Genetic Test Flashcards
Genetic test
Xp22.3 chromosome x arm p region 2 brand 2 subband 2
Types of chromosomal aberrations
- Numerical
2. Structural
Types of structural variation
Insertions Deletions Duplications Inversion Translocation
Unbalanced translocation
Translocation where the exchange of chromosome material is unequal resulting in extra or missing genes
Balanced translocation
Translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality)
Which types of structural variants are balanced vs unbalanced?
Insertions, Deletions, Duplications are unbalanced
Inversion are balanced
Translocation can be both
derivative chromosome
chromosome that has an intact centromere
acrocentric chromosome
having the centromere situated so that one chromosomal arm is much shorter than the other — compare metacentric, telocentric entry 1
Karyotype
Changes in the number of chromosomes
Deviations from normal banding patterns Large (>5-10Mb) insertions or deletions, translocations and inversions
from one cell
Fluorescent in situ hybridization (FISH)
employs a fluorescently labeled probe to detect and localize the presence or absence of a specific DNA sequence
Collections of smaller probes, each of which binds to a different sequence along the length of a given chromosome. Using multiple probes labeled with a mixture of different fluorescent dyes, such that each chromosome has its own unique color. The resulting full-color map of the chromosome
What does karyotype not detect?
Small structural abnormalities
Small sequence variants (INDELS and SNPs)
Copy neutral LOH (like uniparental disomy)
Spectral Karyotyping (SKY)
- Detected with FISH
- Non-targeted approach
- Great to detect inter-chromosomal aberrations - complex chromosome rearrangements, translocations, large INDELS)
What does FISH– Utility detect?
Changes in the number of chromosomes
Large (>500 Kb-2 Mb) insertions or deletions, and translocations
Useful to look at mosaicism
What does FISH– Utility not detect?
Small structural abnormalities (< 500Kb)
(Inversion)
Small sequence variants (INDELS and SNPs)
Copy neutral LOH (like uniparental disomy)
Microarray (oligo array)
From multiple cells
a ton of fish experiments at one
resolution
on the number of probes used and their distribution through the genome – you only see regions represented in the array
What does a “normal” array result mean?
No losses or gains of currently known clinical significance
Does not rule out mosaicism
Does not rule out areas of the genome not covered by the array design
Does not rule out variants that do not result in losses or gains of material (copy neutral LOH and balanced rearrangements, as well as small sequence variants like INDELS and SNPs)
What will Oligo array- alpha GCH-utility detect?
Changes in the number of chromosomes
Relatively small (as small as 1Kb) insertions or deletions
(Unbalanced translocations
What will Oligo array- alpha GCH-utility will not detect?
Balanced structural abnormalities
Inversion
Small sequence variants (INDELS and SNPs)
Copy neutral LOH (like uniparental disomy)
What acan Single Nucleotide Polymorphisms and Oligo Array detect?
Changes in the number of chromosomes
Relatively small (as small as 1Kb) insertions or deletions
Copy neutral LOH (like uniparental disomy)
(Unbalanced translocations)
What Single Nucleotide Polymorphisms and Oligo Array will not detect?
Balanced structural abnormalities
Inversion
Very small sequence variants (except the SNPs on the array!)
What type of assays are good at detecting Chromosomal mosaicism
FISH (it’s fast and easy)
Karyotype (it’s possible but labor intensive)
Oligo + SNP arrays (header to detect unless you have a lot of cells with the missing chromosome because you combine cell samples)
Chromosomal mosaicism
use FISH on a large number of cells (>200) in multiple tissues
Microdeletions
FISH if possible
CMA (Chromosomal microarray) may not detect mosaicism less than 20-25
Small sequence changes
use sequencing (Sanger or NGS on multiple tissues)
