IMPRINTED EXPRESSION OF SNRPN IN HUMAN PREIMPLANTATION EMBRYOS

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinica lly distinct neurogenetic disorders arising from a loss of expression of imprinted genes within the human chromosome region 15q11-q13. Recen t evidence suggests that the SNRPN gene, which is defective in PWS, pl ays a central role in the imprinting-center regulation of the PWS/AS r egion. To increase our understanding of the regulation of expression o f this imprinted gene, we have develop ed single-cell-sensitive proced ures for the analysis of expression of the SNRPN gene during early hum an development. Transcripts of SNRPN were detected in human oocytes an d at all stages of preimplantation development analyzed. Using embryos heterozygous for a polymorphism within the SNRPN gene, we showed that monoallelic expression from the paternal allele occurs by the 4-cell stage. Thus, the imprinting epigenetic information inherited in the ga metes is recognized already in the preimplantation embryo. The demonst ration of monoallelic expression in embryos means that efficient preim plantation diagnosis of PWS may be made by analysis for the presence o r absence of SNRPN mRNA.