Centre for Genetics and Genomics

We use bioinformatic and functional biology approaches to study genetic kidney disease

Use of genetic technologies such as genotyping and large-scale whole genome sequencing has allowed researchers in the Centre for Genetics and Genomics to gain new insights into the biology underlying a range of kidney diseases. This includes discovery of novel monogenic disorders, such as EAST syndrome and CFHR5 nephropathy, as well as providing key insights into the causes and contributors to a range of more common kidney diseases such as membranous nephropathy, IgA nephropathy and nephrotic syndrome.

Researchers in the Centre are experienced in the use of in vitro, in vivo and bioinformatic methods to study the mechanisms by which genetic variation contributes to disease, including the development of potential novel therapies.

Notable publications from the centre include (full list here and below):

1. 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.   Diverse ancestry whole-genome sequencing association study identifies TBX5and PTK7 as susceptibility genes for posterior urethral valves. Elife. 2022 Sep 20;11:e74777. doi: 10.7554/eLife.74777. PMID: 36124557
2. Dixon PH, Levine AP, Cebola I, Chan MMY, Amin AS, Aich A, Mozere M, Maude H, Mitchell AL, Zhang J; NIHR BioResource; Genomics England Research Consortium Collaborators, Chambers J, Syngelaki A, Donnelly J, Cooley S, Geary M, Nicolaides K, Thorsell M, Hague WM, Estiu MC, Marschall HU, Gale DP, Williamson C. GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements. Nat Commun. 2022 Aug 17;13(1):4840. doi: 10.1038/s41467-022-29931-z. PMID: 35977952
3. Stubbs, M.J., Coppo, P., Cheshire, C., Veyradier, A., Dufek, S., Levine, A.P., ...Hubank, M. (2021). Identification of a novel genetic locus associated with immune mediated thrombotic thrombocytopenic purpura.. Haematologica, doi:10.3324/haematol.2020.274639
4. Kadkhodayi-Kholghi, N., Bhatt, J.S., Gor, J., McDermott, L.C., Gale, D.P., Perkins, S.J. (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. doi:10.1074/jbc.ra120.015132
5. Turro, E., Astle, W.J., Megy, K., Gräf, S., Greene, D., Shamardina, O., ...Thys, C. (2020). Whole-genome sequencing of patients with rare diseases in a national health system. Nature, doi:10.1038/s41586-020-2434-2
6. 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. doi: 10.1681/ASN.2019040433.
7. Dufek, S. et al. (2019). Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome. J Am Soc Nephrol. 2019 Aug;30(8):1375-1384. doi: 10.1681/ASN.2018101054
8. Reichold, M. et al. (2018). Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure. Journal of the American Society of Nephrology : JASN, doi:10.1681/asn.2017111179
9. Gale, D.P. et al. (2017). Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1. J Am Soc Nephrol, doi:10.1681/ASN.2016091043
10. Cabezas, O.R. et al. (2017). Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2. Journal of the American Society of Nephrology, doi:10.1681/ASN.2016121312
11. Klootwijk, E.D. et al. (2014). Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome. New England Journal of Medicine, 370 129-138
12. 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. doi:10.1056/NEJMoa1009742
13. 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. doi:10.1016/S0140-6736(10)60670-8
14. Bockenhauer, D. et al. (2009). Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. New England Journal of Medicine, 360 (19), 1960-1970.

Faculty

	Professor Daniel Gale	Head of Centre Adult nephrologist Complement mediated disease Polycystic Kidney Disease Alport Syndrome Unexplained Familial kidney failure
	Professor Detlef Bockenhauer	Deputy Head Paedatric nephrologist Inherited kidney diseases Tubulopathies Renal physiology
	Professor Robert Kleta	Director of UCL Division of Medicine Paediatric nephrologist  Rare metabolic and renal disorders
	Dr Horia Stanescu	Lecturer genetic / genomic / multi-omic analysis bioinformatics /computational biology expression regulation evolutionary pathogenesis
	Dr Anselm Zdebik
	Professor Patricia Wilson	Polycystic kidney disease
Centre Staff
	Dr Omid Sadeghi-Alavijeh	MRC Doctoral Fellow Adult nephrology trainee Computational biology in rare kidney disorders Polycystic kidney disease  100,000 genomes project
	Dr Melanie Chan	KRUK Doctoral Fellow Adult nephrology trainee Computational biology in rare kidney disorders Congential abnormalities of the kidney and urinary tract (CAKUT) 100,000 genomes project
	Dr Sanjana Gupta	PhD Student Adult nephrology trainee Bioinformatics  Membranous nephropathy
	Dr Adam Levine	Research Associate Histopathology trainee Computational biology  Genetics and pathogenesis of IBD Genetics of membranoproliferative glomerulonephritis Genetic variation in tissue morphology
	Catalin Voinescu	Computational Scientist
	Dr Vaksha Patel	Lab Manager Proteomics in rare kidney disease Phosphoproteomics Bioinformatics
	Dr Evgenia Preka	Clinical Research Fellow in Renal Genomics  Paediatric nephrologist Epidemiology in rare renal diseases  Biostatistics
	Dr Joanna Smith	Postdoctoral Research Fellow Protein Biochemistry Molecular Biology Complement mediated kidney disease
	Joshua Carmichael	MB/PhD Student Structural immunology of CFHR5 Complement mediated kidney disease
	Gabriel Doctor	Clinical Research Fellow/PhD Student Genomics of immune-mediated kidney disease
	David Pitcher	Statistician/PhD student Rare Renal Disease Registry Natural history and outcomes in rare kidney diseases
	Katie Wong	Clinical Research Fellow/PhD student Rare Renal Disease Registry Epidemiology, genetics and outcomes in rare kidney diseases
Centre Alumni
Dr Mallory Downie
Dr Sergio Camilo Lopez Garcia
Dr Matthew Stubbs