A protocol for the identification and validation of novel genetic causes of kidney disease

BMC Nephrology

Melissa Little⁹  Helen Healy³  Cas Simons¹  Ryan Taft¹  Ernst Wolvetang²  Wendy E. Hoy³  Valentine Hyland^1,12  Hugh J. McCarthy^1,10  Cathy Quinlan⁵  George John^1,13  Georgina Caruana⁷  Michel C. Tchan⁴  Gopala Rangan⁸  Stephen I. Alexander^1,10  Peter Trnka^1,14  Anne Cameron³  Minoru Takasato⁹  Michael Gabbett⁶  Julie McGaughran^1,11  Barbara Maier⁹  Chirag Patel^1,11  Andrew Mallett¹ 

[1] Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia;Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Australia;Centre for Kidney Disease Research, Centre for Chronic Disease and CKD.QLD, School of Medicine, The University of Queensland, St Lucia, Australia;Department of Genetic Medicine, Westmead Hospital, Sydney and Sydney Medical School, The University of Sydney, Sydney, Australia;Department of Nephrology, Royal Children’s Hospital, Melbourne, Australia;School of Medicine, Griffith University, Brisbane, Australia;Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia;Department of Nephrology, Westmead Hospital, Sydney and Sydney Medical School, The University of Sydney, Sydney, Australia;Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Australia;Department of Nephrology, Children’s Hospital at Westmead, Sydney and Sydney Medical School, The University of Sydney, Sydney, Australia;Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia;Molecular Genetics Laboratory, Pathology Queensland and Royal Brisbane and Women’s Hospital, Brisbane, Australia;Kidney Health Service and Conjoint Kidney Research Laboratory, Royal Brisbane and Women’s Hospital, Brisbane, Australia;Queensland Child and Adolescent Renal Service, Lady Cilento Children’s Hospital, Brisbane, Australia

关键词: Induced pluripotent stem cell;    Genetic sequencing;    Nephrogenetics;    Nephrology;    Chronic kidney disease;   

Others  :  1225238
DOI  :  10.1186/s12882-015-0148-8

 received in 2015-07-09, accepted in 2015-09-07,  发布年份 2015

【 摘 要 】

Background

Genetic renal diseases (GRD) are a heterogeneous and incompletely understood group of disorders accounting for approximately 10 % of those diagnosed with kidney disease. The advent of Next Generation sequencing and new approaches to disease modelling may allow the identification and validation of novel genetic variants in patients with previously incompletely explained or understood GRD.

Methods/Design

This study will recruit participants in families/trios from a multidisciplinary sub-specialty Renal Genetics Clinic where known genetic causes of GRD have been excluded or where genetic testing is not available. After informed patient consent, whole exome and/or genome sequencing will be performed with bioinformatics analysis undertaken using a customised variant assessment tool. A rigorous process for participant data management will be undertaken. Novel genetic findings will be validated using patient-derived induced pluripotent stem cells via differentiation to renal and relevant extra-renal tissue phenotypes in vitro. A process for managing the risk of incidental findings and the return of study results to participants has been developed.

Discussion

This investigator-initiated approach brings together experts in nephrology, clinical and molecular genetics, pathology and developmental biology to discover and validate novel genetic causes for patients in Australia affected by GRD without a known genetic aetiology or pathobiology.

【 授权许可】

   
2015 Mallett et al.

【 图 表 】

Fig. 1.

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