在功能相关基因的基因组多样性改变神经发育与瘤风险在具有生殖线PTEN变异的个体神经发育与瘤风险
Charis Eng1, Adriel Kim1, Lamis Yehia1
1Cleveland Clinic.
Research square
|January 3, 2024
概括
生殖系PTEN变种增加了癌症和神经发育障碍 (NDD) 的风险,包括自闭症谱系障碍 (ASD). 特定基因的同卵性增加可能解释了这些不同的结果,提供了一个新的预测模型.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 神经发育障碍 神经发育障碍
- 癌症生物学 癌症生物学
背景情况:
- 生殖系PTEN变体 (PHTS) 与癌症和神经发育障碍 (NDD) 的风险增加有关,例如自闭症谱系障碍 (ASD).
- 对于PHTS患者广泛的表型变异的根本原因尚未完全理解.
- 这项研究调查了基因组多样性减少的作用,特别是增加的同卵性,作为潜在的病因因素.
研究的目的:
- 探索这种假设,即同卵性增加有助于在具有生殖线PTEN变异的个体中观察到的表型多样性.
- 为了确定与PHTS患者的NDD/ASD与癌症相关的特定遗传途径和基因.
- 评估同卵性负担对NDD/ASD结果的预测价值.
主要方法:
- 对来自376名欧洲血统PHTS患者的生殖系遗传数据的全面分析.
- 分析的重点是与特定生物过程相关的基因中同卵性常见和超罕见变异的丰富.
- 途径分析和崩分析被用来识别相关的生物途径和潜在的修饰基因.
- 开发和验证一个包含同卵性负担的预测模型.
主要成果:
- 在PHTS-NDD和PHTS-ASD组中的炎症和分化/染色体调节基因中,同卵性常见变异的显著丰富.
- 确定了与NDD/ASD相关的途径,包括神经炎症和突触生成.
- 在PHTS癌症组的细胞死亡调节基因中发现了同卵性超罕见变异的丰富.
- 在一个经过验证的模型中,同卵性负担证明了作为ASD与癌症结果的预测指标的良好表现.
结论:
- 在特定的基因组中增加的同胞性与具有生殖线PTEN变异的个体中与不同的表型 (NDD/ASD与癌症) 有关.
- 与炎症,神经发育和细胞死亡相关的遗传途径与PHTS相关的表型变异性有关.
- 同卵性负担作为一种潜在的预测生物标志物,用于区分NDD/ASD与PHTS患者的癌症结局.
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