Genetics

Question 1

What is a Robertsonian Translocation?

Answer 1

Where chromosomes break at their centromeres and the long arms fuse to form a single large chromosome.

Question 2

Define deformation.

Answer 2

Distortion of a structure by mechanical force.

Question 3

Define dysplasia.

Answer 3

Abnormal organisation of tissue. Pre-cancerous cells which show the genetic and cytological features of malignancy but not invading the underlying tissue.

Question 4

What is genetic imprinting?

Answer 4

Where genes are expressed differently according to whether they’re inherited on the maternal or paternal chromosome.

Question 5

What weeks of gestation are each trimester?

Answer 5

1st = 1-12
2nd = 13-26
3rd = 27-40

Question 6

What are the purposes of the 12 week scan?

Answer 6

Date the pregnancy accurately
Diagnose multiple pregnancy
Diagnose major foetal abnormalities
Diagnose early miscarriage
Assess DS risk and other chromosomal abnormalities

Question 7

What is nuchal translucency?

Answer 7

Thickness of the fluid at the back of the foetal neck.

Question 8

How is nuchal translucency used in diagnosis.

Answer 8

Should be <3mm

>3mm indicates DS, Patau, Turner’s, Edward’s.

Question 9

What are the routine ultrasound scans in a pregnancy?

Answer 9

Nuchal scan - 10-14 weeks

Mid-trimester anomaly scan - 20-22 weeks

Question 10

When can cell-free foetal DNA (cffDNA) be detected in the maternal plasma?

Answer 10

First detectable after 4-5 weeks gestation. Accurate detection after 9 weeks gestation.

Question 11

How can cffDNA be used to diagnose aneuploidy conditions?

Answer 11

Amount of cffDNA for particular chromosomes will be more/less than expected. E.g. for trisomy 21, more chromosome 21 detected than expected.

Question 12

How can cffDNA be used to assess risk of x-linked conditions.

Answer 12

SRY gene detected enabling determination of sex. If female, no risk.

Question 13

Discuss limitations of cffDNA as a technique.

Answer 13

In multiple pregnancies, not possible to tell which foetus DNA is from.
In women with high BMI, cffDNA reduced.

Question 14

What is chorionic villus sampling (CVS)?

Answer 14

An invasive transabdominal/transvaginal technique where a sample of the chorionic villi is taken. Chorionic villi = part of the developing placenta: have the same DNA as the foetus. Test can be conducted from 11-14 weeks. 1-2% miscarriage risk.

Question 15

What is an amniocentesis test?

Answer 15

A sample of the amniotic fluid (which contains foetal cells) is taken. Test can be conducted from 16 weeks. 1% miscarriage risk.

Question 16

What does PGD stand for?

Answer 16

Pre-implantation Genetic Diagnosis.

Question 17

What is a single nucleotide polymorphism (SNP)?

Answer 17

A mutation present in at least 1% of the population.

Question 18

What is cystic fibrosis and how is it caused?

Answer 18

It is a monogenic autosomal recessive disease caused by mutations in the CFTR gene. This mutation affects the chloride ion channels, leading to excessive mucous production in airways and pancreas, affecting breathing and secretion of pancreatic enzymes.

Question 19

Define penetrance.

Answer 19

The proportion of individuals of a population with a specific allele that also have the expected phenotype (they express the associated trait).

Question 20

Define variable expressivity.

Answer 20

Phenotype expressed to a different degree in individuals with the same genotype.

Question 21

Define consanguinity.

Answer 21

Inbreeding between 2nd cousins or closer.

Question 22

What are obligate carriers.

Answer 22

Clinically unaffected people who carry a gene mutation based on their family history (autosomal recessive or x-linked).

Question 23

What is the difference between the proband and the consultand?

Answer 23

The proband is the first affected family member who seeks medical attention for a genetic disorder
The consultand is the person about whose future offspring the genetic counsellor is about to make predictions.

Question 24

What is the difference between anaphase in mitosis and anaphase I in meiosis?

Answer 24

In mitosis, the SISTER CHROMATIDS are pulled apart.

In meiosis, the HOMOLOGOUS PAIRS are pulled apart.

Question 25

Why do chromosomes appear banded in karyotypes?

Answer 25

The Giemsa dye stains regions with lots of adenine and thymine base pairs.

Question 26

Give features of a Down’s syndrome person.

Answer 26

Flat nasal ridge, epicanthic folds, low set ears, single palmar crease, enlarged gap between hallux and 2nd toe, hypotonia, developmental delay, congenital heart defects.

Question 27

Which aneuploidy causes Edward’s Syndrome?

Answer 27

Trisomy 18 (47,XY/XX,+18)

Question 28

Give features of Edward’s Syndrome

Answer 28

Low birth weight, low set ears, small facial features, clenched hand with overlapping fingers, congenital heart defect, developmental delay. Most foetuses die: those who survive to infancy experience severe defects and typically die shortly after.

Question 29

Which aneuploidy causes Klinefelter’s Syndrome?

Answer 29

Sex chromosome trisomy: XXY

Question 30

Give features of Klinefelter’s syndrome.

Answer 30

Males: infertility (small firm testes), loss of secondary sexual characteristics - reduced facial and pubic hair, tall, long legs, narrow shoulders, wide hips, gynaecomastia.

Question 31

Which syndrome is caused by a sex chromosome monosomy, X0?

Answer 31

Turner syndrome.

Question 32

Give features of turner syndrome.

Answer 32

Females: infertility, short stature, webbed neck, broad chest. Behavioural problems, sensorineural deafness, recurrent ear infections.

Question 33

Which chromosomes are acrocentric?

Answer 33

13, 14, 15, 21, 22

Question 34

Define non-disjunction

Answer 34

The failure of homologous chromosomes or sister chromatids to separate properly during meiosis.

Question 35

What is uniparental disomy and name a condition which can be caused by it.

Answer 35

Where 2 copies of a chromosome are inherited from one parent are 0 from the other are inherited. Can cause Angelman’s syndrome and Prader Willi syndrome.

Question 36

What is phenylketonuria?

Answer 36

A deficiency in phenylalanine hydroxylase meaning phenylalanine can’t be broken down and builds up in the brain and blood.

Question 37

What is leptin?

Answer 37

A hormone made by adipocytes which circulates at levels proportional to the amount of adipose tissue.
Acts on hypothalamus to inhibit appetite.
LOW when LOW body fat
HIGH when HIGH body fat

Question 38

Describe the most common mutation responsible for cystic fibrosis.

Answer 38

Delta F508.
Deletion of 3 nucleotides = loss of phenylalanine at 508th position of protein.
CFTR protein doesn’t fold normally and is degraded.

Question 39

What are Prader-Willi and Angelman syndromes caused by?

Answer 39

Lack of gene expression from paternal chromosome 15 and maternal chromosome 15 respectively.

Question 40

Define phenocopy.

Answer 40

Having the same disease but a different underlying cause.

Question 41

Define non-disjunction.

Answer 41

The failure of one or more pairs of homologous chromosomes or sister chromatids to separate during meiosis.