Genomic technologies, such as targeted, exome and short-read genome sequencing approaches, have revolutionized the care of patients with rare genetic diseases. However, more than half of patients remain without a diagnosis. Emerging approaches from research-based settings such as long-read genome sequencing and optical genome mapping hold promise for improving the identification of disease-causal genetic variants. In addition, new omic technologies that measure the transcriptome, epigenome, proteome or metabolome are showing great potential for variant interpretation. As genetic testing options rapidly expand, the clinical community needs to be mindful of their individual strengths and limitations, as well as remaining challenges, to select the appropriate diagnostic test, correctly interpret results and drive innovation to address insufficiencies. If used effectively — through truly integrative multi-omics approaches and data sharing — the resulting large quantities of data from these established and emerging technologies will greatly improve the interpretative power of genetic and genomic diagnostics for rare diseases.

基因组技术，例如靶向、外显子组和短读长基因组测序方法，彻底改变了罕见遗传病患者的护理。然而，超过一半的患者仍未得到诊断。基于研究的新兴方法，例如长读长基因组测序和光学基因组图谱，有望改善致病遗传变异的识别。此外，测量转录组、表观基因组、蛋白质组或代谢组的新组学技术在变异解释方面显示出巨大的潜力。随着基因检测选择的迅速扩大，临床界需要注意各自的优势和局限性，以及仍然存在的挑战，以选择适当的诊断测试，正确解释结果并推动创新以解决不足。如果通过真正综合的多组学方法和数据共享得到有效利用，这些现有技术和新兴技术所产生的大量数据将大大提高罕见疾病遗传和基因组诊断的解释能力。