Lecture 5: Chromosomal Disorders

Question 1

Is p the short of long arm?

Answer 1

Short

Question 2

What is polyploidy?

Answer 2

3 or 4 times of all chromosomes

Question 3

What is aneuploidy?

Answer 3

Plus or minus one chromosome (45 or 47)

Question 4

What are the two types of aneuploidy?

Answer 4

Monosomy

Trisomy

Question 5

What is the cause of aneuploidy?

Answer 5

Non-disjunction

Question 6

What are the 3 viable autosomal aneuploidies?

Answer 6

Down syndrome (21)
Patau syndrome (13)
Edward syndrome (18)

Question 7

What are some features of Down syndrome?

Answer 7

Wide skull
Tongue protruding 
Epicanthic above the eyes
15x chance of leukaemia 
Susceptibility to Alzheimers

Question 8

What are some features of patau syndrome?

Answer 8

Cleft lip and palate
Defect in organs
Most die within a year

Question 9

What are some features of Edwards syndrome?

Answer 9

Clenched fist
Rocker bottom feet
Heart and kidney abnormalities
Mean lifespan 5-15 days

Question 10

What are the 3 sex chromosome aneuploidies?

Answer 10

XO – Turner syndrome
XXY – Klinfelter syndrome
XXX – Metafemale

Question 11

What are some features of turner syndrome?

Answer 11

Poorly developed secondary sexual characteristics
Short stature
Sterile ovaries

Question 12

What are some features of Klinefelter syndrome?

Answer 12

Male genitalia
Breast development
Female fat and public hair

Question 13

What are examples of congenital disorders associated with chromosome deletion?

Answer 13

Chi-du-chat
Prader Willis
Angelmann
Wolf-Hirschhorn syndrome 
Miller-Dieker 
Di-George

Question 14

What are features of chi-du-chat syndrome?

Answer 14

Babies have cat like cry 
Defects in larynx
Wide face
Physical and mental retardation 
5-15 years old

Question 15

What is the best diagnostic tool for aneuplodies and large deletion?

Answer 15

Giemsa–stained karyotype

Question 16

What are methods for detecting smaller chromosomal defects and disorders?

Answer 16

Fluorescence in situ hybridisation (FISH)
Array Comparative Genomic Hybridisation (Array CGH)
Single Nucleotide Polymorphism (SNP) profiling
Whole genome sequencing (non-invasive pre-natal diagnosis)

Question 17

What does FISH consist of?

Answer 17

Spread chromosomes on slide as for karyotype
Denature DNA of chromosomes in situ
Hybridise with fluorescently labelled probe corresponding to the region of interest
Wash off unbound probe
Stain DNA with fluorescent dye (DAPI)
View under a fluorescent microscope
Need to include control probe for unaffected region of same chromosome (different colour)

Question 18

What are limitations of FISH?

Answer 18

Small deletions/duplications cannot be detected

Can only test region corresponding to probe – need for prior knowledge

Question 19

How does array comparative genomic hybridisation work?

Answer 19

Microarray consisting of thousands of short DNA sequences spanning the entire genome
DNA from patient and control extracted and labelled with different fluorescent dyes (e.g. red and green)
DNAs mixed together in equal quantities and hybridised to the slide
Slide washed and scanned
Most spots will have equal red and green fluorescence
Deletion - relatively less green fluorescence in several spots
Duplication - excess of green fluorescence in several spots.

Question 20

How do SNP arrays work?

Answer 20

Microarray consisting of thousands of oligonucleotide pairs spanning genome
Each pair differs at single base
Hybridise with fluorescently labelled DNA from patient
Exact match required
Signal from both variants added together
Line up with genome and identify regions where signal is equivalent to single variant (if heterozygous)

Question 21

How does non-invasive pre-natal testing/ diagnosis?

Answer 21

Free DNA amplified and sequenced by NGS
Relative number of sequence reads used to measure chromosome number
Can be carried out from 9 weeks
Minimum of 5% foetal DNA required
May be used to detect aneuploidies, sex of foetus and some single gene mutations