Genetics 1

Question 1

What is a malformation?

Answer 1

A morphological defect of an organ or part of the body caused by an intrinsically abnormal development process.

Question 2

What is a disruption?

Answer 2

An extrinsic breakdown or interference with an originally normal developmental process.

Question 3

What is a deformation?

Answer 3

Caused by mechanical factors and can normally be fixed with surgery.

Question 4

What is dysplasia?

Answer 4

Abnormal organisation of cells into tissues. Caused by a single gene defect and is prone to a high recurrence risk.

Question 5

What is a sequence?

Answer 5

A pattern of multiple abnormalities derived from a single known anomaly or mechanical factor.

Question 6

What is a syndrome?

Answer 6

Multiple abnormalities that are thought to be pathologically related and not representing a sequence.

Question 7

What is an association?

Answer 7

Non-random occurrence in two or more individuals. Cause is typically unknown.

Question 8

What are the three types of chromosomal abnormalities? Give examples.

Answer 8

Structural - deletions, translocations or insertions
Numerical - aneuploidy
Mosaicism - caused by mitotic non-disjunction

Question 9

What is robertsonian translocation?

Answer 9

Chromosome breaks at centromeres and the two long arms fuse together to form one long chromosome with a single centromere.

Question 10

What is aneuploidy?

Answer 10

Loss or gain of one or more chromosomes.

Question 11

What is monosomy?

Answer 11

The loss of one chromosome. Almost always lethal.

Question 12

Example of monosomy?

Answer 12

Turners syndrome (X)

Question 13

Symptoms of Turners syndrome?

Answer 13

• Webbed neck
• Aortic defects
• Urinary defects
• Short stature

Question 14

How is Turners syndrome treated?

Answer 14

Growth hormone and oestrogen replacement.

Question 15

What is trisomy?

Answer 15

Gain of one chromosome. Can be tolerated on certain chromosomes.

Question 16

Give three examples of trisomy.

Answer 16

• Trisomy 13: Patay syndrome
• Trisomy 18: Edwards syndrome
• Trisomy 21: Down syndrome

Question 17

Symptoms of Patay syndrome?

Answer 17

• Heart defects
• Mental retardation
• Cleft palate

Question 18

Symptoms of Edwards syndrome?

Answer 18

• Heart defects
• Kidney malformation
• Digestive tract defects
• Mental retardation

Question 19

Symptoms of Down syndrome?

Answer 19

• Craniofacial defects (small ears and epicanthic folds)
• Short stature
• Cardiac defects
• Mental retardation
• Limb defects (sandal toe gap)

Question 20

What is tetrasomy?

Answer 20

Gain of two chromosomes. Can be tolerated on some chromosomes.

Question 21

What is an example of tetrasomy?

Answer 21

Klinefelter’s syndrome (XXY)

Question 22

Symptoms of Klinefelter’s syndrome?

Answer 22

• Taller than average
• Infertility
• Phenotypically male
• Learning disabilities (IQ of 80-90)

Question 23

What are the rare variants of Klinefelter’s syndrome?

Answer 23

XXXY and XXXXY

Question 24

What is dosage compensation?

Answer 24

Mechanism that ensures equivalent gene expression between males and females.

Question 25

What three mechanisms are used in dosage compensation?

Answer 25

1) Inactivation of the X chromosome in females 2) Increased gene expression of the X chromosome in males 3) Decreased expression of both X chromosomes in hermaphrodites

Question 26

What is Di George syndrome and its symptoms?

Answer 26

- Caused by a micro deletion - Cardiac defects - Thymic hypoplasia - Cleft palate - Hypokalaemia

Question 27

What is Marie-Charcot-Tooth disease and its symptoms?

Answer 27

- Caused by a micro duplication - Muscular weakness and foot drop - Demyelination of peripheral nerves in adolescence, leading to absent reflexes, slow conduction and lack of sensation in lower limbs

Question 28

How is MCTDT1A treated?

Answer 28

Physiotherapy and corrective surgery

Question 29

What are chromosomes stained with to see the banding?

Answer 29

Giemsa

Question 30

Which arm of the chromosome is smaller.

Answer 30

P arm

Question 31

What is the advantages of next generation sequencing?

Answer 31

- Increased sequencing volume (can sequence millions of DNA fragments simultaneously) - Greater sensitivity to rare variants

Question 32

How does Sanger/NGS sequencing work?

Answer 32

Fluorescent DNA polymerase adds nucleotides onto a growing template DNA strand.

Question 33

What is copy number variation?

Answer 33

When the number of copies of a particular gene varies between individuals.

Question 34

What are the implications of copy number variations?

Answer 34

Some cancers (breast cancer) are associated with increased copy numbers of particular genes whilst other disorders are associated with deletions (Prader-Willi and Angelman syndrome).

Question 35

Give example of a mutation in the same gene causing different disorder.

Answer 35

Cystic fibrosis and CAVD (congenital absence of the Vas Deferens)

Question 36

Give an example of the same disease caused by a different gene.

Answer 36

Haemophillia (F8 and F9 gene on X chromosome)

Question 37

Give an example of a disorder with two different patterns of inheritance.

Answer 37

Epidermolysis bullosa (autosomal recessive or dominant)