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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遗传疾病和治疗。

遗传疾病导致许多复杂而棘手的病理。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，核基因组和微生物基因组中。这些疾病的诊断已围绕下一代DNA测序的应用进行了统一。然而，将特定的遗传诊断转化为靶向的遗传疗法仍然是中心目标。迄今为止，遗传疗法已分为三大类：用新的外源基因组大量替代受影响的遗传区室；无目标地添加外源遗传物质以补偿遗传错误；以及最近，通过基因编辑直接纠正因果遗传改变。通用的诊断，治疗方法，而且将试剂输送到每个基因区室将加速下一代治愈性基因治疗的发展。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遗传诊断和基因疗法的历史发展和当前实践。