Whole-genome sequencing (WGS) of maternal plasma cell-free DNA (cfDNA) can potentially evaluate all 24 chromosomes to identify abnormalities of the placenta, fetus, or pregnant woman. Current bioinformatics algorithms typically only report on chromosomes 21, 18, 13, X, and Y; sequencing results from other chromosomes may be masked. We hypothesized that by systematically analyzing WGS data from all chromosomes, we could identify rare autosomal trisomies (RATs) to improve understanding of feto-placental biology. We analyzed two independent cohorts from clinical laboratories, both of which used a similar quality control parameter, normalized chromosome denominator quality. The entire data set included 89,817 samples. Samples flagged for analysis and classified as abnormal were 328 of 72,932 (0.45%) and 71 of 16,885 (0.42%) in cohorts 1 and 2, respectively. Clinical outcome data were available for 57 of 71 (80%) of abnormal cases in cohort 2. Visual analysis of WGS data demonstrated RATs, copy number variants, and extensive genome-wide imbalances. Trisomies 7, 15, 16, and 22 were the most frequently observed RATs in both cohorts. Cytogenetic or pregnancy outcome data were available in 52 of 60 (87%) of cases with RATs in cohort 2. Cases with RATs detected were associated with miscarriage, true fetal mosaicism, and confirmed or suspected uniparental disomy. Comparing the trisomic fraction with the fetal fraction allowed estimation of possible mosaicism. Analysis and reporting of aneuploidies in all chromosomes can clarify cases in which cfDNA findings on selected “target” chromosomes (21, 18, and 13) are discordant with the fetal karyotype and may identify pregnancies at risk of miscarriage and other complications.

母体无浆细胞 DNA (cfDNA) 的全基因组测序 (WGS) 可以评估所有 24 条染色体，以确定胎盘、胎儿或孕妇的异常情况。当前的生物信息学算法通常只报告 21、18、13、X 和 Y 染色体；来自其他染色体的测序结果可能被掩盖。我们假设，通过系统地分析来自所有染色体的 WGS 数据，我们可以识别罕见的常染色体三体 (RAT)，以提高对胎儿胎盘生物学的理解。我们分析了来自临床实验室的两个独立队列，这两个队列都使用了相似的质量控制参数，标准化的染色体分母质量。整个数据集包括 89,817 个样本。在第 1 组和第 2 组中，标记为分析并归类为异常的样本为 72,932 例中的 328 例 (0.45%) 和 16,885 例中的 71 例 (0.42%)，分别。队列 2 中 71 例异常病例中有 57 例 (80%) 的临床结果数据可用。WGS 数据的视觉分析显示 RAT、拷贝数变异和广泛的全基因组失衡。7、15、16 和 22 三体是两个队列中最常观察到的 RAT。队列 2 中 60 例 RAT 病例中有 52 例 (87%) 有细胞遗传学或妊娠结局数据。检测到 RAT 的病例与流产、真正的胎儿嵌合体以及确诊或疑似单亲二体性有关。将三体分数与胎儿分数进行比较可以估计可能的镶嵌现象。分析和报告所有染色体中的非整倍体可以澄清 cfDNA 在选定“目标”染色体上发现的案例 (21, 18,