McCarty Keelee J, Haywood Mary E, Lee Rachel, Henry Lauren, Arnold Alison, McReynolds Susanna, McCallie Blair, Schoolcraft Bill, Katz-Jaffe Mandy
Colorado Center of Reproductive Medicine, Lone Tree, CO, USA.
Mol Hum Reprod. 2022 Dec 28;29(1). doi: 10.1093/molehr/gaac040.
The aim of this study was to characterize a large set of full segmental aneuploidies identified in trophectoderm (TE) biopsies and evaluate concordance in human blastocysts. Full segmental aneuploid errors were identified in TE biopsies (n = 2766) from preimplantation genetic testing for aneuploid (PGT-A) cycles. Full segmental deletions (n = 1872; 66.1%) presented twice as many times as duplications (n = 939; 33.9%), mapped more often to the q-arm (n = 1696; 61.3%) than the p-arm (n = 847; 31.0%) or both arms (n = 223; 8.1%; P < 0.05), and were eight times more likely to include the distal end of a chromosome than not (P < 0.05). Additionally, 37 recurring coordinates (each ≥ 10 events) were discovered across 17 different chromosomes, which were also significantly enriched for distal regions (P = 4.1 × 10-56). Blinded concordance analysis of 162 dissected blastocysts validated the original TE PGT-A full segmental result for a concordance of 96.3% (n = 156); remaining dissected blastocysts were identified as mosaic (n = 6; 3.7%). Origin of aneuploid analysis revealed full segmental aneuploid errors were mostly paternally derived (67%) in contrast to whole chromosome aneuploid errors (5.8% paternally derived). Errors from both parental gametes were observed in 6.5% of aneuploid embryos when multiple whole chromosomes were affected. The average number of recombination events was significantly less in paternally derived (1.81) compared to maternally derived (3.81) segmental aneuploidies (P < 0.0001). In summary, full segmental aneuploidies were identified at hotspots across the genome and were highly concordant upon blinded analysis. Nevertheless, future studies assessing the reproductive potential of full (non-mosaic) segmental aneuploid embryos are critical to rule out potential harmful reproductive risks.
本研究的目的是对在滋养外胚层（TE）活检中鉴定出的大量全片段非整倍体进行特征描述，并评估人类囊胚中的一致性。在用于非整倍体植入前基因检测（PGT-A）周期的TE活检（n = 2766）中鉴定出全片段非整倍体错误。全片段缺失（n = 1872；66.1%）出现的次数是重复（n = 939；33.9%）的两倍，更多地定位于q臂（n = 1696；61.3%）而非p臂（n = 847；31.0%）或双臂（n = 223；8.1%；P < 0.05），并且包含染色体远端的可能性是不包含的八倍（P < 0.05）。此外，在17条不同染色体上发现了37个重复坐标（每个≥10次事件），这些坐标在远端区域也显著富集（P = 4.1×10-56）。对162个解剖后的囊胚进行的盲法一致性分析验证了原始TE PGT-A全片段结果的一致性为96.3%（n = 156）；其余解剖后的囊胚被鉴定为嵌合体（n = 6；3.7%）。非整倍体起源分析显示，与全染色体非整倍体错误（父源占5.8%）相比，全片段非整倍体错误大多源自父方（67%）。当多个全染色体受到影响时，在6.5%的非整倍体胚胎中观察到来自双亲配子的错误。与母源（3.81）全片段非整倍体相比，父源全片段非整倍体的平均重组事件数显著更少（1.81）（P < 0.0001）。总之，全片段非整倍体在全基因组的热点区域被鉴定出来，并且在盲法分析中具有高度一致性。然而，未来评估全（非嵌合）片段非整倍体胚胎生殖潜力的研究对于排除潜在的有害生殖风险至关重要。
