TY - JOUR
T1 - Paternal origins of complete hydatidiform moles proven by whole genome single-nucleotide polymorphism haplotyping
AU - Fan, Jian Bing
AU - Surti, Urvashi
AU - Taillon-Miller, Patricia
AU - Hsie, Linda
AU - Kennedy, Giulia C.
AU - Hoffner, Lori
AU - Ryder, Thomas
AU - Mutch, David G.
AU - Kwok, Pui Yan
N1 - Funding Information:
We thank Lixin Zhou and Semyon Kruglyak at Illumina for help in preparing the tables and figures, and data analysis, and Weiwei Liu and Joyce Chen at Affymetrix for technical assistance. This work is supported in part by grants from the National Human Genome Research Institute (HG1439 to P.-Y.K. and HG1720 to P.-Y.K. and U.S.).
PY - 2002/1
Y1 - 2002/1
N2 - 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.
AB - 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.
KW - Complete hydatidiform mole
KW - DNA chip
KW - DNA microarray
KW - Genotype
KW - Genotyping
KW - Haplotype
KW - Microarray
KW - SNP
KW - Single-nucleotide polymorphism
KW - Whole genome haplotyping
UR - http://www.scopus.com/inward/record.url?scp=0035701287&partnerID=8YFLogxK
U2 - 10.1006/geno.2001.6676
DO - 10.1006/geno.2001.6676
M3 - Article
C2 - 11827458
AN - SCOPUS:0035701287
SN - 0888-7543
VL - 79
SP - 58
EP - 62
JO - Genomics
JF - Genomics
IS - 1
ER -