Topic 11a: Cytogenic analysis of chromosomes Flashcards
trisomy
Chromosomal abnoramilities account for a large proportion of which conditions/diseases?
- spontaneous abortions,
- congenital anomalies,
- intellectual disabilities,
- infertility
what affects the risks associated with chromosomal imbalances or abnormalities?
- presence of haploinsufficient or triplosensitive genes in deleteted or duplicated segemnts
- the global/ cumulative effect of multiple genes on development
- generally, loss or gain of a while chromosome leads to substantial risk of disease (smaller changes can be ok)
what is the cause of the most common muations seen in humans?
aneuploidy (errors in chromosome segregation)
Name the three well-defined non-mosaic autosomal chromosome aneuploidy compatible with postnatal survival?
- Trisomy 21 (down’s syndrome)
- Trisomy 18 (Edward’s syndrome)
- trisomy 13 (patau syndrome)
why is it that we only see 3 compatible types of aneuploidies?
when involves chromosomes in gene-rich regions, it is incompatible with longterm survival and is frequently associated with pregancy loss
Of the conceptions that abort in the first trimester, what the most common cause?
chromosome anomalies (~50%), where the majority of these abnormalities are trisomies that are negatively selected for in the first trimester)
Triploidy is often the result of what?
noraml ovum fertilized by two sperms or by a diploid sperm
How will the majority of all trisomy 21 pregnancies conceived end?
`
spontaneous abortion
what is the most common genetic cause of moderate intellectual disability?
Down’s syndrome
What is the most frequent karyotype of Down’s syndrome?
47, +21 (95% of all patients)
what is non-dysjunction?
the process by which two homologous chromosomes or 2 sister chromatids migrate to the same pole as opposed to opposite poles during cell division
what are the 3 places that nondyjunction can occur?
- meiosis 1 (chromosome pairs do not seperate)
- meiosis 2 (chromatids do not seperate)
- mitosis (leads to mosaicism)
what is known to be correlated to increased chance of aneuploidy? why do people think we see this?
maternal age: which is linked to loss of cohesions between chromatids
Mechanism of origin of down’s syndrome
Meiotic nondisjunction (most common) but can also be caused by mitotic nondysjunction
when does the nondysjunction event leading to down’s syndrome typically occur?
maternal meiosis (M1) mostly (90%) and other 10% occurs in paternal meiosis
what cytogenic diagnostic techniques can be used to investigate trisomy 21 cases?
- quantitative fluorescent PCR
- chromosome banding
- FISH
- chromosomal microarray
what is QF-PCR?
During capillary electrophoresis, the amplified fluorescent microsatellites fragments of different lengths will migrate at different speed and the fluorescence is measured.
what are the advantages of QF-PCR?
- Fast turn-around-time for reporting (no need to culture)
- Automated
what are limitations of QF-PCR?
it is a targeted approach; allows detection og common trisomies and monosomies only
what is chromosome banding?
Will produce distinctive and reproducible patterns of transverse light and dark bands along the chromosomes
what are advantages of chromosome banding?
- View of all the chromosomes of one cell
- Can study multiple individual cells
- Can detect balanced and unbalanced rearrangements
what are limitations of chromosome banding?
- Limit of resolution around 5 -10 Mb
- Need an actively growing source of cells
What is FISH?
A DNA probe labeled with a fluorescent dye hybridize directly to the metaphase or interphase chromosome. A fluorescent signal identifies the probe on a specific region of the chromosome.
what are the advantages of FISH?
- Higher resolution as compared to G banding
- Can study non-dividing or fixed tissues
- Shorter turn-around time (TAT)