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新方法助力人胚胎着床前常见疾病的风险预测
作者:小柯机器人 发布时间:2022/3/27 14:19:09

美国MyOme公司Akash Kumar课题组取得一项新突破。他们研究出人胚胎着床前常见病全基因组风险预测方法。2022年3月21日,国际学术期刊《自然-医学》发表了这一成果。

研究人员使用分子和统计技术相结合的方法推测了110个胚胎中的遗传基因组序列,并模拟12种常见疾病的发生概率。研究人员在第5天胚胎活检病例中观察到与多基因风险评分相关位点的基因型准确度为99.0-99.4%,在第3天胚胎活检病例中的准确率为97.2-99.1%。将罕见变异与多基因风险评分(PRS)相结合,可以放大相关胚胎之间的预测差异。例如,在具有致病性BRCA1变异的一对夫妇中,研究人员预测,使用BRCA1或PRS相结合方法预测相邻胚胎间的优势比(OR)差异为与单独使用BRCA1或PRS的15倍或3倍。该研究结果有利于着床前基因检测(PGT)在临床实践中的效用和实施。

据了解,对体外受精胚胎进行PGT是一种减少常见疾病传播的方法;然而,仍然无法进行对包含常见变异和罕见变异进行更全面的胚胎遗传评估。

附:英文原文

Title: Whole-genome risk prediction of common diseases in human preimplantation embryos

Author: Kumar, Akash, Im, Kate, Banjevic, Milena, Ng, Pauline C., Tunstall, Tate, Garcia, Geronimo, Galhardo, Luisa, Sun, Jiayi, Schaedel, Oren N., Levy, Brynn, Hongo, Donna, Kijacic, Dusan, Kiehl, Michelle, Tran, Nam D., Klatsky, Peter C., Rabinowitz, Matthew

Issue&Volume: 2022-03-21

Abstract: Preimplantation genetic testing (PGT) of in-vitro-fertilized embryos has been proposed as a method to reduce transmission of common disease; however, more comprehensive embryo genetic assessment, combining the effects of common variants and rare variants, remains unavailable. Here, we used a combination of molecular and statistical techniques to reliably infer inherited genome sequence in 110 embryos and model susceptibility across 12 common conditions. We observed a genotype accuracy of 99.0–99.4% at sites relevant to polygenic risk scoring in cases from day-5 embryo biopsies and 97.2–99.1% in cases from day-3 embryo biopsies. Combining rare variants with polygenic risk score (PRS) magnifies predicted differences across sibling embryos. For example, in a couple with a pathogenic BRCA1 variant, we predicted a 15-fold difference in odds ratio (OR) across siblings when combining versus a 4.5-fold or 3-fold difference with BRCA1 or PRS alone. Our findings may inform the discussion of utility and implementation of genome-based PGT in clinical practice.

DOI: 10.1038/s41591-022-01735-0

Source: https://www.nature.com/articles/s41591-022-01735-0

 

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex