The evolution of genomic imprinting in mammals occurred more than 100 million 
years ago, and resulted in the formation of genes that are functionally haploid 
because of parent-of-origin-dependent expression. Despite ample evidence from 
studies in a number of species suggesting the presence of imprinted genes on 
human chromosome 14, their identity has remained elusive. Here we report the 
identification of two reciprocally imprinted genes, GTL2 and DLK1, which 
together define a novel imprinting cluster on human chromosome 14q32. The 
maternally expressed GTL2 (gene trap locus 2) gene encodes for a nontranslated 
RNA. DLK1 (delta, Drosophila, homolog-like 1) is a paternally expressed gene 
that encodes for a transmembrane protein containing six epidermal growth factor 
(EGF) repeat motifs closely related to those present in the delta/notch/serrate 
family of signaling molecules. The paternal expression, chromosomal 
localization, and biological function of DLK1 also make it a likely candidate 
gene for the callipyge phenotype in sheep. Many of the predicted structural and 
regulatory features of the DLK1/GTL2 domain are highly analogous to those 
implicated in IGF2/H19 imprint regulation, including two hemimethylated 
consensus binding sites for the vertebrate enhancer blocking protein, CTCF. 
These results provide evidence that a common mechanism and domain organization 
may be used for juxtapositioned, reciprocally imprinted genes.