Genetic diseases cause numerous complex and intractable pathologies. DNA sequences encoding each human's complexity and many disease risks are contained in the mitochondrial genome, nuclear genome, and microbial metagenome. Diagnosis of these diseases has unified around applications of next-generation DNA sequencing. However, translating specific genetic diagnoses into targeted genetic therapies remains a central goal. To date, genetic therapies have fallen into three broad categories: bulk replacement of affected genetic compartments with a new exogenous genome, nontargeted addition of exogenous genetic material to compensate for genetic errors, and most recently, direct correction of causative genetic alterations using gene editing. Generalized methods of diagnosis, therapy, and reagent delivery into each genetic compartment will accelerate the next generations of curative genetic therapies. We discuss the structure and variability of the mitochondrial, nuclear, and microbial metagenomic compartments, as well as the historical development and current practice of genetic diagnostics and gene therapies targeting each compartment.

中文翻译：

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遗传病和治疗。

遗传疾病会导致许多复杂和棘手的病症。编码每个人的复杂性和许多疾病风险的 DNA 序列包含在线粒体基因组、核基因组和微生物宏基因组中。这些疾病的诊断已统一围绕下一代 DNA 测序的应用。然而，将特定的基因诊断转化为靶向基因治疗仍然是一个中心目标。迄今为止，基因疗法已分为三大类：用新的外源基因组大量替换受影响的基因区室，非靶向添加外源遗传物质以补偿遗传错误，以及最近使用基因编辑直接纠正致病基因改变。诊断、治疗的一般方法，将试剂输送到每个基因区室将加速下一代治疗性基因疗法的发展。我们讨论了线粒体、核和微生物宏基因组区室的结构和变异性，以及针对每个区室的基因诊断和基因治疗的历史发展和当前实践。