在不同的人群中,遗传疾病负担对疾病的倾向
Barış Kayaalp1, Meltem Ece Kars2, Yuval Itan2,3,4
1Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara, Türkiye.
NPJ genomic medicine
|February 18, 2026
概括
个体平均携带4.70种致病或可能致病的遗传变异,其中11种中有1种具有可操作的基因型. 这些遗传数据有助于个性化医疗和预防性健康策略.
科学领域:
- 遗传学 遗传学 是一个
- 基因组医学是基因组医学.
- 计算生物学 计算生物学
背景情况:
- 遗传变异在孟德尔条件中起着至关重要的作用.
- 大规模的基因组数据库对于变体解释至关重要.
- 了解致病变体的负担是公共卫生的关键.
研究的目的:
- 在广泛的疾病基因谱中识别和量化致病和可能致病的变体.
- 估计人口中可操作的基因型和载体查候选人的流行率.
- 通过基因组第一方法探索对各种疾病群体的遗传倾向.
主要方法:
- 从gnomAD,Regeneron遗传中心的百万个exome和土耳其的variome中提升了等位基因频率.
- 利用了由PanelApp和OMIM策划的4591个疾病基因的数据.
- 采用美国医学遗传学与基因组学学院 (ACMG) 基于分类器来识别致病性和可能致病性变体.
主要成果:
- 确定了97,135种致病性和478,263种可能致病性变体,扩大了已知的目录近六倍.
- 确定个体平均携带4.70种致病或可能致病的变体,其中1.66种与孟德尔条件相容.
- 发现11个个体中有1个具有可操作的基因型,并确定了382个用于载体查的候选基因.
- 在13个ICD-10疾病组中发现了显著的遗传倾向,包括先天性,肌肉骨/连接器和血液/免疫疾病.
结论:
- 这项研究提供了致病性和可能致病性变体的全面目录,显著增强了遗传变体的解释.
- 这些发现突出了基因变异和可操作的基因型在一般人群中的重大负担.
- 基于证据的遗传流行病学支持个性化医疗,使早期预防策略和生活方式修改能够改善健康和寿命.
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