11 - Intro to Cytogenomics

Question 1

Medical cytogenomics

Answer 1

• Studies gross human genome variation in health and disease
• Involves heredity at the cellular level

Question 2

Human chromosomes

Answer 2

23 pairs (22 autosomes, 1 sex chromosome)

Question 3

p arm

Answer 3

Short

Question 4

q arm

Answer 4

Long

Question 5

Methods for cytogenomic analysis

Answer 5

• Conventional cytogenetics
• Chromosomal microarray
• Fluorescence in situ hybridisation (FISH)
• Quantitative fluorescence PCR (QF-PCR)
• Genomic sequencing

Question 6

Conventional genetics

Answer 6

• Requires dividing cells
• Resolution 5-10Mb

Question 7

FISH

Answer 7

• Dividing/non dividing cells
• Resolution ~200Kb

Question 8

Chromosomal microarray

Answer 8

• DNA based
• Resolution ~50Kb

Question 9

QF-PCR

Answer 9

• DNA based
• Resolution single locus

Question 10

Genomic sequencing

Answer 10

• DNA based
• Single nucleotide resolution
• Both sequence and structural info

Question 11

Chromosome abnormalities

Answer 11

Deviations from the standard pattern of 23 pairs of chromosomes with known morphology (can be numerical or structural)

Question 12

Numerical chromosome abnormalities

Answer 12

• Deviations in chromosome number (trisomy 21)
• Usually occur de novo (low recurrence risk)

Question 13

Mechanism of numerical chromosome abnormalities

Answer 13

Cell division errors or fertilisation errors

Question 14

Cell division errors

Answer 14

• Checkpoint defects
• Cohesion defects
• Centrosome amplification
• Microtubule defects

Question 15

Fertilisation errors

Answer 15

Dispermy / trispermy

Question 16

Euploid numerical abnormalities

Answer 16

Multiples of the haploid set (triploid, tetraploid)

Question 17

Aneuploid numerical abnormalities

Answer 17

Gain or loss of one or a few chromosomes (trisomy 21, monosomy X)

Question 18

Structural chromosome abnormalities

Answer 18

• Chromosomal breakage and reunion in a different configuration
• Can be balanced (no net gain or loss), or unbalanced (gain/loss of chromosomal material)
• May be inherited

Question 19

Robertsonian translocations

Answer 19

• Translocation of chromosome 21 to chromosome 14 (45 chromosomes present)
• Risk for chromosomally abnormal offspring (translocation trisomy 21)

Question 20

Metacentric

Answer 20

p arm = q arm

Question 21

Submetacentric

Answer 21

p arm shorter than q arm

Question 22

Acrocentric

Answer 22

Really short p arm with regular q arm

Question 23

Balanced translocations

Answer 23

• Robertsonian translocation
• Reciprocal translocation

Question 24

Paracentric

Answer 24

Inversion on one side of centromere

Question 25

Pericentric

Answer 25

Inversion involving the centromere

Question 26

Unbalanced structural abnormalities

Answer 26

• Deletion
• Duplication
• Interstitial deletion
• Sister chromatid recombination (isochromosome)
• Loss of borth termini (ring chromosome)

Question 27

Mosaicism

Answer 27

Presence of cell lines with different chromosomal constitution in the same individual (numerical or structural changes)

Question 28

Clinical impact of cytogenomic variants

Answer 28

• No apparent effect
• Reproductive issues
• Congentital anomalies
• Developmental issues
• Cancer