Clinical genetics & Pregnancy 1

Question 1

genetic tests used in pregnancy and tissue sampled?

-gestation & miscarriage risk?

Answer 1

Chorionic villus biopsy-placenta
Amniocentesis-skin/urine cells
Fatal blood sampling-blood
+fetal DNA from mothers serum

-Chorionic villus biopsy: 11.5 wks, 1-2%
Amniocentesis: 16 wks+, 0.5-1%
Fatal blood sampling: 18 wks +, 1-2%
Fetal DNA from maternal blood: 8 wks+, none

Question 2

what is placental Mosiacism?

Answer 2

when tissue with chromosomal abnormalities arises in the placenta but not in the baby, might be anomaly and not affect the whole baby

Question 3

Analysis of samples

• whole genome methods? (4)
• Targeted methods? (3)

Answer 3

-standard Karyotype- in metaphase
Array CGH
whole genome sequencing

-point mutation testing
Fluorescence in-situ Hybridisation (FISH)
Quantitative Fluorescent PCR (QF-PCR)

Question 4

what is a polymorphism?

-difference between mutation and polymorphism?

Answer 4

a genetic variation not necessarily causing disease

-Mutation: 
De-Novo
Bigger
Affects Known gene
Previously reported in same phenotype
Polymorphism:
Normal parent has it
Smaller
“empty” genetic region
Previously reported as polymorphism

Question 5

what is FISH used for?

Answer 5

Counts specific chromosomes in very specific places i.e. looks for deletions but need to know here to look

Question 6

indications for aCGH or chromosome analysis? (3)

Answer 6

high risk of chromosomal trisomy on screening
fetal abnormality on screening
e.g. small size, inc nuchal thickness, structural malformation
parent has balanced chromosomal rearrangement

Question 7

how is sex tested?

-difficulty?

Answer 7

Via non-invasive prenatal testing:
Free fetal DNA in maternal circulation allows sex determination trisomy testing

-Only 10% of the DNA sampled is from the foetus

Question 8

what is used to test for trisomy 21?

Answer 8

Non- invasive prenatal testing, there will be more reads from chromosome 21

Question 9

chromosome changes causing disease:

• balanced chromosome rearrangement?
• unbalanced chromosome rearrangement?

Answer 9

• balanced: All the chromosomal material is present

- Unbalanced: Extra or missing chromosomal material. Usually 1 or 3 copies of some of the genome.

Question 10

define Aneuploidy?

-give 2 examples?

Answer 10

the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46
i.e. too many or too few

-patau syndrome (trisomy 13)
Turner syndrome

Question 11

what is a robertsonian translocation?

-increases risk of what?

Answer 11

when 2 acrocentric chromosomes are stuck end to end

-trisomy in pregnancy

Question 12

give the 4 different types of translocation

Answer 12

robertsonian

reciprocal
(an exchange of material between non homologous chromosomes, might not have a phenotypic effect but gives reproductive risk)

balanced
(an even exchange of material with no genetic information extra or missing, and ideally full functionality)

unbalanced
(where the exchange of chromosome material is unequal resulting in extra or missing genes) can be detected with aCGH

Question 13

what do balanced translocations result in?

Answer 13

miscarriage (large segments)

dysmorphic delayed child