one of the two homologous chromosomes by 180 degrees.
4) The model can then be cut in two different ways to either produce non-recombinant DNA or recombinant DNA.

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27
Q

How would non-recombinant DNA look after its been cut? What way do we usually have to cut?

A

The allele combinations remain the same as before crossing over. Usually, a horizontal cut.

28
Q

How would recombinant DNA look after its been cut? What way do we usually have to cut?

A

There are new allele combinations for each homologous chromosome. Usually, a vertical cut.

29
Q

How often to DNA double-strand breaks occur?

A

10 to 50 breaks in every cell every day.

30
Q

Why are DNA double-stranded breaks dangerous?

A

Breaks can cause chromosomal rearrangements and deficiencies.

31
Q

How do we repair DNA double-stranded breaks?

A

Either Homology-Direct Repair (HDR) or Non-Homologous End Joining (NHEJ).

32
Q

What does Homology-Directed Repair entail?

A

It is an umbrella term for a number of related pathways.

33
Q

What is one pathway of HDR?

A

Homologous Recombination Repair (HRR)

34
Q

What is HRR?

A

It is basically the same pathway as during meiosis except that the double strand breaks were not deliberate.

So, we have the double stranded break, the strand exchange, DNA synthesis, and then the resolution and ligation.

35
Q

T/F: There are other forms of HDR that require only single strands of DNA as templates.

A

True

36
Q

Generally, what does single strand HDR look like?

A

Single stranded DNA will contain the specific change needed in the double-stranded break. Left and right homology arms will surround the area around the break and HDR will introduce the change.

37
Q

What is the dominant way of repairing double strand breaks in (non-stem) somatic cells?

A

Non-Homologous End Joining (NHEJ)

38
Q

Describe the process of NHEJ.

A

We are able to repair the double-strand break by joining the non-homologous ends.
1) End-binding proteins will attach to each side of the double-stranded break.
2) Proteins are recruited to form a crossbridge and for DNA processing. This processing can sometimes result in the deletion of a small region of the double-strands.
3) The broken ends are then pieced back together.

39
Q

What is Non-Homologous End Joining?

A

The dominant method to repair double-strand breaks in (non-stem) somatic cells.

40
Q

What are stem cells?

A

They are the cells that construct our bodies from a fertilized egg by making many different cell types.

41
Q

What do stem cells do in adults and how common are they?

A

Stem cells also replace damaged cells. They are rare in adults.

42
Q

With stem cells, what is the dominant pathway for repairing double-stranded breaks?

A

Homology-Directed Repair (HDR) pathways

43
Q

What are the types of stem cells?

A

Totipotent, unipotent, multipotent, pluripotent.

TUMP

44
Q

What do totipotent cells do?

A

They can give rise to all cell types, just like fertilized eggs.

45
Q

What do pluripotent cells do?

A

They can differentiate into almost every cell, but they cannot give rise to an entire, intact individual.

46
Q

What do multipotent cells do?

A

They differentiate into several cell types.

47
Q

What do unipotent cells do?

A

They are only able to differentiate into one cell type.

48
Q

Where would we find totipotent cells?

A

A fertilized egg is totipotent. They are able to give rise to an entire, intact individual.

49
Q

Where could we find pluripotent cells?

A

Embryonic stem cells (ES cells) are pluripotent. These are in the blastocyst, which floats around before implanting into the uterine wall to become the embryo and then the fetus.

Once, we have the fetus, embryonic germ cells (EG cells) are also pluripotent.

50
Q

Where would we find multipotent and unipotent cells?

A

They many types of adult stem cells are multipotent or unipotent.

51
Q

Where does blood come from?

A

Stem cells that are multipotent.

52
Q

How do stem cells become red blood cells?

A

A stem cell undergoes cellular division and then differentiation to become a red blood cell.

53
Q

What kind of multipotent stem cell will turn into a red blood cell?

A

A hematopoietic stem cell divides to become a hematopoietic progenitor before differentiating into a myeloid progenitor and then a red blood cell.

54
Q

In the 1980s, what 2 things did scientists determine in regards to Embryonic stem cells (ES cells)?

A

Scientists learned:
1) how to obtain and culture pluripotent ES cells in the lab.
2) how to introduce mutations into ES cells using homologous recombination.

55
Q

How could ES cells be using to introduce mutations?

A

Using homologous recombination, genes could be modified at their native chromosomal positions.

56
Q

T/F: People tried deriving ES cells from the embryos of other mammals including humans and were quite successful!

A

False, it was very difficult to do this and the cells obtained had issues.

57
Q

What did Shinya Yamakaka show in 2006?

A

We could convert adult cells into pluripotent stem cells by introducing four specific genes that encoded transcription factors.

58
Q

What are induced pluripotent stem cells (iPS cells or iPSCs)?

A

Pluripotent cells that were derived from adult cells.

59
Q

What kinds of cells can become induced pluripotent stem cells?

A

These cells can be generated directly from any adult cells that have a diploid nucleus.

60
Q

What was Yamakaka awarded the nobel prize for?

A

For the discovery that mature cells can be reprogrammed to become pluripotent.

61
Q

What did Yamakaka hypothesize?

A

He believed that genes important to embryonic stem cell function might be able to induce an embryonic state in adult cells.

62
Q

How did Yamaka identify the four genes?

A

He chose 24 genes important in embyronic stem cells and used retroviruses to deliver these genes to mouse fibroblasts. He then removed one gene at a time from the 24 and identified the 4 that were necessary to generate embryonic stem cell colonies.

63
Q

What were the 4 genes Yamaka identified?

A

Oct4, Sox2, cMyc, Klf4

64
Q

Why are iPS cells so important?

A

They represent a single source of cells that could be used to replace those lost to damage or disease.

65
Q

Why is it not currently feasible for us to create patient-matched embryonic stem cell lines?

A

Embryonic stem cells can only be derived from embryos. Thus, this isn’t feasible.

66
Q

Why would iPS cells be important for transplants?

A

They are an unlimited supply that could generate transplants without the risk of immune rejection.

67
Q

What are iPSCs being used for now?

A

They are being used in personalized drug discovery efforts and understanding the patient-specific basis of disease.

Alex's Genetics (38 decks)

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