18. Chromosome Abnormalities Flashcards Preview

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Flashcards in 18. Chromosome Abnormalities Deck (50)
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1
Q

How is DNA packaged?

A

Wrapped round an octamer of histones. 166 base pairs per octamer and histone H1 stabilises. Higher order structures are then stabilised by hanging loops of DNA on a protein scaffold - chromatin.

2
Q

What form of chromatin is active for genes to be expressed?

A

Euchromatin is the active form.

3
Q

How does chromatin switch between its active and inactive forms?

A

By epigenetic modification. Activates by methylation and deactivated by demethylation.

4
Q

What does chromosome analysis require?

A

A source of living cells for in vitro growth. The cells are cultures, accumulated at metaphase and harvested.

5
Q

Which samples are cultures in suspension and which are grown on substrate from the following?

a. Bone marrow
b. Amniotic fluid
c. CVS
d. Solid tissue
e. Blood

A

a. Suspension
b. Substrate
c. Substrate
d. Substrate
e. Suspension.

6
Q

What is karyotyping?

A

The systematic sorting of chromosomes.

7
Q

What do the following mean?

a. Metacentric
b. Sub-metacentric
c. Acrocentric.

A

a. The p and q arms of the chromosome are of equal length and the centromere is in the middle.
b. The p arm is shorter than the q arm as the centromere is nearer the top/ p arm.
c. The p is very short and has no euchromatin material in it so no genes of importance. The q arm is far longer.

8
Q

How are chromosomes grouped?

A

By size (in increasing size) and groups A-G by shape.

9
Q

How are G-band chromosomes dyed?

A

Metaphases exposed to trypsin, which digests proteins. Stained with Romanowski type dye. This produces dark G positive bands (AT rich and gene poor) and light G negative bands (GC rich and gene rich).

10
Q

How does automated karyotyping work?

A

The slides are scanned automatically by a microscope and images are taken. Digital karyotypes are made from the images. The chromosomes are paired up on the screen fro analysis.

11
Q

What is a problem with automated karyotyping?

A

It is very expensive.

12
Q

What details are given on a chromosome report?

A

The chromosome number, sex complement and structural changes.

13
Q

How would the following chromosomal information be written in ISCN form?
A normal female with trisomy 21.

A

47,XX,+21

14
Q

What does the following mean in words from the ISCN form?

46,XY,inv(7),(p11.2q11.23)

A

A male with a chromosome 7 inversion at the break points 11.2 on the short, p arm and 11.23 on the long, q arm.

15
Q

What are some uses of cytogenic analysis?

A

For accurate diagnosis/prognosis of clinical problems (identifies the syndrome, accounts for phenotype and pregnancy loss), for better clinical management, to assess future reproductive risks and for prenatal diagnosis.

16
Q

Give brief details of chorionic villus sampling.

A

11-12 weeks gestation, 1.2% risk of miscarriage, under ultrasound guidance to minimise this risk.

17
Q

Give brief details of amniocentesis.

A

15 weeks + gestation. 0.8% risk of miscarriage, under ultrasound guidance to minimise this risk.

18
Q

How is Down syndrome screened for prenatally?

A

Maternal serum screening, first trimester screening, family history abnormality, ultrasound scan and DNA studies.

19
Q

What is Williams syndrome cause by?

A

Deletion 7q11.23.

20
Q

What does a deletion at 22q11.2 cause?

A

DiGeorge syndrome - heartflow defects.

21
Q

Define aneuploidy.

A

Loss or gain of whole chromosomes.

22
Q

What causes aneuploidy?

A

Errors at cell division in meiosis. Non-disjunction at one of the meiotic cell divisions so forms gametes with a missing chromosome (monosomy) and an extra chromosome (trisomy). Or in mitotic cell division this causes mosaicism, two cell populations in an individual.

23
Q

What three trisomies are viable?

A

Down syndrome +21, Patau syndrome +13 and Edwards +18.

24
Q

What monosomy is viable?

A

Turner syndrome, 45X.

25
Q

What is polyploidy?

A

The gain of a whole haploid set of chromosomes. Triploidy 3n, 69XXX.

26
Q

What causes polyploidy?

A

Polyspermy most commonly, the egg is fertilised by more than one sperm.

27
Q

What is anaphase lag?

A

Chromosomes are left behind at cell division because of defects in spindle function or attachment to chromosomes. The chromosome may be lost entirely in mitosis or meiosis.

28
Q

What are the clinical features of Down syndrome (trisomy 21)?

A

Hypotonia (floppy baby - low muscle tone), characteristic facial features, heart defects, intellectual disability.

29
Q

What is the frequency of Down syndrome?

A

1:650-1000

30
Q

What are the clinical features of Edwards syndrome (trisomy 18)?

A

Small lower jaw, prominent occiput, low-set ears, rocker bottom feet, overlapping fingers.

31
Q

What is the frequency of Edwards syndrome?

A

1:6000, with female predominance.

32
Q

What is the modal lifespan of Edwards syndrome?

A

5-15 days.

33
Q

What are the clinical features of Patau syndrome (trisomy 13)

A

Multiple congenital abnormalities, polydactyl, holoprosencephaly.

34
Q

What is the incidence of Patau syndrome?

A

1:12000

35
Q

What is the lifespan of Patau syndrome?

A

Majority die in neonatal period (first four weeks after delivery).

36
Q

What are the clinical features of Turner syndrome (45,X)?

A

Short stature, heart defects, mild learning difficulties, infertility, puffy feet and redundant skin at the back of the neck.

37
Q

What causes Turner syndrome?

A

Absent paternal X.

38
Q

What is the incidence of Turner syndrome?

A

1:2500

39
Q

What is X inactivation?

A

Only one X chromosome is ever active in a human cell, in a female, they have two X chromosomes. X inactivation ensures individual have the same X chromosome complement that is active.

40
Q

Why is single X activation a problem?

A

Males only have one X chromosome but the X and Y chromosomes have short regions in common at the tips of the p and q arms. The PAR1 and PAR2 regions are essential for meiosis pairing.

41
Q

What is mosaicism?

A

Presence of two or more cell lines in an individual, normally from mitotic non-disjunction.

42
Q

What is uniparental disomy?

A

The presence of homologous chromosomes from one parent.

43
Q

Define isodisomy.

A

2 identical chromosomes from one parent.

44
Q

Define heterodisomy.

A

2 homologous chromosomes from one parent.

45
Q

What is segmental uniparental disomy?

A

Only part of the chromosome is involved.

46
Q

Why is uniparental disomy a problem?

A

When it comes to imprinting. Imprinted chromosomes show differential expression of specific genes depending on their parental origin.

47
Q

What are two UPD syndromes?

A

Prader-Willi/Angelman syndrome (15) and Russell-Silver/Beckwith-Wiedemann (11).

48
Q

What are the four origins of UPD?

A

Trisomy rescue (commonest), monosomy rescue, gamete complementation and mitotic error.

49
Q

Explain how trisomy rescue can lead to UPD.

A

A disomic and monosomic gamete form a trisomic conceptus. In postzygotic mitosis, a mitotic error means the monosomic gamete part is removed, leaving all the genetic material from the disomic gamete, hence the UPD embryo.

50
Q

How can UPD be tested for?

A

Molecular genetic testing, see whether inheritance is biparental - if not UPD is confirmed.