title: Paternal origins of complete hydatidiform moles proven by whole genome single-nucleotide polymorphism haplotyping.
abstract: Complete hydatidiform moles (CHMs) are diploid tumors that result from fertilization of an empty ovum by a haploid 23,X sperm. In most cases, the resulting duplication of the genome gives rise to a 46,XX genotype and is thought to be androgenetic in origin. If this hypothesis is correct, then the genotypes of all polymorphic markers in CHMs should be homozygous. We used a dense set of single-nucleotide polymorphism (SNP) markers, evenly spaced throughout the genome, to definitively test this hypothesis. We genotyped genomic DNA samples from five CHMs and their corresponding maternal samples with 1494 SNP markers using high-density microarrays (HuSNP). As predicted, the maternal samples were heterozygous at >25% of the markers, which is consistent with the expected average heterozygosity of this panel of SNPs. In contrast, the five CHM samples were heterozygous at <0.75% of the SNP markers, which shows that these diploid tumors consist of a duplicated set of chromosomes. Because the CHM genotypes represent the haplotypes of their genomes, our results show that long-range haplotypes can be obtained easily with this resource and that a collection of such samples is a simple way to obtain reference haplotypes for association studies in various populations.
authors.affiliation: Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Urvashi
authors.initials: U
authors.lastname: Surti
authors.forename: Patricia
authors.initials: P
authors.lastname: Taillon-Miller
authors.forename: Linda
authors.initials: L
authors.lastname: Hsie
authors.forename: Giulia C
authors.initials: GC
authors.lastname: Kennedy
authors.forename: Lori
authors.initials: L
authors.lastname: Hoffner
authors.forename: Thomas
authors.initials: T
authors.lastname: Ryder
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
mesh_terms: D005260:Female; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D006828:Hydatidiform Mole / Q000209:etiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy