Nature:结合医疗和研究数据发现28种遗传病的证据

2020-10-17 haibei MedSci原创

据以往估计,约42-48%的严重发育障碍(DD)患者的蛋白质编码基因存在致病性新突变(DNM)。然而,尽管人们已经发现了数百个与DD相关的基因,但这些患者中的大多数仍未被诊断出来。

据以往估计,约42-48%的严重发育障碍(DD)患者的蛋白质编码基因存在致病性新突变(DNM)。然而,尽管人们已经发现了数百个与DD相关的基因,但这些患者中的大多数仍未被诊断出来。这表明,还有更多的DD相关基因有待发现。

现有的检测破坏性DNM的基因特异性富集的方法并没有纳入所有关于哪些变异更有可能与疾病相关的信息;错义突变和蛋白截断变异(PTVs)对蛋白功能的影响各不相同。已知的显性DD相关基因强烈富集在少数基因中,表现出对杂合子PTVs的强烈选择性约束。

为了确定额外的DD相关基因,我们需要通过增加样本大小和改进统计方法,来增加检测基因特异性富集的破坏性DNMs的可能性。在以前的致病性拷贝数变化的研究中,使用医疗保健数据一直是实现更大的样本量的关键。

最近,为了识别以前未被描述的与发育障碍相关的基因,研究人员整合了来自31,058名发育障碍患者父母-后代三人组的医疗和研究外显子序列数据,并开发了一个基于模拟的统计测试来识别基因特异性富集的新突变。

研究人员发现了285个与发育障碍显著相关的基因,其中包括28个之前未被证实与发育障碍相关的基因。虽然研究人员检测到了更多与发育障碍相关的基因,但蛋白质编码基因中过多的全新突变仍有很多未被解释。

建模结果表明,有超过1000个与发育障碍相关的基因尚未被描述,其中许多基因可能比目前已知的基因渗透力更低。研究人员获得临床诊断数据集对于完成发育障碍相关基因图谱至关重要。

 

原始出处:

Joanna Kaplanis et al. Evidence for 28 genetic disorders discovered by combining healthcare and research data. Nature (2020). 

https://www.nature.com/articles/s41586-020-2832-5

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    2021-06-15 liye789132251
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    2020-10-17 14686d88m59暂无昵称

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