**2.2.2 Assembly of the Prader-Willi/Angelman's syndrome locus**

Mutations in imprinted genes on human chromosome 15q11-q13 are responsible for the neurological disorders Prader-Willi and Angelman's syndrome. Imprinting of genes in this region is controlled by an imprinting control region (ICR) located within the Prader-Willi/Angelman's syndrome domain (Kantor et al., 2004). The ICR is flanked by the paternally expressed *SNRPN* gene and maternally expressed *UBE3A.* A cross-species comparison of the arrangement of these two genes across vertebrates uncovered an unexpected finding. A wallaby BAC clone containing the *SNRPN* gene mapped to wallaby chromosome 1, whereas the BAC containing the *UBE3A* localized to the short arm of chromosome 5. Furthermore, a fully sequenced platypus BAC clone containing *UBE3A* identified the gene adjacent to be *CNGA3*, a human chromosome 2 gene (Rapkins et al., 2006). Subsequent analysis of the chicken, zebrafish and opossum genome sequence assemblies unequivocally showed this to be the ancestral arrangement, with *UBE3A* adjacent to *CNG3A* while *SRNPN* is located elsewhere in the genome. Both *UBE3A* and *SRNPN* were found to be biallelic expressed in marsupials and monotremes. It appears that the other imprinted genes found in this region in eutherians do not exist in marsupials and originated from RNA copies of genes located in other parts of the genome. Rapkins et al (2006) concluded that these genes only became subject to genomic imprinting when the region was assembled in the eutherian lineage. This study also provided the first evidence that genomic imprinting was acquired by different loci at different times during mammalian evolution.
