Chapter 13, Problem 25P

Duchenne muscular dystrophy (DMD) is caused by a recessive mutant allele of an X-linked gene called dystrophin. Rarely, females have disease symptoms as severe as those in males hemizygous for the recessive allele. These females are heterozygous for X-autosome reciprocal translocations where the X chromosome breakage occurred in the middle of the dystrophin gene, breaking it into two pieces.

a.	If it is equally likely for X chromosome inactivation to spread from either of the X chromosome inactivation centers (XICs; see Fig. 12.15) in the cells of this patient, what proportion of her cells would you expect to have normal function of the dystrophin gene?
b.	Is it possible that some autosomal genes might be inactivated in some cells of this woman? Is it possible that some X-linked genes that are normally subject to X inactivation might be expressed from both X chromosomes in this woman? To answer these questions, draw a figure showing the normal and translocated chromosomes involved, and the locations of: centromeres, potentially inactivated autosomal genes, X chromosome genes potentially no longer subject to X inactivation, the dystrophin gene, and the XICs. Assume for simplicity that dystrophin and the XIC are located in the middle of the short and long arms of the X chromosome, respectively.
c.	It is found that virtually none of the cells in this woman expresses any of the dystrophin gene product. Use your answers to parts (a) and (b) to explain this interesting observation. Consider what changes in gene expression might do to the survival and proliferation of cells.
d.	Discuss how scientists might have used X:autosome reciprocal translocations to help map the XIC on the human X chromosome. Why does your answer to part (c) illustrate a potential pitfall of this approach?