Genetic variation is the fundamental basis of inherited disease and acquired diseases such as cancer. Current technologies allow us to investigate diseases where only one or a small number of variants of genes are altered e.g CF or Huntingtons disease. With inherited nephrotic syndrome (NS) it is now known that at least several dozen different genes could be altered, and we know almost nothing about how different alterations affect disease severity or response to treatment.
Recent advances in sequencing technologies are likely to revolutionalize medical diagnostics in both inherited and acquired disease. Using massively parallel sequencing – otherwise known as Next Generation Sequencing, and ever advancing bioinformatics platforms, we can now reliably sequence and analyse huge portions of the human genome. These platforms generate data on all the genetic variation potentially associated with NS, leading to the isolation of novel genes. The University of Bristol has one of these platforms, the Illumina GA2 within its genome research facility.
A key component of understanding the genetic basis of disease is a tightly defined and phenotyped cohort of patients. The project seeks to evaluate the application of targeted Next Generation sequencing technology to acquired and inherited NS gene pathways using such a cohort of patients, carefully collected as part of RADAR, the newly established renal rare disease registry 1-4. We aim to assess the extent of genetic variation in patients with NS, and discover new candidate genes. Furthermore we will use adenoviral gene therapy technology to correct genetic defects in the target cell, the podocyte. This work will further the knowledge of genetic pathways of NS and contribute to the development of improved genetic testing and new therapy for patients with these diseases
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 Agnieszka Bierzynska1 KS, Philip Dean3, Elizabeth Colby1, Caroline Jones4, Carol D. Inward1, Hugh J. McCarthy1, Michael A. Simpson5, Graham Lord2, Maggie Williams3, Gavin I. Welsh1, Ania B. Koziell2, Moin A. Saleem on behalf of RADAR the UK SRNS Study Group: MAGI-2 mutations are responsible for Congenital Nephrotic Syndrome. Am J Hum Genet 2016.
 Agnieszka Bierzynska HJM, Katrina Soderquest, Ethan S. Sen, Elizabeth Colby, Wen Y. Ding, Marwa M Nabhan, Larissa Kerecuk, Shivram Hegde, David Hughes, Stephen Marks, Sally Feather, Caroline Jones, Nicholas J A Webb, Milos Ognjanovic, Martin Christian Rodney D Gilbert, Manish D. Sinha, Graham Lord, Michael Simpson, Ania B. Koziell, Gavin I. Welsh, and Moin A. Saleem: Genomic and clinical profiling of a national Nephrotic Syndrome cohort advocates a precision medicine approach to disease management. Kidney International 2016, in press.