Determining the genetic cause of the X-chromosome inactivation skewing observed in an atlantic Canadian family with hemophilia A

I am studying a family with hemophilia A in women. This is unusual because the hemophilia A gene is located on the X-chromosome, so males, who only have one X-chromosome, are usually the only ones affected. Females with hemophilia A on one side of their family are not usually affected. I have found that the affected females in this family have the disease because of unusual X-chromosome inactivation (XCI). This is a process occurring in women where one X-chromosome in each cells is shut off. This has to happen because females have twice the X-linked genes of males. Whether the mother¿s X or the father¿s X is shut off in any given cell is thought to be randomly determined. I have shown that the affected women in this family do not have random XCI. They have shut off most of their X¿s with the normal hemophilia A gene. This suggests that XCI is genetically influenced in this family. I am trying to find the gene that is involved. Identifying this gene will help us predict whether other females will be affected by hemophilia A or other X-linked diseases. Thus, this work is of particular importance to women¿s and children¿s health. Understanding the basic biology of XCI is also relevant to other biological process involving gene silencing including cancer and ageing.