Test2: Lect 11 Susan Olson

Question 1

Resolution of standard karyotyping:

Answer 1

Haploid genome

Whole genome

Question 2

Routine banding vs high res banding:

• Difference?
• Resolution?
• Done how?

Answer 2

- Difference?
Routine banding: during Metaphase (chromosomes are more condensed)
During prophase, chromosomes are longer
- Resolution?
About 5x better in high res.
range of millions of BPs
- Done how?
G-banded chromosome staining

Question 3

FISH analysis:

- Resolution?

Answer 3

• Resolution?

50 - 250,000 bp

Question 4

Chromosomal microarrays:

- Resolution?

Answer 4

• Resolution?

50 - 250,000 bp

Question 5

Whole genome sequencing

- Resolution?

Answer 5

• Resolution?

1 - 1000 bp

Question 6

Metacentric:
Acrocentric:
telocentric:

Answer 6

centromere in middle
between middle and end
centromere at the end of chromosome

Question 7

Triploidy:

Answer 7

• Caused by fertilization with two sperm

- Lethal

Question 8

Aneuploidy:

Answer 8

1 extra or 1 missing chromosome

Question 9

Down syndrome:

• Type of aneuploidy:
• Most common cause:
• How can someone be a carrier?

Answer 9

• Type of aneuploidy:
  Trisomy 21
• Most common cause:
  Non disjunction in meiosis 1 or 2
• How can someone be a carrier?
  They can have 1 copy of chromosome 21, which is actually two copies of 21 fused to each other.
  There is no way for separation to occur, so essentially there will always be non-disjunction at meiosis 1

Question 10

At what age does aneuploidy risk sky rocket?

Answer 10

Age 35 for women

Question 11

Turner syndrome:

Answer 11

1 X chromosome

Question 12

Klinefelter syndrome:

Answer 12

XXY

Question 13

How could you test to see if you have a large scale chromosomal deletion syndrome like 4P?

Answer 13

G-banded chromosome staining, possibly with high resolution.

Fish would be another possibility

Question 14

Large scale translocation between two chromosomes:

• Phenotype:
• Ability to have children?

Answer 14

• Phenotype:
  They will be normal
• Ability to have children?
  Quadrivalent chromosome alignment, can result in normal child or abnormal or abortion.

Question 15

Pericentric inversion vs paracentric:

Answer 15

Pericentric inversion which includes the centromere
Paracentric inversion which does not.
- What happens when you have an odd number of crossing over events?

Question 16

Pericentric:

- What happens when you have an odd number of crossing over events?

Answer 16

For ABCD x ACBD
1 : 4 normal ABCD
1 : 4 Deletion A duplication D  DCBD
1 : 4 Deletion D duplication D  ABCA
1 : 4 Inverted still ACBD

Question 17

Paracentric inversion:

- What happens when you have an odd number of crossing over events?

Answer 17

Usually the chromosome is inviable. You cannot pass this chromosome on.

Question 18

Isochromosome:

• Define:
• Example:

Answer 18

- Define:
Mutation where the arms of the chromosome are mirror images of each other.
- Example:
ABC (centromere) CBA
Turner Syndrome

Question 19

X chromosome translocation:

Answer 19

A portion of the X chromosome can translocate to another chromosome. If it is does and the person is female then inactivation of that X will inactivate the chromosome it is on as well

Question 20

Chromosomal mosaicism:

• Define:
• Issue with prenatal screen testing:

Answer 20

• Define:
  Some point post zygote a cell gains aneuploidy of chromosome. Its progeny are aneuploid as well
• Issue with prenatal screen testing:
  Prenatal screening tests placenta, which is made by uterus, with mosaicism there could be aneuploidy in the fetus or in the placenta or in both or in neither. If it is in the placenta and not the fetus then there will be a false positive.

Question 21

Suppose you have trisomy 21, 2 from your mom one from your dad. But one chromosome is lost, ‘fixing it’. What could still go wrong?

Answer 21

If i lost either of the maternal chromosomes then I still have the right amount of paternal and maternal. Because of imprinting, if I lose my only paternal, some genes will not be expressed within me, and some genes will be overexpressed.

Question 22

Uniparental disomy:

• Define:
• Identification?

Answer 22

• Define:
  Two copies of the same chromosome from one parent. Over-express maternal or paternal genes, do not express the others.
• Identification?
  G-banded chromosome staining (Dark regions will be heterochromatin, if the gene is being differentially expressed it is likely there is differential patterns of heterochromatin as well)

Question 23

HETERODISOMY:

Answer 23

parent passes on one copy of each homolog (non-disjunction in meiosis I)

Question 24

ISODISOMY:

Answer 24

parent passes on two copies of the same chromosome (non-disjunction in meiosis II)

Question 25

Cancer and chromosomal abnormalities: | - Types:

Answer 25

``` - Types: Balanced chromosomal rearangements (translocation (no loss of material) Chromosomal imbalances (deletion or duplication) ```

Question 26

How can balanced chromosomal rearrangements cause cancer?

Answer 26

2 ways: - rearrangement lands in a new regulatory environment, and differential expression causes cancer - rearrangement lands in a an important element, disrupts it - rearrangement results in a new protein product

Question 27

Philadelphia Rearrangement: - define: - BCR/ABL Fusion by Interphase FISH:

Answer 27

- define: Switch between chromosome 9 and 22, results in aberrant protein, causes cancer. - BCR/ABL Fusion by Interphase FISH: This fusion is what causes the increased risk for cancer. Normal signal pattern = 2 red/ 2 green Fusion signal pattern = 1 red/ 1 green/ 2 yellow

Question 28

FISH: - Define: - common uses:

Answer 28

- Define: DNA probe, labelled fluorescent, binds to and marks if the probe sequence is present. - common uses: 1. Absence of hybridization may uncover submicroscopic deletion 2. Used when there is a question of a deletion based on family history or suspicious-looking karyotype. 3. Used to map specific genes or arbitrary sequences to a chromosome region. 4. Used for rapid detection of abnormal chromosome number (interphase)

Question 29

Which chromosomes can survive trisomy?

Answer 29

13, 18, 21 and X chromosome

Question 30

Ring chromosome:

Answer 30

Seen more often in cancer

Question 31

Interphase FISH Analysis: | - Uses?

Answer 31

- Uses? Monitoring BCR/ABL Fusion by Interphase FISH Rapid trisomy screening

Question 32

Chromosome Paints - Broad: - Specific:

Answer 32

- Broad: 1. Cocktail of genome or chromosome-specific probes. 2. Delineation of chromosome rearrangements. 3. Chromosome/marker identification - Specific: 1: Color all human chromosomes one color, all mice another 2: color two chromosomes different colors, so you can check if they've fused more easily

Question 33

``` Multicolor FISH (M-FISH) and Spectral Karyotyping (SKY): ```

Answer 33

Gives every chromosome its own color

Question 34

Array Comparative Genomic Hybridization: | - Define:

Answer 34

- Define: 1: Like giant fish assay, but probes are attached to a chip. SNPs are what is being identified. 2: Add your patients DNA labelled green and control DNA labelled red 3: yellow wells are normal. Red wells suggest a deletion. Green wells suggest a duplication

Question 35

Non-allelic Homologous Recombination (NAHR) can cause:

Answer 35

duplication and deletion