Minimal definition of the imprinting center and fixation of chromosome 15q11-q13 epigenotype by imprinting mutations.

• DOI: 10.1073/pnas.93.15.7811
• Publication Date: 2002-07-26T14:31:39Z
• Authors: S Saitoh; K Buiting; P K Rogan; J L Buxton; D J Driscoll; J Arnemann; R König; S Malcolm; B Horsthemke; R D Nicholls
• Keywords: Imprinting (psychology); Genomic Imprinting; Angelman Syndrome

Patients with disorders involving imprinted genes such as Angelman syndrome (AS) and Prader-Willi (PWS) can have a mutation in the imprinting mechanism. Previously, we identified an center (IC) within chromosome 15q11-ql3 proposed that IC mutations block resetting of imprint, fixing on parental imprint (epigenotype) which arose. We now describe four new microdeletions IC, smallest (6 kb) currently defines minimal region sufficient to confer AS mutation. The deletions all overlap this region, centromeric PWS microdeletions, include first exon SNRPN gene. None five or transcripts 1.0 Mb vicinity (ZNF127, SNRPN, PAR-5, IPW, PAR-1), each normally expressed only from paternal allele, was cells patients. In contrast, patients show biparental expression IPW but must lack putative gene 250-1000 kb distal IC. These data strongly support model these carries ancestral maternal epigenotype, epigenotype. therefore functions reset imprints throughout 2-Mb domain human 15q11-q13 during gametogenesis.