Screening embryos for polygenic conditions and traits: ethical considerations for an emerging technology.
Screening embryos for polygenic conditions and traits: ethical considerations for an emerging technology.
复制标题
筛查胚胎的多基因条件和特征：一项新兴技术的伦理考量。
DOI：
10.1038/s41436-020-01019-3
复制
发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Lencz T
中科院分区：
文献类型：
--
作者：
Lázaro-Muñoz G;Pereira S;Carmi S;Lencz T
多基因胚胎筛查(PES)-使用复杂表型的多基因风险评分作为植入前基因测试(PGT)的一个组成部分-已经成为一项商业可用的服务，尽管公众几乎没有考虑过它的伦理、临床和社会影响。1、2相比之下，PGT多年来一直被用来避免植入含有非整倍体(如PGTA)或预先指定的单基因致病等位基因(PGTM)的胚胎，大量文献探讨了有意义的知情同意、生殖自主和公平等问题。3-5在某些方面，PES加剧了先前阐明的PGT的困境，特别是现在PGT-M的覆盖范围已经扩大到成人发病疾病的可变渗透性致病变种(例如BRCA1)。然而，PES也提出了在植入前遗传学背景下在许多方面都是新的伦理关切。在PES中，使用全基因组技术，如单核苷酸多态(SNP)微阵列或测序，对来自体外受精(IVF)的一批胚胎进行基因分型。然后，为每个胚胎生成多基因风险评分(PRS)，以估计常见疾病(如糖尿病、抑郁症、各种癌症)或数量性状(如身高)的可能性。然后根据这些多基因评分选择胚胎进行植入。最近的两项技术发展使PES成为可能：首先，复杂性状遗传学的进步导致了来自大规模全基因组关联研究(Gwas)的PRSS的发展，7捕捉到了数千个微小等位基因对复杂性状的影响。其次，从囊胚或卵裂期胚胎中获得有限的输入材料，现在就可以产生准确的全基因组基因型别。8
Polygenic embryo screening (PES)—the use of polygenic risk scores for complex phenotypes as a component of preimplantation genetic testing (PGT)—has emerged as a commercially available service, despite almost no public deliberation about its ethical, clinical, and societal implications. 1, 2 By contrast, PGT has been used for many years to avoid implantation of embryos harboring aneuploidies (eg, PGTA) or prespecified, monogenic disease-causing alleles (PGTM), and a large literature has explored questions about meaningful informed consent, procreative autonomy, and equity issues, among many others. 3–5 In some ways, PES exacerbates previously articulated dilemmas in PGT, especially now that the reach of PGT-M has expanded to variably penetrant pathogenic variants for adult-onset diseases (eg, BRCA1). 6 However, PES also raises ethical concerns that are in many ways novel in the preimplantation genetics context. In PES, a batch of embryos derived from in vitro fertilization (IVF) is genotyped using a genome-wide technology such as single-nucleotide polymorphism (SNP) microarrays or sequencing. Then, polygenic risk scores (PRSs) are generated for each embryo to estimate the likelihood of common diseases (eg, diabetes, depression, various cancers) or quantitative traits (eg, height). An embryo is then selected for implantation on the basis of these polygenic scores. PES was made possible by two recent technical developments: first, progress in complex traits genetics has led to the development of PRSs derived from large-scale genome-wide association studies (GWAS), 7 capturing the contributions of thousands of tiny allelic effects on complex traits. Second, it is now feasible to generate accurate genome-wide genotypes from limited input material available from blastocysts or cleavage stage embryos. 8
登录
查看更多内容
影响因子：
7.7
作者：
Mostafavi, Hakhamanesh;Harpak, Arbel;Przeworski, Molly
通讯作者：
Przeworski, Molly
影响因子：
16.6
作者：
Duncan, L.;Shen, H.;Domingue, B.
通讯作者：
Domingue, B.
影响因子：
3.4
作者：
Sueoka, Kou
通讯作者：
Sueoka, Kou
影响因子：
8.2
作者：
Hadar, Liat;Sood, Sanjay
通讯作者：
Sood, Sanjay
影响因子：
6.7
作者：
Daar, Judith;Benward, Jean;Zweifel, Julianne
通讯作者：
Zweifel, Julianne