Lecture 21: Chromosomal disorders Flashcards
What is the human karyotype of chromosomes?
46 Chromosomes
- 22 autosomes, pairs
- 2 sex chromosomes
Arranged in order of reducing size
What sort of cell is human karyotyping performed on?
Performed on any dividing cells
i.e Bone marrow, cancer, amniotic cells, chorionic villus, peripheral blood lymphocytes
What is useful of human karyotpying?
Gross screen of human genetic material
- Numerical and structural changes of chromosomes
Congenital disorders - Diagnostic info
Cancer - Diagnostic and prognostic info
What is the p arm, centromere, q arm and telomere of a chromosome?
P arm = Short arm
Centromere = Junction b/w long/short arm
Q arm = Long arm
Telomere = Cap found on long arm
What sort of chromosomal abnormalities can occur?
Numerical or structural
Constitutional vs acquired
What are the names given to changes in chromosome number?
Aneuploidy = Chromosome number that is not a multiple of the normal haploid number = 23
Monosomy, Trisomy
What is the cause of aneuploidy?
Non-disjunction during meiosis 1 or 2
How common are numerical chromosomal abnormalities?
- Up to 20% of pregnancies spontaneously abort
- Estimated 50% of these during first trimester are due to chromosomal abnormalities
- Most of these are numerical abnormalities
What are the clinical conditions of aneuploidy?
Down Syndrome
Turners syndrome
Klinefelter syndrome
What is the increasing risk factor for down syndrome and what is the clinical presentation?
Increased risk with increasing maternal age
Clinical presentation
- Cognitive impairment
- Characteristic facial features
- Others i.e Cardiac, GI, increased leukemia
What is klinefelter syndrome?
47, XXY
- Poor beard growth
- Breast development
- Under-developed testes
What is turners syndrome?
45, X0
- Characteristic facial features
- Web of skin, neck
- Constriction of aorta
- Poor breast development
- Under-developed ovaries
What is somatic mosaicism?
- Structural or numerical
- Occurs post zygote formation
- Mitotic non-disjunction i.e theres cells with normal chromosomes and cells with aneuploidy (mosiacism)
What are some structural chromosome abnormalities?
- Reciprocal translocations
- Robertsonian translocations
- Inversions
- Deletions
Constitutional or aquired
What is a reciprocal aka balanced translocation?
A two way exchange of material between two non-homologous chromosomes
Balanced typically = normal phenotype as no genetic material has been lost or gained
Unbalanced is rare
What happens to carriers of balanced translocation?
- Recurrent miscarriages
- Birth of dysmorphic baby who is an unbalanced carrier
- Oligiospermia
What is a robertsonian translocation?
Results from fusion of two acrocentric chromosomes to form one.
Phenotypically normal individual with only 45 chromosomes
What are two common robertsonian translocations?
der(13;14)
der(14;21) (unbalanced form of this is responsible for 4% of downs)
What is an inversion?
An intrachromosomal structural re-arrangement, which involves two breaks on the same chromosome- the resulting chromosome segment rotates by 180deg and re-inserts itself
Whats the consequence of inversion?
- Usually phenotypically normal
- 1 in 10,000
- Risk for producing unbalanced is very low
- inv(9), inv(2) and inv(Y) occur as normal pop variants
What are the types of chromosomal deletions?
Terminal deletion; Single break at the terminal region of a chromosome and loss of that fragment
Interstitial deletion; Two breaks in the same chromosome and loss of the intervening fragment
Whats an example of a chromosomal deletion?
Cri-du-chat syndrome
- del chromosome 15
- Severe mental retardation
- Cat-like cry at birth
What is conventional G-banding karyotyping used for?
Suspected congenital disorders
Cancer/leukemia
What is FISH used for?
Detection of;
- Duplication and deletions
- Translocations
What can be used in FISH?
Dividing and non-dividing cells i.e any cell type
