Figure 7. Genomic organization of imprinting clusters 11p15 (A) and 15q11–13 (B). Defects within imprinting cluster 11p15 are associated with Beckwith-Wiedemann-Syndrome (BWS). In BWS-1 patients, the maternal alleles acquire aberrant methylation within imprinting center (IC) 1, while IC2 remains normally methylated, resulting in silencing of H19 and biallelic expression of insulin-like growth factor 2. BWS-2 patients show loss of methylation within IC2, while IC1 remains unmethylated as normal, resulting in silencing of CDKN1C and biallelic expression of KCNQ1OT1. Defects within imprinting cluster 15q11–13 are associated with Prader-Willi syndrome if the deletion concerns the paternal chromosome—the candidate gene is the maternally imprinted SNRPN (not shown)—or Angelman syndrome if the deletion concerns the maternal chromosome—the candidate gene is the paternally imprinted UBE3A. While the majority of patients show a de novo deletion of the 15q11–13 region or a uniparental disomy, a few patients reveal aberrant imprinting and gene silencing. For further information, see Nicholls and Knepper (2001), Buiting et al (2003), Lucifero et al (2004a), Horsthemke and Ludwig (2005), and Kantor et al (2006). DMD indicates differentially methylated domain. Arrows indicate transcription.