Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias.
Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias.
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DOI：
10.3389/fphys.2020.613559
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发表时间：
2020
影响因子：
4
通讯作者：
Andolfo I
中科院分区：
文献类型：
--
作者：
Russo R;Marra R;Rosato BE;Iolascon A;Andolfo I
遗传性贫血是一组相对异质性的疾病，可以表现出广泛的临床和遗传异质性，这常常妨碍正确的临床诊断。这些疾病的经典诊断工作流程通常从家庭和个人史分析开始，然后进行生化和形态学评估，最后以基因检测结束。然而，诊断框架最近发生了变化，基因检测现在是这些患者鉴别诊断的合适方法。这种基因检测有多种方法，选择哪种方法取决于表型、遗传异质性和基因大小。对于表现出完整表型的患者，仍然建议进行单基因检测。然而，遗传分析现在包括下一代测序，它通常基于定制设计的靶向面板和全外显子组测序。新一代测序的使用还可以识别新的致病基因，以及改变遗传性贫血疾病严重程度的多基因条件和遗传因素。在研究领域，全基因组测序可用于识别非编码致病突变，这可能解释转录因子占据位点和顺式调控元件的破坏。此外，高通量测序技术的进步现已导致染色质结构（称为拓扑关联域）的全基因组分析的鉴定。这些代表了一种复发性疾病机制，使基因暴露于不适当的调控元件中，导致基因表达错误。本综述重点关注遗传性贫血的诊断和研究面临的挑战，并指出其优点和缺点。最后，我们考虑了在这个精准医疗时代使用下一代测序技术的未来前景。
The hereditary anemias are a relatively heterogeneous set of disorders that can show wide clinical and genetic heterogeneity, which often hampers correct clinical diagnosis. The classical diagnostic workflow for these conditions generally used to start with analysis of the family and personal histories, followed by biochemical and morphological evaluations, and ending with genetic testing. However, the diagnostic framework has changed more recently, and genetic testing is now a suitable approach for differential diagnosis of these patients. There are several approaches to this genetic testing, the choice of which depends on phenotyping, genetic heterogeneity, and gene size. For patients who show complete phenotyping, single-gene testing remains recommended. However, genetic analysis now includes next-generation sequencing, which is generally based on custom-designed targeting panels and whole-exome sequencing. The use of next-generation sequencing also allows the identification of new causative genes, and of polygenic conditions and genetic factors that modify disease severity of hereditary anemias. In the research field, whole-genome sequencing is useful for the identification of non-coding causative mutations, which might account for the disruption of transcriptional factor occupancy sites and cis-regulatory elements. Moreover, advances in high-throughput sequencing techniques have now resulted in the identification of genome-wide profiling of the chromatin structures known as the topologically associating domains. These represent a recurrent disease mechanism that exposes genes to inappropriate regulatory elements, causing errors in gene expression. This review focuses on the challenges of diagnosis and research into hereditary anemias, with indications of both the advantages and disadvantages. Finally, we consider the future perspectives for the use of next-generation sequencing technologies in this era of precision medicine.
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影响因子：
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