A model system to study genomic imprinting of human genes

Somatic-cell hybrids have been shown to maintain the correct epigenetic chr omatin states to study developmental globin gene expression as well as gene expression on the active and inactive X chromosomes. This suggests the pot ential use of somatic-cell hybrids containing either a maternal or a patern al human chromosome as a model system to study known imprinted genes and to identify as-yet-unknown imprinted genes. Testing gene expression by using reverse transcription followed by PCR, we show that functional imprints are maintained at four previously characterized 15q11-q13 loci in hybrids cont aining a single human chromosome 15 and at two chromosome 11p15 loci in hyb rids containing a single chromosome II. In contrast, three gamma-aminobutyr ic acid type A receptor subunit genes in 15q12-q13 are nonimprinted. Furthe rmore, we have found that differential DNA methylation imprints at the SNRP N promoter and at a CpG island in 11p15 are also maintained in somatic-cell hybrids. Somatic-cell hybrids therefore are a valid and powerful system fo r studying known imprinted genes as well as for rapidly identifying new imp rinted genes.