Chromosome disorders Flashcards
Chromosome Nomenclature:
What is the p arm, centromere, q arm, telomere
What does 9p34 mean?
Label diagram
Lecture Slide
9 = chromosome number
p = short arm
34 is the part of the chromosome that is abnormal
What can chromosome Abnormalities be catergorised as
give examples
Numerical or structural
- Down syndrome
Constitutional vs acquired
-acute leukemia (acquired)
What do you call
loss of 1 chromosome
gain of 1 chromosome
Caused by?
Aneuploidy:
Chromosome number that is not a multiple of the normal haploid number (=23)
Loss of 1 chromosome = monosomy
Gain of 1 chromosome = trisomy
Caused by non disjunction during meiosis
Trisomy 21 (down syndrome)
- risk factor for getting DS child
-clinical features of DS
RISK INCREASES WITG MATERNAL AGE
Clinical features
Cognitive impairment Characteristic facial features
Other abnormalities eg cardiac, increase risk of leukaemia, GI
Clinical features of klinefelter syndrome (chromsome number change) and turner syndrome (chromosome number change)
Klinefelter syndrome 47, XXY
- Breast development, poor beard growth, underdeveloped testes
Turner syndrome 45, X0
- Characteristic facial features, web skin, constriction of aorta, poor breast development, underdeveloped ovaries
Structural chromosome abnormalities:
Mutation types
- Reciprocal translocations 2. Robertsonian
- translocations Inversions
- Deletions
A reciprocal and balanced translocation is …
a two way exchange of material between two non-homologous chromosomes.
A balanced translocation results in a phenotypically normal individual as no genetic material has been lost or gained
Unbalanced vs balanced translocation draw it
Lecture Slide
How do carriers of reciprocal (balanced) translocations present?
- Recurrent miscarriages
- Chromosome examination of products of conception
- Birth of a dysmorphic baby who is an unbalanced carrier
- Oligospermia in male carriers
What is A Robertsonian translocation…
results from the fusion of two acrocentric chromosomes (i.e. chromosomes 13, 14, 15, 21 or 22) to form one chromosome.
A phenotypically normal individual will have 45 chromosomes, not 46!
Draw a Robertsonian translocation
Lecture Slide
two most common Robertsonian translocations
der(13;14)
der(14;21)
Cause 4% of down syndrome cases
An inversion is …
an intra-chromosomal structural rearrangement, which involves two breaks on the same chromosome - the resulting chromosome segment rotates by 180o and reinserts itself
Types of inversions and drawings
Pericentric - involves centromere and both sides of it
Paracentric - involves just one half of the chromosome, no centromere
Lecture Slide
Do inversions make normal phenotype?
Inversion carriers are usually phenotypically normal
Chromosome Deletions types
- explain and draw
A terminal deletion is caused by a single break at the terminal region of a chromosome and loss of that fragment.
An interstitial deletion is caused by two breaks in the same chromosome and loss of the intervening fragment.
Lecture Slide
Genetics testing from broadest detection to DNA detection of error
G banding, FISH, Mutation screening, Sequencing
Chromosome level: Aneuploidy, Duplication, deletion, translocation THEN microdeletion THEN point mutations at DNA level
What is Cri-du-chat syndrome
- symptoms
-chromsome cause
Severe MR (IQ<20)
- cat-like cry at birth
-very poor speech
-inability to walk
-premature ageing
del 5p15.1
Conventional (G-banding) Karyotype analysis
- how broad is it?
- examples of what it can help diagnose?
G banding looks at the karotype:
Suspected congenital disorders
eg Down syndrome, -dysmorphic baby
- Products of conception
-Recurrent miscarriages
Cancer / Leukaemia
Diagnostic and prognostic marker Therapeutic decisions
What is FISH
Fluorescence In Situ Hybridization
This technique exploits the ability of a given DNA molecule to bind specifically - or hybridize - to the DNA template from which it originated.
Draw the process of FISH
Lecture Slide
FISH and Chromosome Analysis
-requires what
-looks at?
Karyotype analysis requires dividing cells whole genome scan
FISH = an adjunct to chromosome analysis; looks at specific genes / parts of genes only
Specimens suitable for FISH
Any type of tissue with a viable nucleus
Blood, Skin, Bone marrow, tumours, amniocytes, paraffin embedded tissues
Dividing and non-dividing cells
Breast cancer pathology using FISH, explain what it would look like
Lecture Slide
What would FISH look like for trisomy 21
Lecture SLide
