The human homolog of a mouse-imprinted gene, Peg3, maps to a zinc finger gene-rich region of human chromosome 19q13.4.

Peg3 (paternally expressed gene 3) is the first imprinted gene detected in the proximal region of mouse chromosome 7 (Kuroiwa et al. 1996). The Peg3 transcription unit encodes a Kruppel-type (C2H2) zinc finger-containing (ZNF) protein, most of which are thought to function as transcription factors (El-Baradi and Pieler 1991; Pieler and Bellefroid 1994). Genetic studies have indicated that there are three different imprinted regions along the length of mouse chromosome 7 (Mmu7), located in proximal, central, and distal regions of the chromosome, respectively (Searle and Beechey 1990; Cattanach et al. 1992). Studies of several imprinted domains, including those located in central and distal Mmu7, the t-maternal effect (tme) region of Mmu17, and related regions of the human genome, have indicated that imprinted domains are generally large enough to encompass several genes (Efstratiadis 1994; Nicholls 1994; Barlow 1995). Although exceptions have been noted (Kalscheuer et al. 1993; Riesewijk et al. 1996), these previous studies have also provided evidence that genomic imprinting is generally conserved between orthologous genes in mammalian species (Barlow 1995). Human regions that are syntenically homologous to two of the three Mmu7-imprinted domains are associated with imprinted genetic disorders. Human chromosome 15q11-q13, which contains genes associated with Prader–Willi and Angelman syndromes, represents the human counterpart of the central Mmu7-imprinted region (Nicholls 1993, 1994), whereas Beckwith–Wiedemann syndrome genes are located in a region of 11p15.5 that is closely related to the most distal Mmu7-imprinted domain (Reik 1989; Efstratiadis 1994). However, the human counterpart of Peg3 has not yet been characterized, and gene content and inheritance patterns of the region surrounding the human gene have not been explored. In addition, although the embryonic expression patterns of mouse Peg3 are well-documented, expression of the gene in adult mouse tissues has not been investigated and the transcription pattern of homologous human sequences is unknown. Investigation of these basic characteristics of the human PEG3 gene represent the essential first steps toward understanding the possible role of the gene in imprinted human traits or health-related disorders. The proximal third of Mmu7 is closely related in gene content, order, and spacing to the long arm of human chromosome 19 (Saunders and Seldin 1990; Stubbs et al. 1996), making it likely that the human counterpart of Peg3 would be found in that human region. To gain more information about the human PEG3 gene and to provide tools for the discovery of other potentially imprinted genes, we have mapped human sequences related to the mouse Peg3 gene within the established physical map of human chromosome 19 (Ashworth et al. 1995). We have also determined the sequence of a human genomic fragment containing Peg3-related sequences and compared it with mouse Peg3. Finally, we have determined the expression patterns of PEG3 in human tissues and have compared these data with transcription patterns of Peg3 in the adult mouse. These studies lay the basic groundwork for investigating whether PEG3 and other human 19q13.4/Mmu7 genes, perhaps including some of the numerous ZNF-containing genes located in both the human and mouse regions, may also be imprinted in one or both species.