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
1Bilkent University.
Research square
|March 31, 2025
概括
个人平均继承4.31种致病或可能致病的遗传变异,影响疾病倾向. 这项研究强调了遗传风险变异的流行及其对个性化医学和公共卫生的影响.
科学领域:
- 遗传学 是一个遗传学.
- 基因组医学是基因组医学.
- 人口健康 人口健康
背景情况:
- 调查不同人群中疾病倾向的遗传负担至关重要.
- 利用美国医学遗传学和基因组学学院 (ACMG) 的指导方针和大量人口变异数据库有助于变异分类.
- 开发了一种基于ACMG的新型自动变异分类工具,并应用于基因组聚合数据库 (gnomAD) 中730,947个个体的外体序列数据.
研究的目的:
- 量化大量人口队列中致病性和可能致病性遗传变异的负担.
- 识别与孟德尔条件相关的基因和可操作的基因型.
- 探索基于遗传数据的载体查和个性化药物的潜力.
主要方法:
- 来自3895个英格兰基因组学小组App基因的杆化等位基因频率数据.
- 使用基于ACMG的自动分类工具识别了致病性 (P) 和可能致病性 (LP) 变体.
- 在gnomAD.中分析了来自730,947个个体的外体序列数据.
主要成果:
- 确定了76,677种致病性变异和295,356种可能致病性变异,显著扩大了ClinVar提交的数量.
- 平均而言,个体携带4.31个P或LP变体,其中1.59个与孟德尔条件相容.
- 12个个体中有1个具有可操作的基因型,372个基因是载体查的候选者.
- 基因组第一方法揭示了各种类别中与疾病相关的基因型的高患病率,包括先天性,神经和血液/免疫疾病.
结论:
- 基于证据的遗传流行病学支持个性化医疗,用于预防策略和生活方式修改,以改善健康.
- 告知公众关于遗传性疾病风险变体的信息对于减少歧视和社会污名化至关重要.
- 大多数人携带生殖线风险变体,强调需要遗传素养和意识.
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