A platform for experimental precision medicine: The extended BXD mouse family.

A platform for experimental precision medicine: The extended BXD mouse family.
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DOI:
10.1016/j.cels.2020.12.002
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发表时间:
2021-03-17
期刊:
影响因子:
9.3
通讯作者:
Williams RW
Williams RW
中科院分区:
生物学1区
文献类型:
--
作者:
Ashbrook DG;Arends D;Prins P;Mulligan MK;Roy S;Williams EG;Lutz CM;Valenzuela A;Bohl CJ;Ingels JF;McCarty MS;Centeno AG;Hager R;Auwerx J;Lu L;Williams RW

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精准医学的挑战是对 DNA 变异、表型、发育、环境和治疗之间复杂的相互作用进行建模。我们通过将 BXD 小鼠家族扩展到 140 个完全同基因品系来应对这一挑战,为精准医疗创建了一个独特且强大的模型。该家族分离了 600 万种常见 DNA 变体,这一水平超过了许多人类群体。由于每个成员都可以复制,因此可以以高功效和精确度绘制可遗传性状。目前的 BXD 表型覆盖范围无与伦比,包括大量组学数据和数千个数量性状。 BXD 可以通过单代杂交扩展到多达 19,460 个同基因 F1 后代,并且这个扩展的 BXD 家族是测试因果模型和预测验证的有效平台。 BXD 是实验精准医学领域独特的核心资源。 Ashbrook 等人将 BXD 家族扩展到 140 个菌株,为翻译精度和预测生物学提供了新工具,并扩展了超过 100 个组学数据集和超过 7500 个现有经典表型的深层表型的有用性。通过使用新的基因型、更新的模型和更多的菌株,它们显示出更高的精度和功效。
The challenge of precision medicine is to model complex interactions among DNA variants, phenotypes, development, environments, and treatments. We address this challenge by expanding the BXD family of mice to 140 fully isogenic strains, creating a uniquely powerful model for precision medicine. This family segregates for 6 million common DNA variants—a level that exceeds many human populations. Because each member can be replicated, heritable traits can be mapped with high power and precision. Current BXD phenomes are unsurpassed in coverage and include much omics data and thousands of quantitative traits. The BXDs can be extended by a single-generation cross to as many as 19,460 isogenic F1 progeny, and this extended BXD family is an effective platform for testing causal modeling and for predictive validation. The BXDs are a unique core resource for the field of experimental precision medicine. Ashbrook et al., have expanded the BXD family to 140 strains, providing a new tool for translational precision and predictive biology, and extended the usefulness of the deep phenome of >100 omics datasets and >7500 classical phenotypes already available. They show increased precision and power by using new genotypes, updated models and more strains.
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