Session 16: Chromosome Abnormalities, Cytogenetics Flashcards by Emily Wilson

What are some reasons for referral to a cytogeneticist?

Prenatal diagnosis
Birth defects
Abnormal sexual development
Infertility

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What two methods can be used for prenatal diagnosis methods?

Chorionic Villus Sampling (CVS) (Sample from villi of chorion)
Amniocentesis (Sample from amniotic fluid)

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Is there a slightly greater risk of miscarriage in using CVS or amniocentesis in prenatal diagnosis?

CVS

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What is polyploidy?

When cells gain a whole set of chromosomes (i.e. 3n) which is usually the result of polyspermy

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What is aneuploidy?

The loss or gain of individual chromosomes, resulting in abnormal chromosome number

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How does aneuploidy arise?

From meiotic non-disjunction, when one or more homologous chromosomes fail to separate at anaphase resulting in abnormal distribution (monosomy or trisomy)

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If non-disjunction occurs during meiosis I, what will be the outcome for the gametes?

They will all have chromosomal abnormalities
50% monosomy
50% trisomy

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If non-disjunction occurs during meiosis II, what will be the outcome for the gametes?

Half of the gametes will be “normal”
Half of the gametes will be abnormal: 25% monosomy
25% trisomy

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If non- disjunction occurs during mitosis, what will be the outcome for the gametes?

They will have mosaicism: populations of somatic cells will be composed of cells that are genetically different to others

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What are the pseudoautosomal regions?

What happens to these during meiosis?

PAR1 (terminal region of q arm)
PAR2 (terminal region of p arm)
They pair and recombine during meiosis

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Can an individual have monozomy and be viable?

Yes, usually not viable but can be in Turner syndrome

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What is the SRY?

A region on the Y chromosome that lines up with an X chromosome during meiosis

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What are the two types of translocation?

Reciprocal

Robersonian

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What types of reciprocal translocation are there?

Alternate (balanced) 
Adjacent 1 (unbalanced) 
Adjacent 2 (unbalanced) 
3:1 non disjunction (unbalanced)
4:0 non disjunction (unbalanced)

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Does reciprocal translocation occur during meiosis I or meiosis II? Why?

Meiosis I- this is when crossing over occurs

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During meiosis I, chromosomes form what, which then segregates to give unbalanced or balanced arrangements of chromosomes?

A quadrivalent

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What is a Robertsonian Translocation?

When the long arms of two acrocentric chromosomes fuse together at a common centromere

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What does Robersonian translocation lead to?

Either monosomy or trisomy

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What three events can lead to aneuploidy?

Non-disjunction
Anaphase lag
Robertsonian translocation

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What can FISH be used to identify?

Microdeletions/duplications
To identify chromosome of origin
To identify individual chromosomes in arrangement

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What can aCGH be used to detect?

Unbalanced translocations

Is adjacent 1 or adjacent 2 segregation more common?

Adjacent 1

Adjacent 2 is very very rare and is not really seen in live newborns

Will an individual with a 47, XXY karyotype have affected siblings?

No, it is unlikely as the gametes from the parent are unlikely to have the same fault during meiosis again

What is non-invasive prenatal testing (NIPT)?

Prenatal testing that involves taking a blood sample from the mother and does not require a sample to be taken directly from the pregnancy

What can NIPT currently be used to look for?

Downs syndrome Fetal sex Single gene disorders

What can NIPT not be currently used to detect? | Why?

Chromosomal translocations | Need to be able to grow cell and get them in metaphase to determine this

If a man has a Robertsonian 21;21 translocation karyotype, will he be clinically normal? Will his children be abnormal?

Yes he will be clinically normal | He can only father embryos wth trisomy 21 or monosomy 21

Non-disjunction in one of the early mitotic divisions of the zygote will result in what?

Chromosomal mosaics

Why can Array Comparative Genome Hybridisation (aCGH) not be used to detect balanced rearrangements?

aCGH is used to assess gene content and therefore will not give us additional information about balanced rearrangements as the rearrangement contains the same amount of genetic information

Which cohort of patients, who require cytogenetic investigation would you expect to have a balanced rearrangement?

Patients who have been trying to conceive but have not been able to due to the unbalanced translocation in the foetus leading to it not being viable

What test can be used to detect anything phenotypically abnormal a child's development and learning?

aCGH

What would be the preferred investigative technique in a cytogenetic laboratory for a newborn baby with a heart abnormality?

aCGH

What would be the preferred investigative technique in a cytogenetic laboratory for a child with learning difficulties?

aCGH

What would be the preferred investigative technique in a cytogenetic laboratory for a women who was having recurrent miscarriage?

FISH karyotyping

What would be the preferred investigative technique in a cytogenetic laboratory for sperm and egg donation?

FISH karyotyping

What would be the preferred investigative technique in a cytogenetic laboratory for a child with developmental delay and an apparently balanced chromosome inversion that is de novo?

aCGH | We want to know whether it is unbalanced or not and aCGH will tell us that i.e. it will only tell us if it is unbalanced

During what phase of mitosis do chromosomes need to be in order to do chromosome analysis on them?

Metaphase

In a 3:1 reciprocal translocation, what can be seen in tertiary trisomy?

2 normal chromosomes | One derivative

In a 3:1 reciprocal translocation, what can be seen in tertiary monosomy?

One derivative - This is very rare

In a 3:1 reciprocal translocation, what can be seen in interchange trisomy?

2 derivative chromosomes | One normal

What happens during pregnancy if there is a reciprocal translocation involving chromosomes 13, 18 or 21?

The baby may be compatible to survive to term

In a 3:1 reciprocal translocation, what is interchange monosomy?

Where there is one normal chromosome | This has never been seen

What are the advantages of aCGH?

It examines the entire genome at high resolution It is targeted against known genetic conditions and sub telomere regions 1 array is equivalent to many thousands of FISH investigations Can be automated Detailed information on duplicated/deleted regions Better phenotype/genotype correlation

What are the disadvantages of aCGH?

More expensive than karyotyping Will not detect balanced rearrangements Mosaicism may be missed

Deletions and duplications arise through what?

Uneven pairing and recombination during meiosis

Where can deletions and duplications arise?

At the ends of the arms (terminal) | Within the chromosome arm itself (interstitial)

Deletions and duplications always result in balanced or unbalanced?

Unbalanced

Can G banding be used to see microdeletions and microduplications? If not, what would you use instead?

Not always | Would use FISH

Can aCGH be used to detect mutations (nucleotide level)?

No, not sensitive enough to see at this small level

What is uniparental disomy (UPD)?

Presence of two chromosomes from one parent | i.e. two chromosomes from one parent rather than one from each

What is meant by idodisomy? | At what stage of meiosis does this occur?

The presence of two identical chromosomes from one parent | Meiosis II

What is meant by heterodisomy? | At what stage of meiosis does this occur?

The presence of two homologous chromosomes from one parent | Meiosis I