Genetics and Genomics

Researchers in the Centre for Genetics and Genomics have played a key role in developing large-scale sources of clinical and genomic data, including the UK Rare Kidney Disease (RaDaR) Registry and the 100,000 Genomes project. 

We use statistical, computational and laboratory-based tools to gain new insights into the biology underlying a range of disorders. This includes the discovery of novel monogenic disorders, such as EAST syndrome and CFHR5 nephropathy, as well as detecting other types of genetic association, across the full range of allele frequency and effect size, leading to new insights into a range of immune-mediated and developmental kidney diseases including membranous nephropathy, IgA nephropathy, nephrotic syndrome, Alport syndrome, kidney stones and posterior urethral valves.

We work closely with nephrology teams at the Royal Free Hospital and Great Ormond Street Hospital, and have strong links with the UK Kidney Association’s Rare Kidney Disease Registry (rarerenal.org) of which Professor Gale is the director. This is the largest registry of rare kidney diseases in the world and has provided significant insights into the clinical course and epidemiology of numerous rare kidney diseases.

Our researchers are experienced in the use of in vitro, in vivo, bioinformatic and statistical methods and we collaborate widely with other teams and institutions including sharing our expertise in genomic analyses beyond kidney diseases and we have strong ongoing collaborations with colleagues at UCL, the Francis Crick Institute and numerous other institutions worldwide.

Dr Omid Sadeghi-Alavijeh at APAM 2023

1. Sadeghi-Alavijeh O, Chan MMY, Moochhala SH, Genomics England Research Consortium, Howles S, Gale DP, Böckenhauer D (2023). Rare variants in the sodium-dependent phosphate transporter SLC34A3 explain missing heritability of urinary stone disease. Kidney International.

2. Downie ML, Gupta S, Voinescu C, Levine AP, Sadeghi-Alavijeh O, Dufek-Kamperis S ... Kleta R, Bockenhauer D, Stanescu HC, Gale DP (2023). Common Risk Variants in AHI1 Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome. Kidney International Reports.

3. Pitcher D, Braddon F, Hendry B, Mercer A, Osmaston K, Saleem MA, Steenkamp R, Wong K, Turner AN, Wang K, Gale DP, Barratt J (2023). Long-Term Outcomes in IgA Nephropathy. Clinical Journal of the American Society of Nephrology. 2023 Jun 1;18(6):727-738.

4. Chan MMY, Sadeghi-Alavijeh O, Stanescu HC, Kleta R, Bockenhauer D, Levine AP, Gale DP, et al. (2022). Diverse ancestry whole-genome sequencing association study identifies TBX5and PTK7 as susceptibility genes for posterior urethral valves. Elife. 2022 Sep 20;11:e74777.

5. Dixon PH, Levine AP, Chan MMY Gale DP et al. (2022). GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements. Nat Commun. 2022 Aug 17;13(1):4840.
6. Stubbs MJ, Coppo P, Levine AP, et al. (2021). Identification of a novel genetic locus associated with immune-mediated thrombotic thrombocytopenic purpura. Haematologica.
7. Kadkhodayi-Kholghi N, Gale DP, Perkins SJ, et al. (2020). The solution structure of the complement deregulator FHR5 reveals a compact dimer and provides new insights into CFHR5 nephropathy. Journal of Biological Chemistry, jbc.RA120.015132.
8. Turro E, Astle WJ, Megy K, et al. (2020). Whole-genome sequencing of patients with rare diseases in a national health system. Nature.

9. Levine, A.P. et al. (2020). Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy. J Am Soc Nephrol. 2020 Feb;31(2):365-373. 
10. Dufek, S. et al. (2019). Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome. Journal of the American Society of Nephrology. 2019 Aug;30(8):1375-1384.
11. Reichold, M. et al. (2018). Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure. Journal of the American Society of Nephrology.
12. Gale, D.P. et al. (2017). Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1. J Am Soc Nephrol.
13. Cabezas OR, Stanescu H, Patel V, Bockenhauer D, et al. (2017). Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2. Journal of the American Society of Nephrology.
14. Klootwijk ED, Reichold M, Bockenhauer D et al. (2014). Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome. New England Journal of Medicine, 370 129-138.
15. Stanescu, H.C. et al. (2011). Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. New England Journal of Medicine, 364 616-626.
16. Gale, D.P. et al. (2010). Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet, 376 (9743), 794-801.
17. Bockenhauer, D. et al. (2009). Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. New England Journal of Medicine, 360 (19), 1960-1970.