PDF(Pubmed)
Abstract：
OBJECTIVE: Existing resources that characterize the essentiality status of genes are based on either proliferation assessment in human cell lines, viability evaluation in mouse knockouts, or constraint metrics derived from human population sequencing studies. Several repositories document phenotypic annotations for rare disorders; however, there is a lack of comprehensive reporting on lethal phenotypes.
METHODS: We queried Online Mendelian Inheritance in Man for terms related to lethality and classified all Mendelian genes according to the earliest age of death recorded for the associated disorders, from prenatal death to no reports of premature death. We characterized the genes across these lethality categories, examined the evidence on viability from mouse models and explored how this information could be used for novel gene discovery.
RESULTS: We developed the Lethal Phenotypes Portal to showcase this curated catalog of human essential genes. Differences in the mode of inheritance, physiological systems affected, and disease class were found for genes in different lethality categories, as well as discrepancies between the lethal phenotypes observed in mouse and human.
CONCLUSIONS: We anticipate that this resource will aid clinicians in the diagnosis of early lethal conditions and assist researchers in investigating the properties that make these genes essential for human development.
METHODS: We queried Online Mendelian Inheritance in Man for terms related to lethality and classified all Mendelian genes according to the earliest age of death recorded for the associated disorders, from prenatal death to no reports of premature death. We characterized the genes across these lethality categories, examined the evidence on viability from mouse models and explored how this information could be used for novel gene discovery.
RESULTS: We developed the Lethal Phenotypes Portal to showcase this curated catalog of human essential genes. Differences in the mode of inheritance, physiological systems affected, and disease class were found for genes in different lethality categories, as well as discrepancies between the lethal phenotypes observed in mouse and human.
CONCLUSIONS: We anticipate that this resource will aid clinicians in the diagnosis of early lethal conditions and assist researchers in investigating the properties that make these genes essential for human development.
摘要：
目的：表征基因重要性状态的现有资源是基于人类细胞系中的任一增殖评估，小鼠敲除中的生存能力评估，或来自人群测序研究的约束指标。几个存储库记录了罕见疾病的表型注释，然而，缺乏关于致命表型的全面报告。
方法：我们向在线孟德尔遗传人查询了与致死性相关的术语，并根据相关疾病的最早死亡年龄对所有孟德尔基因进行了分类。从产前死亡到没有过早死亡的报告。我们对这些致死性类别的基因进行了表征，研究了来自小鼠模型的生存力的证据，并探索了这些信息如何用于新基因发现。
结果：我们开发了致命表型门户来展示这个人类必需基因的精选目录。继承方式的差异，对于不同致死性类别的基因，以及在小鼠和人类中观察到的致死表型之间的差异，发现了受影响的生理系统和疾病类别。
结论：我们预计该资源将帮助临床医生诊断早期致死性疾病，并帮助研究人员研究使这些基因对人类发育至关重要的特性。
方法：我们向在线孟德尔遗传人查询了与致死性相关的术语，并根据相关疾病的最早死亡年龄对所有孟德尔基因进行了分类。从产前死亡到没有过早死亡的报告。我们对这些致死性类别的基因进行了表征，研究了来自小鼠模型的生存力的证据，并探索了这些信息如何用于新基因发现。
结果：我们开发了致命表型门户来展示这个人类必需基因的精选目录。继承方式的差异，对于不同致死性类别的基因，以及在小鼠和人类中观察到的致死表型之间的差异，发现了受影响的生理系统和疾病类别。
结论：我们预计该资源将帮助临床医生诊断早期致死性疾病，并帮助研究人员研究使这些基因对人类发育至关重要的特性。
