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Tetraploid Partial Hydatidiform Moles Molecular Genotyping and Determination of Parental Contributions.

DNA genotyping studies have established that most partial hydatidiform moles (PHM) are diandric dispermic triploid conceptions. Rare triandric tetraploid PHMs have been described but genotyping cannot determine the manner in which three paternal chromosome complements are derived (one sperm with triplication, two sperm with one duplication, three different sperm, one diploid, and one haploid sperm). In a large prospective analysis of potentially molar products of conception, five tetraploid PHMs were encountered among 235 PHMs. Single nucleotide polymorphism (SNP) arrays were used to define different paternal chromosomal contributions. STR analysis of the five tetraploid PHMs established that these contained three paternal and one maternal chromosome complements. In each case, the corresponding SNP array showed five tracts with segmented absence of the central tract across approximately 25% of the genome. Meiotic crossovers could be observed directly in the chromosomes via the total number of "starts and stops" of regions of loss of heterozygosity. The findings are consistent with each conceptus having three different paternal contributions and one maternal contribution. These findings suggest that tetraploid PHMs arise when three different sperm fertilize a single, normal ovum. SNP array is useful to determine the parental contributions in triploid/tetraploid conceptuses. It also allows for direct visualization of meiotic crossover frequency and sites in these conceptions, providing insight into their biology.

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