Variant Effects and Linkage

Question 1

What percentage of people of northern european decent are carriers of Cystic Fibrosis?

Answer 1

1/ 25%

Question 2

Define Dominant Negative variants and give an example.

Answer 2

A variant that results in a protein that adversely affects the normal product within the same cell.

Osteogenesis imperfecta is an example because the collagen fibres produced by the disease allele will affect all three-stranded collagen fibres making all of them suck rather than just half.

Question 3

Do SHH variants tend to be haplosufficient?

Answer 3

No, a single mutated copy of the SHH gene will be haploinsufficient and result in holoprosencephaly.

Question 4

Give an example of a LoF and a GoF for the Pax3 gene.

Answer 4

LoF: Waardenburg syndrome

GoF: Alveolar rhabdomyosarcoma