Genomics, Development and Rare Diseases

Our work

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

Current projects

1. Structure and function of CFHR5 and its role in health and disease
2. Immunogenetics in idiopathic nephrotic syndrome
3. Genomics of polycystic kidney disease
4. Genomics of posterior urethral valves
5. Genomics of renal stone diseases
6. Genomics of Alport Syndrome
7. Paleogenomics of idiopathic membranous nephropathy.

The Gale Group

Centre alumni

• Professor Detlef Bockenhauer
• Professor Robert Kleta
• Dr Evgenia Preka
• Dr Mallory Downie
• Dr Sanjana Gupta
• Dr Sergio Camilo Lopez Garcia
• Dr Matthew Stubbs
• Dr Stephanie Dufek

Selected Publications 

1. Sadeghi-Alavijeh O, Chan MM, Doctor GT ... Stanescu HC, Bockenhauer D ... Levine AP, Gale DP (2024). Quantifying variant contributions in cystic kidney disease using national-scale whole genome sequencing. J Clin Invest. 2024 Aug 27: e181467.
2. Gale DP, Gross O, Wang F, et al (2024). A Randomized Controlled Clinical Trial Testing Effects of Lademirsen on Kidney Function Decline in Adults with Alport Syndrome. Clin J Am Soc Nephrol. 2024 Aug 1;19(8): 995-1004.
3. Voinescu CD, Mozere M, Genovese G, Downie ML, Gupta S, Gale DP, Bockenhauer D, Kleta R, Arcos-Burgos M, Stanescu HC (2024). A Neanderthal haplotype introgressed into the human genome confers protection against membranous nephropathy. Kidney Int. 2024 Apr;105(4): 791-798.
4. Wong K, Pitcher D, Braddon F ... Wilson P ... Bockenhauer D, Bramham K, Gale DP; RaDaR consortium (2024). Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort. Lancet. 2024 Mar 30;403(10433): 1279-1289.
5. Sadeghi-Alavijeh O, Chan MMY ... Gale DP, Böckenhauer D (2023). Rare variants in the sodium-dependent phosphate transporter gene SLC34A3 explain missing heritability of urinary stone disease. Kidney Int. 2023 Nov;104(5): 975-984.
6. 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.
7. Pitcher D, Braddon F ... Wong K, Turner AN, Wang K, Gale DP, et al (2023). Long-Term Outcomes in IgA Nephropathy. Clin J Am Soc Nephrol. 2023 Jun 1;18(6): 727-738.
8. 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.
9. 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.
10. Stubbs MJ, Coppo P ... Dufek S, Levine AP ... Kleta R, Gale DP, Stanescu H, Scully MA (2022). Identification of a novel genetic locus associated with immune-mediated thrombotic thrombocytopenic purpura. Haematologica. 2022 Mar 1;107(3):574-582.
11. Kadkhodayi-Kholghi N, Bhatt JS ... Gale DP, Perkins SJ (2020). The solution structure of the complement deregulator FHR5 reveals a compact dimer and provides new insights into CFHR5 nephropathy. J Biol Chem. 2020 Nov 27;295(48): 16342-16358. 
12. Turro E, Astle WJ, Megy K ... Gale DP, et al (2020). Whole-genome sequencing of patients with rare diseases in a national health system. Nature. 2020 Jul;583(7814): 96-102.
13. Levine AP, Chan MMY, Sadeghi-Alavijeh O ... Gale DP (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.
14. Dufek S, Cheshire C, Levine AP, Trompeter RS, Issler N, Stubbs M, Mozere M, Gupta S, Klootwijk E, Patel V ... Gale DP, Stanescu HC, Kleta R, Bockenhauer D (2019). Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome. J Am Soc Nephrol. 2019 Aug;30(8): 1375-1384.
15. Reichold M, Klootwijk ED ... Stanescu HC, Dumitriu S, Iancu D, Patel V ... Gale DP ... Bockenhauer D, Lichter-Konecki U, Gahl WA, Unwin RJ, Warth R, Kleta R (2018). Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure. J Am Soc Nephrol. 2018 Jul;29(7): 1849-1858.
16. Gale DP, Molyneux K, Wimbury D, Higgins P, Levine AP, Caplin B, Ferlin A, Yin P, Nelson CP, Stanescu H, Samani NJ, Kleta R, et al (2017). Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1. J Am Soc Nephrol. 2017 Jul;28(7): 2158-2166.
17. Cabezas OR, Flanagan SE, Stanescu H, García-Martínez E ... Patel V ... Wilson P, Guay-Woodford L, Kleta R, Hussain K, Ellard S, Bockenhauer D (2017). Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2. J Am Soc Nephrol. 2017 Aug;28(8):  2529-2539.
18. Klootwijk ED, Reichold M, Helip-Wooley A ... Stanescu HC, Bockenhauer D ... Kleta R (2014). Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome. N Engl J Med. 2014 Jan 9;370(2): 129-38.
19. Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, Voinescu C ... Kleta R (2011). Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med. 2011 Feb 17;364(7): 616-26.
20. Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, et al (2010). Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet. 2010 Sep 4;376(9743): 794-801.

Facilities

The Centre for Genetics and Genomics has wet lab facilities well equipped for molecular biology, protein biochemistry, cell culture, histology/IHC and in vivo experimentation.

We run our own secure, high performance data server and can access the UCL Advanced Research Computing Centre resources.

Related programmes

Our members contribute to the MBBS, iBSc, BSc and master's degrees within the Division of Medicine. We provide MSc/MRes research project supervision. We also have an established track record in providing high-quality training to PhD students interested in epidemiological, genomic, proteomic and immunological aspects of kidney disease.