Data from: Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal

Single-gene mutations account for more than 6000 diseases, 10% of all pediatric hospital admissions, and 20% of infant deaths. Down syndrome and other aneuploidies occur in more than 0.2% of births worldwide and are on the rise because of advanced reproductive age. Birth defects of genetic origin can be diagnosed in utero after invasive extraction of fetal tissues. Noninvasive testing with circulating cell-free fetal DNA is limited by a low fetal DNA fraction. Both modalities are unavailable until the end of the first trimester. We have isolated intact trophoblast cells from Papanicolaou smears collected noninvasively at 5 to 19 weeks of gestation for next-generation sequencing of fetal DNA. Consecutive matched maternal, placental, and fetal samples (n = 20) were profiled by multiplex targeted DNA sequencing of 59 short tandem repeat and 94 single-nucleotide variant sites across all 24 chromosomes. The data revealed fetal DNA fractions of 85 to 99.9%, with 100% correct fetal haplotyping. This noninvasive platform has the potential to provide comprehensive fetal genomic profiling as early as 5 weeks of gestation.

单基因突变可诱发超过6000种疾病，占儿科住院总病例数的10%，并导致20%的婴儿死亡。唐氏综合征（Down syndrome）及其他非整倍体疾病在全球活产儿中的发生率超过0.2%，且受高龄生育因素影响，其发病率呈上升趋势。遗传源性出生缺陷可通过侵入性获取胎儿组织的方式，在子宫内完成诊断。基于循环游离胎儿DNA（circulating cell-free fetal DNA）的无创检测技术，则因胎儿DNA占比偏低而存在局限性。上述两种检测方式均需等到妊娠第一孕期结束后方可开展。本研究从妊娠5至19周时无创采集的巴氏涂片（Papanicolaou smear）样本中分离得到完整的滋养层细胞，用于胎儿DNA的下一代测序（next-generation sequencing）。研究团队对20例匹配的连续母体、胎盘及胎儿样本，采用多重靶向DNA测序技术，对24条染色体上的59个短串联重复序列（short tandem repeat）位点与94个单核苷酸变异（single-nucleotide variant）位点进行了测序分析。结果显示，样本中胎儿DNA占比介于85%至99.9%之间，胎儿单倍型分型准确率达到100%。该无创检测平台有望在妊娠最早5周时，即可提供全面的胎儿基因组分型检测服务。