Question

Genetics: Combined Factor V & VIII

Part 1: Describe what happens to the product of the gene that causes the double clotting factor disorder in the ER and the golgi apparatus.Describe what happens to the product of the gene that causes the double clotting factor disorder in the ER and the golgi apparatus.

Part 2: What is the evidence that a mutation in a single gene causes this double deficiency? That is, how does the inheritance pattern differ from what it would be if families inherited each condition independently?

Answer 1

The product of genes LMAN1(lectin, mannose-specific 1) and MCFD2 (multiple coagulation factor deficiency gene 2) attach to the coagulation factors FV and FVIII directly within the ER and act as signals for transportation. The two factors are sorted out in ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment) where both factors are separated and transported to the Golgi Apparatus for O- glycosylation and N-glycosylation. This leads to formation of secretory vesicles that ultimately lead to exocytosis of both coagulation factors.

Families suffering from double clotting factor disorder will have a genetic mutation in one of the two genes: LMAN1 and MCFD2. Both genes will be responsible for secreting FV and FVIII. As such, if a parent has this deficiency, which is autosomal recessive, and other parent is heterozygous for one of the coagulation factors, by Mendelian inheritance, the probability of occurrence of double clotting factor disorder in the progenies will be 1/4. If both parents are heterozygous for the same allele (either FV or FVIII), their progenies will not have this disorder. If one parent is homozygous recessive and other is homozygous dominant, their progenies will not suffer from this disorder.