Translational Gastroenterology Unit, University of Oxford, UK; Department of Paediatrics, University of Oxford, UK.
Program in Cell Biology, Research Institute, Hospital for Sick Children, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada; SickKids Inflammatory Bowel Disease Centre and Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada.
Trends Genet. 2017 Sep;33(9):629-641. doi: 10.1016/j.tig.2017.06.008. Epub 2017 Jul 26.
Genomic technologies inform the complex genetic basis of polygenic inflammatory bowel disease (IBD) as well as Mendelian disease-associated IBD. Aiming to diagnose patients that present with extreme phenotypes due to monogenic forms of IBD, genomics has progressed from 'orphan disease' research towards an integrated standard of clinical care. Advances in diagnostic clinical genomics are increasingly complemented by pathway-specific therapies that aim to correct the consequences of genetic defects. This highlights the exceptional potential for personalized precision medicine. IBD is nevertheless a challenging example for genomic medicine because the overall fraction of patients with Mendelian defects is low, the number of potential candidate genes is high, and interventional evidence is still emerging. We discuss requirements and prospects of explanatory and predictive clinical genomics in IBD.
基因组学技术为多基因炎症性肠病（IBD）以及孟德尔疾病相关的 IBD 的复杂遗传基础提供了信息。由于单基因形式的 IBD 导致的极端表型，旨在诊断患者，基因组学已从“孤儿病”研究发展为综合临床护理标准。诊断临床基因组学的进步越来越多地被旨在纠正遗传缺陷后果的特定途径的治疗方法所补充。这突出了个性化精准医学的特殊潜力。然而，IBD 是基因组医学的一个具有挑战性的例子，因为孟德尔缺陷患者的总体比例较低，潜在候选基因数量较多，干预证据仍在不断涌现。我们讨论了 IBD 中解释性和预测性临床基因组学的要求和前景。
