Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.

中文翻译：

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国际小鼠表型联盟从 3,328 个基因敲除中发现疾病模型。

尽管下一代测序已经彻底改变了将变异与人类疾病相关联的能力，但由于对大多数基因的功能和病理生物学机制缺乏了解，诊断率和新疗法的开发仍然受到限制。为了应对这一挑战，国际小鼠表型分析协会正在通过一系列广泛的标准化表型分析测试来表征跨不同生物系统的新敲除小鼠品系，从而创建一个基因组和表型范围的基因功能目录。所有的老鼠都将随时可供生物医学界使用。分析前 3,328 个基因确定了 360 种疾病的模型，包括据我们所知的第一个模型，用于 C 型 Bernard-Soulier、Bardet-Biedl-5 和 Gordon Holmes 综合征。我们 90% 的表型注释是新颖的，