Loss of 15q 12, the PWS/AS region produces different symptoms depending on the parent of origin. PWS results from the loss of paternal copies of this region. Deletion of the same region on the maternal chromosome causes AS.

Human SNRPN, a gene in the deleted region is monoallelically expressed in normal fetal brain and heart and in adult brain. Analysis of maternal DNA and SNRPN cDNA confirmed that the maternal allele of SNRPN is not expressed in fetal brain and heart. Maternal imprinting of SNRPN supports the hypothesis that paternal absence of SNRPN is responsible for the PWS phenotype. Thus it is reasonable to assume that PWS symptoms result at least in part from the absence of SNRPN. Of course the assumption is a hypothesis and testing is always a good idea in science. Which of the following experimental suggestions might provide evidence to support or refute the hypothesis that SNRPN absence leads to PWS?

a. use a b-galactosidase reporter to show that SNRPN is maternally imprinted

b. use a constitutive promoter construct to turn SNRPN on in the male parent’s deletion

c. use siRNA to silence SNRPN in normal male parents

d. use a CCKa deleted maternal SNRPN to facilitate imprinting

e. use PstI to digest the male, deletion parents DNA and probe for SNRPN