Lecture 17: Autosomal Dom and Rec disorders

Question 1

Pattern of inheritance tracks what

Answer 1

the trait- not the specific mutation. This can be traits because of the disease

Question 2

What rules apply to Autosomal dominant inheritance assuming complete penetrance and no new mutation

Answer 2

1. Both sexes able to be affected and transmit
2. transmission is vertical- if child is affected, one parent must be affected
3. In affected families the ratio of affected children to non affected is usually 1:1
4. Two non affected parents will not produce any affected children

Question 3

People with Autosomal dominant disorders have a … genotype- why. Why does the dominant allele cause disease?

Answer 3

Heterozygous state because homozygous causes natal death

• The reduced amount of protein produced isn’t enough for normal cellular function or
• The abnormal protein produced (often non enzymic and non diffusible) can have a dominant negative effect over the normal protein produced.

Question 4

What causes Achondroplasia and why is a dominant autosomal disorder

Answer 4

Caused by mutation in fibroblast growth factor receptor 3 gene.
The protein produced causes premature differentiation of chondrocytes into bone. The wild type allele cannot compensate for/ reduce the mutant alleles activity so its an autosomal dominant allele.

Question 5

What clinical features characterise Achondroplasia

Answer 5

Shortening of proximal limbs, prominent forehead, depressed nasal bridge and otitis media.

Question 6

The probability of having an affected child for some inherited disorders increases exponentially with… and why in the case of achondroplasia

Answer 6

-Age, for achondroplasia this is because the mutation in FGFR3 in spermatogonia gives them a growth advantage and therefore over time can start being more common in the ejaculate

Question 7

What are the two ways that a child gets affected by Achondroplasia

Answer 7

It can be inherited from an affected parent following autosomal dominant inheritance pattern or
It can occur as a spontaneous mutation in the fathers germ cells (majority)

Question 8

What rules apply to Autosomal recessive inheritance

Answer 8

1. Affects/ transmitted by both sex
2. Affected people usually born to unaffected parents
3. Increased incidence if parental consanguinity
4. After the birth of one affected child, each subsequent child has 25% chance of being affected

Question 9

What is the mechanism behind Hereditary haemochromatosis

Answer 9

It is a disorder of iron metabolism- increased iron absorption or excess iron accumulation which overtime causes multiorgan dysfunction due to iron deposition

Question 10

What are clinical features of Hereditary haemochromatosis

Answer 10

Common in caucasians. late onset of symptoms and equal incidence in both sexes.

• arthritis
• lethargy
• cardiomyopathy
• diabetes
• hypogonadism
• skin pigmentation
• hepatic cirrhosis

Question 11

Hereditary Haemochromatosis has locus heterogeneity. What locuses does this include

Answer 11

Mutations in

1. HFE gene (95%)
2. hemojuvelin and hepcidin - juvenile hemochromatosis
3. Transferrin Receptor protein 2

Question 12

How is haemochromatosis now diagnosed

Answer 12

Based on abnormal iron studies and HFE gene testing, with liver biopsy only done with negative test and concern about cirrhosis.

Question 13

What is the gene product of an autosomal recessive disorder

Answer 13

enzyme or diffusible protein