Elliott Mark D, Rasouly Hila Milo, Gharavi Ali G
Division of Nephrology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; email:
Center for Precision Medicine and Genomics, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Annu Rev Med. 2023 Jan 27;74:353-367. doi: 10.1146/annurev-med-042921-101813. Epub 2022 Nov 14.
Hundreds of different genetic causes of chronic kidney disease are now recognized, and while individually rare, taken together they are significant contributors to both adult and pediatric diseases. Traditional genetics approaches relied heavily on the identification of large families with multiple affected members and have been fundamental to the identification of genetic kidney diseases. With the increased utilization of massively parallel sequencing and improvements to genotype imputation, we can analyze rare variants in large cohorts of unrelated individuals, leading to personalized care for patients and significant research advancements. This review evaluates the contribution of rare disorders to patient care and the study of genetic kidney diseases and highlights key advancements that utilize new techniques to improve our ability to identify new gene-disease associations.
目前已确认有数百种不同的慢性肾病遗传病因，虽然这些病因单独来看很罕见，但总体而言，它们在成人和儿童疾病中都是重要的致病因素。传统遗传学方法严重依赖于识别有多个患病成员的大家庭，并且对于遗传性肾病的识别至关重要。随着大规模平行测序的更多应用以及基因型填充技术的改进，我们能够分析大量无亲缘关系个体中的罕见变异，从而为患者提供个性化护理并取得重大研究进展。本综述评估了罕见疾病对患者护理和遗传性肾病研究的贡献，并强调了利用新技术提高我们识别新基因 - 疾病关联能力的关键进展。
