WK2 - Cytogenetics Part I & II

Question 1

What is a chromosomal abnormality?

Answer 1

abnormality in:

• number of chromosomes
• deletion or duplication of part of a chromosome
• rearrangement between two chromosomes resulting in imbalance - ie. an unbalanced rearrangement

Question 2

What does a centromere do?

Answer 2

attaches the DNA molecule to the mitotic spindle

Question 3

What is a telomere?

Answer 3

DNA sequence of repeats at each end of the chromosome

Question 4

What is euchromatin?

Answer 4

• relatively high frequency of coding regions or genes
• bands define alternating partitions of euchromatin
• transcriptionally active

Question 5

What is heterochromatin?

Answer 5

• area devoid of genes or containing inactive genes; ie. transcriptionaly inactive areas
• these areas tend to remain highly condensed throughout cell cycle
• contains highly repetitive elements
• demonstrate with C banding or fluorescent staining

Question 6

What is constitutive heterochromatin? And where are they found in chromosomes?

Answer 6

• always in the inactive state
• composed largely of certain repetitive DNA sequences
• found in centromeres, Yq, p arms of acrocentric chromosomes

Question 7

What is facultative heterochromatin? Give an example.

Answer 7

• can be genetically active or inactive

- specialized case is mammalian X which may undergo chromosome inactivation

Question 8

What is X inactivation?

Answer 8

• most genes on the X chromosome do not have a counterpart on the Y chromosome
• needs to be a mechanism for dosage compensation; ie. turn off the genes that have more than 1 copy
• early in embryogenesis, one X chromosome in each cell randomly inactivates (some genes stay active)
• the initial inactivation persists in all the subsequent mitotic divisions of that original cell
• each normal female is then a mosaic for the active X chromosome

Question 9

What is a Barr body?

Answer 9

• the inactivated X chromosome is seen in the cell as a Barr body

Question 10

What type of banding are there?

Answer 10

• G (Giemsa) banding
• R (reverse) banding
• C banding (highlights centromere, long arm, etc.)

Question 11

What is the order you get the least chromosome band to the most in the following harvesting time:

• routine preparation
• amniocentesis
• prometaphase

Answer 11

1. amniocentesis - 400-500 bands (can miss things because don’t get too much info)
2. routine preparation - 550 bands
3. prometaphase - 750 to 800 bands ( generally used to look at detail)

Question 12

Define fluorescent in-situ hybridization (FISH), when it hybridize and what it help look for.

Answer 12

• specific single-stranded DNA probes labelled to fluoresce
• can be hybridized to metaphase chromosomes or to interphase nuclei
• can paint or look for specific deletions (but cannot differentiate whether a mutation is a consequence of nondisjunction or translocation)

Question 13

What is microarray comparative genomic hybridization and what does it look for?

Answer 13

• compares normal to patient DNA analyzing multiple area on the chromosome
• look for imbalances such as duplicates or deletions

Question 14

What is copy number variants (CNVs)?

Answer 14

• fewer or more than the expected number of copies of a genomic region
• the molecular equivalent of aneuploidy
• may contain few to many genes whose function may or may not be known
• benign CNVs are frequent
• most benign CNVs are inherited polymorphisms

Question 15

What is polyploidy?

Answer 15

multiples of haploid set of chromosomes

Question 16

What is triploidy and what does the phenotype look like?

Answer 16

3 sets of chromosomes - almost never seen in live births

Question 17

What is aneuploidy?

Answer 17

• fewer or more chromosomes than the exact multiple of the haploid set
• this includes trisomy and monosomy
• trisomies are the most frequent; monosomies (other than monosomy X) are often lethal

Question 18

What is nondisjunction and when can it happen during cell division?

Answer 18

• failure of a pair of chromosomes to disjoin in the normal way
• may happen in MI or MII of meiosis or in mitosis

Question 19

What is the consequence of MI error?

Answer 19

• gamete contains 24 chromosomes instead of 23

- contains both pat and mat members of the pair

Question 20

What is the consequence of MII error?

Answer 20

• gamete contains 24 chromosomes instead of 23

- contains both copies of either mat or pat chromosomes

Question 21

At what maternal age does the risk of aneuploidy start to increase?

Answer 21

32 year old

Question 22

What is monosomy?

Answer 22

• all of a chromosome missing
• lethal unless 45, X
• can be the consequence of anaphase lag, less often nondisjunction
• NOT associated with advanced maternal age

Question 23

What is Turner syndrome?

Answer 23

• about half of Turner syndrome is 45, X

- others have one normal X and one abnormal X (with deletions or other rearrangements)

Question 24

What is an isochromosome?

Answer 24

• choromosome with one arm missing, one arm duplicated; sister chromatid exchange likely
• individual is partially monosomic; partially trisomic
• most commonly seen as subtype of Turner syndrome when X involved
• karyotype: 46. X.i(X)(q10)

Question 25

What can result in deletion?

Answer 25

1. chromosome breakage with loss of segment
2. unequal crossing over
3. abnormal segregation of translocation

Question 26

What are micro deletion syndromes? What methods can be used to detect them?

Answer 26

• recognizable syndrome secondary to a specific microdeletion (not seen in metaphase chromosomes)
• sometimes seen in high resolution banding, with FISH probes or Array CGH

Question 27

What are inversions? What are the two types?

Answer 27

• single chromosome undergoes two breaks
• reconstituted with segment between breaks inverted
• paracentric - beside the centromere (2 breaks occur in one arm)
• pericentric - around the centromere (2 breaks occur in both arms)

Question 28

What are translocations?

Answer 28

• exchange of 2 chromosomal segments between two usually non-homologous chromosomes

Question 29

Define reciprocal translocation.

Answer 29

• reciprocal exchange of the broken off segments between two chromosomes
• the derivative chromsomes are the products of the exchange

Question 30

Define Robertsonian translocation.

Answer 30

Fusion of two acrocentric chromosomes near the centromere

Question 31

What are acrocentric chromosomes and which chromosomes are they?

Answer 31

• chromosomes 13, 14, 15, 21 and 22

- satellited short arms which carry genes for rRNA

Question 32

What are the age related risk for trisomy 13, 18 or 21 in any pregnancy?

Answer 32

• 1 to 2 %

- or age related risk if over 35 years old

Question 33

What are the age related risk for trisomy 21 in a Robertsonian t(14;21) female carrier?

Answer 33

10%

Question 34

What are the age related risk for trisomy 21 in a Robertsonian t(14;21) male carrier?

Answer 34

2%

Question 35

What are the age related risk for trisomy 21 in a t(21;21) male carrier?

Answer 35

100%

Question 36

What are the age related risk for trisomy 21 in a t(21;21) female carrier?

Answer 36

100%

Question 37

What are the risk for trisomy in a carrier with reciprocal translocations?

Answer 37

30 to 40 %

Question 38

What are the indications for Karyotyping?

Answer 38

1. Problems of early growth and development – failure to thrive, development delay, multiple malformations, short stature
2. Stillbirth and Neonatal death
3. Infertility or recurrent spontaneous abortions
4. Family history of chromosome problem
5. Tumors (the tumor itself)
6. Advanced maternal age (the pregnancy)

Question 38

What are the risk for trisomy in a carrier with inversions?

Answer 38

up to 5 to 10 %