Elucidating the genetic architecture of cystic kidney disease using whole-genome sequencing

使用全基因组测序阐明囊性肾病的遗传结构

• 批准号: MR/S021329/1
• 负责人: Omid Sadeghi-Alavijeh
• 金额: $ 29.09万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS021329%2F1
• 关键词: Elucidating; genetic; architecture; cystic; kidney

Cystic kidney diseases, including polycystic kidney disease, account for a significant proportion of kidney failure in the UK, often run in families and usually result from a change in a gene (instructions that organisms use to establish and maintain healthy function). However, not everyone with cystic kidney disease will develop kidney failure and the reasons for this variability are poorly understood.This project will use data from sequencing the whole genomes (i.e. all the genes) of over 1200 families with cystic kidney disease along with detailed clinical information, such as which other organs are affected and whether and when kidney failure developed. In over 300 of the families, detailed information will be available on whether and how identifying the genetic change influenced clinical management. This will reveal the utility and benefits of genome sequencing to diagnose the cause of cystic kidney disease in patients and will provide new insights into the consequences and severity of each type of gene change. Previous studies have shown that in around 10% of families with polycystic kidney disease the gene responsible cannot be identified. By using comparisons with genome sequences from large numbers of people without kidney disease, this project is uniquely placed to identify changes in genes not previously thought to be involved in cystic kidney disease, providing new insights into how kidney cysts form and develop, potentially leading to new treatments.

囊性肾脏疾病，包括多囊性肾脏疾病，在英国肾衰竭中占很大比例，通常在家族中遗传，通常由基因变化引起（生物体用来建立和维持健康功能的指令）。然而，并不是每个患有囊性肾病的人都会发展为肾衰竭，这种差异的原因尚不清楚。该项目将使用来自1200多个囊性肾病家族的全基因组（即所有基因）测序数据以及详细的临床信息，例如哪些其他器官受到影响以及是否以及何时发生肾衰竭。在超过300个家庭中，将获得关于确定遗传变化是否以及如何影响临床管理的详细信息。这将揭示基因组测序在诊断患者囊性肾病病因方面的效用和益处，并将为每种基因变化的后果和严重程度提供新的见解。先前的研究表明，在大约10%的多囊肾病家庭中，无法确定致病基因。通过与大量没有肾脏疾病的人的基因组序列进行比较，该项目具有独特的地位，可以识别以前未被认为与囊性肾病有关的基因变化，为肾囊肿的形成和发展提供新的见解，可能会导致新的治疗方法。

项目成果

Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves.

• DOI: 10.7554/elife.74777
• 发表时间: 2022-09-20
• 期刊: eLife
• 影响因子: 7.7
• 作者: Chan MMY;Sadeghi-Alavijeh O;Lopes FM;Hilger AC;Stanescu HC;Voinescu CD;Beaman GM;Newman WG;Zaniew M;Weber S;Ho YM;Connolly JO;Wood D;Maj C;Stuckey A;Kousathanas A;Genomics England Research Consortium;Kleta R;Woolf AS;Bockenhauer D;Levine AP;Gale DP
• 通讯作者: Gale DP

Common Risk Variants in AHI1 Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome.

• DOI: 10.1016/j.ekir.2023.05.018
• 发表时间: 2023-08
• 期刊: KIDNEY INTERNATIONAL REPORTS
• 影响因子: 6
• 作者: Downie, Mallory L.;Gupta, Sanjana;Voinescu, Catalin;Levine, Adam P.;Sadeghi-Alavijeh, Omid;Dufek-Kamperis, Stephanie;Cao, Jingjing;Christian, Martin;Kari, Jameela A.;Thalgahagoda, Shenal;Ranawaka, Randula;Abeyagunawardena, Asiri;Gbadegesin, Rasheed;Parekh, Rulan;Kleta, Robert;Bockenhauer, Detlef;Stanescu, Horia C.;Gale, Daniel P.
• 通讯作者: Gale, Daniel P.

Genotype-phenotype correlations for COL4A3-COL4A5 variants resulting in Gly substitutions in Alport syndrome.

• DOI: 10.1038/s41598-022-06525-9
• 发表时间: 2022-02-17
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Gibson JT;Huang M;Shenelli Croos Dabrera M;Shukla K;Rothe H;Hilbert P;Deltas C;Storey H;Lipska-Ziętkiewicz BS;Chan MMY;Sadeghi-Alavijeh O;Gale DP;Genomics England Research Consortium;Cerkauskaite A;Savige J
• 通讯作者: Savige J

Primer on Nephrology

肾脏病学入门

• DOI: 10.1007/978-3-030-76419-7_1
• 发表时间: 2022
• 作者: Khosravi M

Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.

• DOI: 10.1007/s00467-022-05789-7
• 发表时间: 2023-06
• 期刊: Pediatric nephrology (Berlin, Germany)