Chromosome disorders

Question 1

G banding

Answer 1

Heterochromatin stained
Each chromosome has characteristic banding pattern
Short arm (p), long arm (q)

Question 2

Polyploidy

Answer 2

Triploidy (3N)
Tetraploidy (4N)
All pairs have an extra or 2 extra chromosomes

Question 3

Aneuploidy

Answer 3

One less chromosome in a pair (monosomy)
One more chromosome in a pair (trisomy)
Caused by non-disjunction in meiosis (1 or 2).
Only 3 types allow for survival (21, 13 and 18)

Question 4

Down syndrome

Answer 4

Trisomy 21
Wide skull, flattened at back
Furrowed and protruding tongue
Epicanthic fold above eyes
Susceptibility to Alzheimer's

Question 5

Patau syndrome

Answer 5

Trisomy 13
Physical and mental effects
Cleft lip and palate
Defects in multiple organ systems
Most die within a year

Question 6

Edwards syndrome

Answer 6

Trisomy 18
Rocker bottom feet
Clenched fist
Internal abnormalities
Lifespan of 5-15 days

Question 7

Turner syndrome

Answer 7

XO aneuploidy
Poorly developed secondary sexual characteristics
Short stature, broad chest, webbed neck
Rudimentary ovaries (sterile)

Question 8

Klinefelter syndrome

Answer 8

XXY aneuploidy
Male genitalia
Breast development
Female characteristics
Low fertility

Question 9

Chromosome rearrangements

Answer 9

Crossing over between repetitive DNA
If out of line pairing, deletion in one chromosome and duplication in the other occurs
If hairpin forms in one, this is recombined and snipped out
Reciprocal translocation occurs when different chromosomes are crossed over

Question 10

Cri-du-chat syndrome

Answer 10

Deletion at 5p15
Cat like cry (defects in glottis and larynx)
Wide face and saddle nose
Physical and mental effects
Severity depends on extent of deletion

Question 11

Giemsa stained karyotype

Answer 11

Best for aneuploidies and large deletions/duplications
Time consuming and can’t detect small rearrangements

Alternatives are FISH, array CGH, SNP, WGS

Question 12

Microdeletions

Answer 12

Occur spontaneously due to recombination between repeated sequences

Question 13

FISH

Answer 13

Fluorescence in situ hybridisation
Chromosomal DNA hybridised with fl. labelled probe corresponding to target
Stained with fl. dye and viewed under a fluorescent microscope

Commonly used for chromosomes 13, 18, 21, X and Y

Question 14

FISH limitations

Answer 14

Small deletions/duplications cannot be detected

Prior knowledge needed (only tests for region that probe is made for)

Question 15

CGH

Answer 15

Array Comparative Genomic Hybridisation
Microarray with short DNA sequences spanning entire genome
Patient and control DNA labelled with dyes, mixed and hybridised to a slide
Relative amounts of staining indicate deletion/duplication

Question 16

SNP arrays

Answer 16

Microarray with oligonucleotide pairs spanning genome
Each pair differs at single base
Hybridised with labelled patient DNA
Signal from both pairs added together

Question 17

NIPT

Answer 17

Non-invasive pre-natal testing
Free maternal DNA (10% is foetal) sequences by NGS
Relative number of sequence reads used to measure chromosome number

Question 18

Most common terminal deletion in humans

Answer 18

1p36 deletion
Developmental delay
Vision problems
Intellectual disability
Varying phenotypes due to heterogeneity of mutations (terminal or interstitial mutations of varying lengths)