Paternal origins of complete hydatidiform moles proven by whole genome single-nucleotide polymorphism haplotyping.
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.
Fan
Jian-Bing
JB
Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA.
Surti
Urvashi
U
Taillon-Miller
Patricia
P
Hsie
Linda
L
Kennedy
Giulia C
GC
Hoffner
Lori
L
Ryder
Thomas
T
Mutch
David G
DG
Kwok
Pui-Yan
PY
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