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We describe a complex imprinted locus in chromosome 15q11–q13 that encodes two genes,  ZNF127  and  ZNF127AS . The  ZNF127  gene encodes a protein with a RING (C 3 HC 4 ) zinc-finger and multiple C 3 H zinc-finger motifs, the former being closely related to a protein from variola major virus, the smallpox etiological agent. These motifs allow prediction of ZNF127 function as a ribonucleoprotein. The intronless  ZNF127  gene is expressed ubiquitously, but the entire coding sequence and 5′ CpG island overlaps a second gene,  ZNF127AS , that is transcribed from the antisense strand with a different transcript size and pattern of expression. Allele-specific analysis shows that  ZNF127 is expressed only from the paternal allele. Consistent with this expression pattern, in the brain the  ZNF127  5′ CpG island is completely unmethylated on the paternal allele but methylated on the maternal allele. Analyses of adult testis, sperm and fetal oocytes demonstrates a gametic methylation imprint with unmethylated paternal germ cells. Recent findings indicate that  ZNF127  is part of the coordinately regulated imprinted domain affected in Prader-Willi syndrome patients with imprinting mutations. Therefore,  ZNF127  and  ZNF127AS  are novel imprinted genes that may be associated with some of the clinical features of the polygenic Prader-Willi syndrome.

A Novel Imprinted Gene, Encoding a RING Zinc-Finger Protein, and Overlapping Antisense Transcript in the Prader-Willi Syndrome Critical Region