Lecture 5: Chromosomal Disorders Flashcards
Is p the short of long arm?
Short
What is polyploidy?
3 or 4 times of all chromosomes
What is aneuploidy?
Plus or minus one chromosome (45 or 47)
What are the two types of aneuploidy?
Monosomy
Trisomy
What is the cause of aneuploidy?
Non-disjunction
What are the 3 viable autosomal aneuploidies?
Down syndrome (21) Patau syndrome (13) Edward syndrome (18)
What are some features of Down syndrome?
Wide skull Tongue protruding Epicanthic above the eyes 15x chance of leukaemia Susceptibility to Alzheimers
What are some features of patau syndrome?
Cleft lip and palate
Defect in organs
Most die within a year
What are some features of Edwards syndrome?
Clenched fist
Rocker bottom feet
Heart and kidney abnormalities
Mean lifespan 5-15 days
What are the 3 sex chromosome aneuploidies?
XO – Turner syndrome
XXY – Klinfelter syndrome
XXX – Metafemale
What are some features of turner syndrome?
Poorly developed secondary sexual characteristics
Short stature
Sterile ovaries
What are some features of Klinefelter syndrome?
Male genitalia
Breast development
Female fat and public hair
What are examples of congenital disorders associated with chromosome deletion?
Chi-du-chat Prader Willis Angelmann Wolf-Hirschhorn syndrome Miller-Dieker Di-George
What are features of chi-du-chat syndrome?
Babies have cat like cry Defects in larynx Wide face Physical and mental retardation 5-15 years old
What is the best diagnostic tool for aneuplodies and large deletion?
Giemsa–stained karyotype
What are methods for detecting smaller chromosomal defects and disorders?
Fluorescence in situ hybridisation (FISH)
Array Comparative Genomic Hybridisation (Array CGH)
Single Nucleotide Polymorphism (SNP) profiling
Whole genome sequencing (non-invasive pre-natal diagnosis)
What does FISH consist of?
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)
What are limitations of FISH?
Small deletions/duplications cannot be detected
Can only test region corresponding to probe – need for prior knowledge
How does array comparative genomic hybridisation work?
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.
How do SNP arrays work?
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)
How does non-invasive pre-natal testing/ diagnosis?
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
