Genome-wide single nucleotide polymorphism array analysis unveils the origin of heterozygous androgenetic complete moles. Genome-wide single nucleotide polymorphism array analysis unveils the origin of heterozygous androgenetic complete moles

Heterozygous CHMs have been believed as synonymous with dispermic moles (two sperm origin). The possibility of diploid sperm origin has not been considered. We assessed whether heterozygous CHMs would be of dispermic or diploid sperm origin. In all the cases, centromeric zygosity was random, i.e., mixed status. Theoretically, if the heterozygous CHMs were of diploid sperm origin, the centromeric status will be all homozygous or all heterozygous. Thus, all the analyzed heterozygous CHMs were considered to be of dispermic origin. Three cases showed the trisomy while we did not notice them with STR analysis. Diploid sperm fertilization can be rare during the development of heterozygous androgenetic CHM. Overall design: The villous genomic DNA of the thirteen heterozygous CHMs was further analyzed using the single nucleotide polymorphism array. B allele frequency (BAF) plotting was used to determine the centromeric zygosity status of all chromosomes to discriminate dispermic origin from diploid sperm origin.

杂合性葡萄胎（CHM）既往被认为与双精子起源葡萄胎（即双精子来源）为同一概念，尚未考虑二倍体精子起源的可能性。本研究旨在评估杂合性CHM究竟为双精子起源还是二倍体精子起源。所有纳入病例的着丝粒合子型均呈随机分布状态，即呈现混合基因型。理论上，若杂合性CHM为二倍体精子起源，则所有染色体的着丝粒合子型应均为纯合型或杂合型。据此，本研究中所有被分析的杂合性CHM均被判定为双精子起源。本研究中有3例病例存在三体性，但通过短串联重复序列（STR, Short Tandem Repeat）分析未能检出该异常。在杂合性孤雄葡萄胎（androgenetic CHM）的发生发展过程中，二倍体精子受精事件较为罕见。实验整体设计：对13例杂合性CHM的绒毛基因组DNA开展进一步分析，采用单核苷酸多态性（SNP, Single Nucleotide Polymorphism）阵列技术，通过绘制B等位基因频率（BAF）图谱确定所有染色体的着丝粒合子型状态，以此区分双精子起源与二倍体精子起源。