Test2: Lect 11 Susan Olson Flashcards
Resolution of standard karyotyping:
Haploid genome
Whole genome
Routine banding vs high res banding:
- Difference?
- Resolution?
- Done how?
- Difference? Routine banding: during Metaphase (chromosomes are more condensed) During prophase, chromosomes are longer - Resolution? About 5x better in high res. range of millions of BPs - Done how? G-banded chromosome staining
FISH analysis:
- Resolution?
- Resolution?
50 - 250,000 bp
Chromosomal microarrays:
- Resolution?
- Resolution?
50 - 250,000 bp
Whole genome sequencing
- Resolution?
- Resolution?
1 - 1000 bp
Metacentric:
Acrocentric:
telocentric:
centromere in middle
between middle and end
centromere at the end of chromosome
Triploidy:
- Caused by fertilization with two sperm
- Lethal
Aneuploidy:
1 extra or 1 missing chromosome
Down syndrome:
- Type of aneuploidy:
- Most common cause:
- How can someone be a carrier?
- Type of aneuploidy:
Trisomy 21 - Most common cause:
Non disjunction in meiosis 1 or 2 - How can someone be a carrier?
They can have 1 copy of chromosome 21, which is actually two copies of 21 fused to each other.
There is no way for separation to occur, so essentially there will always be non-disjunction at meiosis 1
At what age does aneuploidy risk sky rocket?
Age 35 for women
Turner syndrome:
1 X chromosome
Klinefelter syndrome:
XXY
How could you test to see if you have a large scale chromosomal deletion syndrome like 4P?
G-banded chromosome staining, possibly with high resolution.
Fish would be another possibility
Large scale translocation between two chromosomes:
- Phenotype:
- Ability to have children?
- Phenotype:
They will be normal - Ability to have children?
Quadrivalent chromosome alignment, can result in normal child or abnormal or abortion.
Pericentric inversion vs paracentric:
Pericentric inversion which includes the centromere
Paracentric inversion which does not.
- What happens when you have an odd number of crossing over events?
Pericentric:
- What happens when you have an odd number of crossing over events?
For ABCD x ACBD 1 : 4 normal ABCD 1 : 4 Deletion A duplication D DCBD 1 : 4 Deletion D duplication D ABCA 1 : 4 Inverted still ACBD
Paracentric inversion:
- What happens when you have an odd number of crossing over events?
Usually the chromosome is inviable. You cannot pass this chromosome on.
Isochromosome:
- Define:
- Example:
- Define: Mutation where the arms of the chromosome are mirror images of each other. - Example: ABC (centromere) CBA Turner Syndrome
X chromosome translocation:
A portion of the X chromosome can translocate to another chromosome. If it is does and the person is female then inactivation of that X will inactivate the chromosome it is on as well
Chromosomal mosaicism:
- Define:
- Issue with prenatal screen testing:
- Define:
Some point post zygote a cell gains aneuploidy of chromosome. Its progeny are aneuploid as well - Issue with prenatal screen testing:
Prenatal screening tests placenta, which is made by uterus, with mosaicism there could be aneuploidy in the fetus or in the placenta or in both or in neither. If it is in the placenta and not the fetus then there will be a false positive.
Suppose you have trisomy 21, 2 from your mom one from your dad. But one chromosome is lost, ‘fixing it’. What could still go wrong?
If i lost either of the maternal chromosomes then I still have the right amount of paternal and maternal. Because of imprinting, if I lose my only paternal, some genes will not be expressed within me, and some genes will be overexpressed.
Uniparental disomy:
- Define:
- Identification?
- Define:
Two copies of the same chromosome from one parent. Over-express maternal or paternal genes, do not express the others. - Identification?
G-banded chromosome staining (Dark regions will be heterochromatin, if the gene is being differentially expressed it is likely there is differential patterns of heterochromatin as well)
HETERODISOMY:
parent passes on one copy of each homolog (non-disjunction in meiosis I)
ISODISOMY:
parent passes on two copies of the same chromosome (non-disjunction in meiosis II)
Cancer and chromosomal abnormalities:
- Types:
- Types: Balanced chromosomal rearangements (translocation (no loss of material) Chromosomal imbalances (deletion or duplication)
How can balanced chromosomal rearrangements cause cancer?
2 ways:
- rearrangement lands in a new regulatory environment, and differential expression causes cancer
- rearrangement lands in a an important element, disrupts it
- rearrangement results in a new protein product
Philadelphia Rearrangement:
- define:
- BCR/ABL Fusion by Interphase FISH:
- define:
Switch between chromosome 9 and 22, results in aberrant protein, causes cancer. - BCR/ABL Fusion by Interphase FISH:
This fusion is what causes the increased risk for cancer.
Normal signal pattern = 2 red/ 2 green
Fusion signal pattern = 1 red/ 1 green/ 2 yellow
FISH:
- Define:
- common uses:
- Define:
DNA probe, labelled fluorescent, binds to and marks if the probe sequence is present. - common uses:
1. Absence of hybridization may uncover submicroscopic deletion
2. Used when there is a question of a deletion based on family history or suspicious-looking karyotype.
3. Used to map specific genes or arbitrary sequences to a chromosome region.
4. Used for rapid detection of abnormal chromosome number (interphase)
Which chromosomes can survive trisomy?
13, 18, 21 and X chromosome
Ring chromosome:
Seen more often in cancer
Interphase FISH Analysis:
- Uses?
- Uses?
Monitoring BCR/ABL Fusion by Interphase FISH
Rapid trisomy screening
Chromosome Paints
- Broad:
- Specific:
- Broad:
1. Cocktail of genome or chromosome-specific probes.
2. Delineation of chromosome rearrangements.
3. Chromosome/marker identification - Specific:
1: Color all human chromosomes one color, all mice another
2: color two chromosomes different colors, so you can check if they’ve fused more easily
Multicolor FISH (M-FISH) and Spectral Karyotyping (SKY):
Gives every chromosome its own color
Array Comparative Genomic Hybridization:
- Define:
- Define:
1: Like giant fish assay, but probes are attached to a chip. SNPs are what is being identified.
2: Add your patients DNA labelled green and control DNA labelled red
3: yellow wells are normal. Red wells suggest a deletion. Green wells suggest a duplication
Non-allelic Homologous Recombination (NAHR) can cause:
duplication and deletion
