Autosomal Recessive Disorders

Question 1

Give an example of a common technique used to visualise chromosomes.

Answer 1

Giemsa dye staining with light microscopy.

Question 2

List 6 autosomal recessive disorders.

Answer 2

1 - Cystic fibrosis.

2 - Recessive mental retardation.

3 - Congenital deafness.

4 - Phenylketonuria (many metabolic errors).

Question 3

List 6 signs of cystic fibrosis.

Answer 3

1 - Chronic lung disease (secondary to recurrent infection).

2 - Secondary cardiac failure.

3 - Impaired pancreatic function.

4 - Diabetes.

5 - Cirrhosis.

6 - Male infertility.

Question 4

Which gene is affected with cystic fibrosis?

Answer 4

The cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Question 5

What is spinal muscular atrophy?

Describe the pathophysiology.

Answer 5

• An autosomal recessive condition causing wasting and weakness of proximal muscles.
• Caused by degeneration of the cell bodies of motor neurones in the spinal cord.

Question 6

Which gene is affected with spinal muscular atrophy?

Answer 6

The survival motor neurone (SMN) gene.

Question 7

What is the function of the SMN gene?

Answer 7

To control RNA processing.

Question 8

What is a Mendelian trait?

Answer 8

A trait that is controlled by a single locus.

Question 9

Give an example of a non-Mendelian trait.

Answer 9

Sensorineural deafness.

Question 10

Why might two parents that are homozygous for an autosomal recessive disorder not produce offspring that have the phenotype for that disorder?

Answer 10

It may be a non-Mendelian trait.

Question 11

What is pseudodominance?

What causes it?

Answer 11

• When a recessive trait mimics the inheritance of a dominant trait.
• E.g. males only have one of each sex chromosome so only need one recessive allele to express the trait.
• Could also happen in autosomal recessive traits if the other allele is deleted or mutated.

Question 12

What is the Hardy-Weinberg equation?

Answer 12

q^2 + p^2 + 2pq = 1

e. g. q^2 is aa, p^2 is AA, 2pq is Aa or aA.
* For an autosomal recessive condition, frequency of affected individuals = q^2.

Question 13

What is the main assumption of the Hardy-Weinberg equation?

What must be true for this assumption to be valid?

Answer 13

• That the relative proportions of each genotype remain constant in subsequent generations. Only true if ther is:

1 - Random mating.

2 - An infinitely large population.

3 - No preferential selection of genotypes.

4 - No new alleles.

Question 14

How does the risk of having offspring with an autosomal recessive disorder change where the parents are first cousins?

Answer 14

Increases from 2% (normal) to 5%.

Question 15

List 2 examples of deleterious conditions that convey an advantage.

Answer 15

1 - Sickle cell disease increases resistance to malaria.

2 - Cystic fibrosis increases resistance to typhoid.

Question 16

How does cystic fibrosis increase resistance to typhoid?

Answer 16

Salmonella typhi requires the unmutated Cl- channel to enter epithelial cells.

Question 17

How does sickle cell disease increase resistance to malaria?

Answer 17

Red blood cells of heterozygotes more effectively express malarial antigens.

Question 18

Define penetrance.

Answer 18

The extent to which a gene is expressed in individuals who are carriers, measured by the proportion of carriers showing the characteristic phenotype.

Question 19

What is a segregation analysis?

Answer 19

A study of how a disorder is inherited in families, used to establish the mode of inheritance.

Question 20

How would a segregation analysis for an autosomal dominant disease be carried out?

Answer 20

By comparing the number of affected offspring born to affected parents (likely to be high).