Genetics

Question 1

What is the inheritance pattern of autosomal dominant diseases?

Answer 1

Both homozygotes and heterozygotes manifest disease

There is no carrier state in autosomal dominant diseases.

Question 2

In autosomal dominant inheritance, what percentage of children will inherit the disease from an affected parent?

Answer 2

50%

This applies to each child regardless of the parent’s sex.

Question 3

Are both males and females affected in autosomal dominant diseases?

Answer 3

Yes

Question 4

What is non-penetrance in the context of genetic diseases?

Answer 4

Lack of clinical signs and symptoms despite the presence of an abnormal gene

Example: 40% of individuals with otosclerosis may show no symptoms.

Question 5

What is a spontaneous mutation in genetics?

Answer 5

A new mutation occurring in one of the gametes

Example: 80% of individuals with achondroplasia have unaffected parents.

Question 6

List three examples of autosomal dominant conditions.

Answer 6

• Achondroplasia
• Huntington’s disease
• Marfan’s syndrome

Question 7

What is the inheritance pattern of autosomal recessive diseases?

Answer 7

Only homozygotes are affected

Question 8

In autosomal recessive inheritance, what is the chance of two heterozygote parents having an affected child?

Answer 8

25%

They also have a 50% chance of having a carrier child and a 25% chance of having an unaffected child.

Question 9

Are autosomal recessive disorders typically metabolic or structural?

Answer 9

Metabolic

Notable exceptions exist, such as certain structural conditions.

Question 10

List three examples of autosomal recessive conditions.

Answer 10

• Cystic fibrosis
• Sickle cell anaemia
• Wilson’s disease

Question 11

What are the two types of cell division?

Answer 11

Mitosis and meiosis

Question 12

What is the main outcome of mitosis?

Answer 12

2 diploid daughter cells

Question 13

What is the main outcome of meiosis?

Answer 13

4 haploid daughter cells

Question 14

What occurs during the prophase of mitosis?

Answer 14

Chromatin in the nucleus condenses

Question 15

List three key features of Patau syndrome.

Answer 15

• Microcephalic
• Cleft lip/palate
• Polydactyly

Question 16

Which congenital infection is most common in the UK?

Answer 16

Cytomegalovirus

Question 17

What are the characteristic features of congenital rubella syndrome?

Answer 17

• Sensorineural deafness
• Congenital cataracts
• Congenital heart disease

Question 18

What is the risk of inherited defects in consanguineous couples?

Answer 18

Approximately double that of a non-related couple

Question 19

What is the inheritance pattern of Fabry disease?

Answer 19

X-linked recessive

Question 20

What causes homocystinuria?

Answer 20

Deficiency of cystathionine beta synthase

Question 21

What is the hallmark of mitochondrial diseases?

Answer 21

Inheritance only via the maternal line

Question 22

What is the role of the p53 gene?

Answer 22

Tumor suppressor gene that prevents entry into the S phase until DNA is repaired

Question 23

What is penetrance in genetics?

Answer 23

The proportion of individuals with a disease-causing allele who express the related phenotype

Question 24

What is expressivity in genetics?

Answer 24

The extent to which a genotype shows its phenotypic expression in an individual

Question 25

What is phenylketonuria (PKU)?

Answer 25

An autosomal recessive condition caused by a defect in phenylalanine metabolism

Question 26

What is a key feature of McCune-Albright syndrome?

Answer 26

Precocious puberty

Question 27

What are 'red, ragged fibres' indicative of in histology?

Answer 27

Mitochondrial disease

Question 28

How do oncogenes differ from tumor suppressor genes?

Answer 28

Oncogenes promote cancer through gain of function; tumor suppressor genes increase cancer risk through loss of function

Question 29

What is the main enzyme defect in phenylketonuria (PKU)?

Answer 29

Phenylalanine hydroxylase ## Footnote This enzyme converts phenylalanine to tyrosine.

Question 30

What are the high levels of phenylalanine associated with?

Answer 30

Learning difficulties and seizures ## Footnote High phenylalanine can lead to developmental problems.

Question 31

Where is the gene for phenylalanine hydroxylase located?

Answer 31

Chromosome 12

Question 32

What is the incidence of PKU?

Answer 32

1 in 10,000 live births

Question 33

What is a classic feature of a child with PKU?

Answer 33

Fair hair and blue eyes

Question 34

What is the Guthrie test used for?

Answer 34

Diagnosis of PKU and other biochemical disorders ## Footnote It is a 'heel-prick' test done at 5-9 days of life.

Question 35

What does polymerase chain reaction (PCR) require?

Answer 35

Sample DNA, two DNA primers, and a thermostable DNA polymerase (Taq)

Question 36

What is the main advantage of PCR?

Answer 36

Sensitivity; only one strand of sample DNA is needed

Question 37

What does reverse transcriptase PCR amplify?

Answer 37

RNA

Question 38

What genetic disorder is associated with the absence of the active Prader-Willi gene?

Answer 38

Prader-Willi syndrome

Question 39

What are the features of Prader-Willi syndrome?

Answer 39

*Hypotonia during infancy* *Dysmorphic features* *Short stature* *Hypogonadism and infertility* *Learning difficulties* *Childhood obesity* *Behavioural problems in adolescence*

Question 40

What are purines?

Answer 40

Adenine and Guanine ## Footnote Remembered with the mnemonic 'Pure As Gold' (Pur A G).

Question 41

What are pyrimidines?

Answer 41

Cytosine, Uracil, Thymine ## Footnote Remembered with the mnemonic 'Cut Py' (C U T Py).

Question 42

How many hydrogen bonds occur between Guanine and Cytosine?

Answer 42

3 hydrogen bonds

Question 43

How many hydrogen bonds occur between Adenine and Thymine?

Answer 43

2 hydrogen bonds

Question 44

What is the clinical significance of purines and pyrimidines?

Answer 44

Inhibition of their synthesis can inhibit cellular replication and cause cell death

Question 45

What is the salvage pathway in purine synthesis?

Answer 45

Production of purine nucleotides AMP or GMP using free guanine or adenine bases

Question 46

What is the role of HGPRT in purine metabolism?

Answer 46

Recycle guanine and hypoxanthine to GMP and IMP, respectively

Question 47

What condition is caused by a deficiency in HGPRT?

Answer 47

Lesch-Nyhan syndrome

Question 48

What is the final product of purine degradation?

Answer 48

Uric acid

Question 49

What enzyme converts xanthine to uric acid?

Answer 49

Xanthine oxidase

Question 50

What is the consequence of adenosine deaminase (ADA) deficiency?

Answer 50

Severe combined immunodeficiency (SCID)

Question 51

What are trinucleotide repeat disorders?

Answer 51

Genetic conditions caused by an abnormal number of repeats of a sequence of three nucleotides

Question 52

What phenomenon describes earlier age of onset in successive generations of trinucleotide repeat disorders?

Answer 52

Anticipation

Question 53

What is an example of a tumor suppressor gene?

Answer 53

p53

Question 54

What is the inheritance pattern of Turner's syndrome?

Answer 54

Chromosomal disorder affecting females

Question 55

What is a common feature of Turner's syndrome?

Answer 55

Short stature

Question 56

What are the long-term health risks associated with Turner's syndrome?

Answer 56

*Aortic dilatation* *Dissection*

Question 57

What is William's syndrome caused by?

Answer 57

Microdeletion on chromosome 7

Question 58

What are the features of William's syndrome?

Answer 58

*Elfin-like facies* *Friendly and social demeanor* *Learning difficulties* *Short stature*

Question 59

What type of inheritance do X-linked dominant conditions follow?

Answer 59

X-linked dominant fashion

Question 60

What is a key characteristic of X-linked recessive inheritance?

Answer 60

Only males are affected

Question 61

What is an exception to male-only X-linked recessive conditions?

Answer 61

Turner's syndrome

Question 62

What are some examples of X-linked recessive conditions?

Answer 62

*Duchenne muscular dystrophy* *Haemophilia A* *Fabry's disease* *G6PD deficiency*