Early embryonic failure associated with uniparental disomy for human chromosome 21

As many as 16% of all recognized pregnancies may be anembryonic, with failure of the embryo at a very early stage of development leaving only the extraembryonic components of the conceptus to proliferate. Studies in the mouse have shown that the maternal and paternal contributions to the genome of the zygote are not functionally equivalent, due to parental genomic imprinting. Uniparental disomy can reveal imprinting effects, as in this phenomenon both members of a chromosome pair are inherited from the same parent. We have carried out a systematic search for uniparental disomy in tissues from 23 cases of early embryonic failure, using variable number tandem repeat (VNTR) analysis and PCR amplification of polymorphic short sequence repeats. Two cases of maternal uniparental heterodisomy for chromosome 21 were identified. One case occurred in conjunction with trisomy for chromosomes 7 and 9, but in the other case maternal uniparental heterodisomy for chromosome 21 was the only chromosomal abnormality found. We therefore postulate that there may be developmentally important genes on human chromosome 21 which are imprinted such that both parental copies are essential for normal embryogenesis.