致病性变体的透率很低,并由共同的遗传背景形成
Remi Stevelink1,2, M Martijn Piet1,2, Yorgos Bos2
1Department of Child Neurology, University Medical Center Utrecht, member of European Reference Network EpiCARE, Utrecht, the Netherlands.
发育性脑病变 (DEE) 的变异透率低于之前的假设. 多原风险得分 (PRS) 改变风险,高PRS增加了致病变体携带者的严重风险.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 的研究研究.
- 临床基因组学 临床基因组学
背景情况:
- 发育性脑病变 (DEE) 基因的致病变体对于遗传咨询和治疗至关重要.
- 以前,变种透率被认为是高或完全的,缺乏基于人口的验证.
- 新出现的证据表明,多基因风险评分 (PRS) 可能会影响DEE风险.
研究的目的:
- 在大型队列中确定自体主导变异的透率.
- 调查PRS评估的常见变异是否会在致病变异携带者中改变风险.
主要方法:
- 通过使用全基因组测序,计算了来自ClinVar的 (可能) 致病变体在两个大队列 (n=42,863和n=386,306) 的透率.
- 评估了PRS对携带致病变体的个体风险的影响.
主要成果:
- 大多数致病性DEE变异携带者没有表现出.
- 据估计,携带者的透率在4.1%至9.8%之间.
- 较高的PRS与严重的风险增加相关,而较低的PRS在携带者中似乎具有保护性.
结论:
- 对DEE的变异透率低于预期,并受到PRS的影响.
- 一种致病变体和高PRS的组合可能需要用于严重现型,如DEE.
- 修订的透率估计可以改善变体分类,诊断产量和遗传咨询准确性.
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