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

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 vali...

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Autores principales: Mallett, Andrew, Patel, Chirag, Maier, Barbara, McGaughran, Julie, Gabbett, Michael, Takasato, Minoru, Cameron, Anne, Trnka, Peter, I. Alexander, Stephen, Rangan, Gopala, Tchan, Michel C., Caruana, Georgina, John, George, Quinlan, Cathy, McCarthy, Hugh J., Hyland, Valentine, E. Hoy, Wendy, Wolvetang, Ernst, Taft, Ryan, Simons, Cas, Healy, Helen, Little, Melissa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570515/
https://www.ncbi.nlm.nih.gov/pubmed/26374634
http://dx.doi.org/10.1186/s12882-015-0148-8
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author Mallett, Andrew
Patel, Chirag
Maier, Barbara
McGaughran, Julie
Gabbett, Michael
Takasato, Minoru
Cameron, Anne
Trnka, Peter
I. Alexander, Stephen
Rangan, Gopala
Tchan, Michel C.
Caruana, Georgina
John, George
Quinlan, Cathy
McCarthy, Hugh J.
Hyland, Valentine
E. Hoy, Wendy
Wolvetang, Ernst
Taft, Ryan
Simons, Cas
Healy, Helen
Little, Melissa
author_facet Mallett, Andrew
Patel, Chirag
Maier, Barbara
McGaughran, Julie
Gabbett, Michael
Takasato, Minoru
Cameron, Anne
Trnka, Peter
I. Alexander, Stephen
Rangan, Gopala
Tchan, Michel C.
Caruana, Georgina
John, George
Quinlan, Cathy
McCarthy, Hugh J.
Hyland, Valentine
E. Hoy, Wendy
Wolvetang, Ernst
Taft, Ryan
Simons, Cas
Healy, Helen
Little, Melissa
author_sort Mallett, Andrew
collection PubMed
description 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.
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spelling pubmed-45705152015-09-16 A protocol for the identification and validation of novel genetic causes of kidney disease Mallett, Andrew Patel, Chirag Maier, Barbara McGaughran, Julie Gabbett, Michael Takasato, Minoru Cameron, Anne Trnka, Peter I. Alexander, Stephen Rangan, Gopala Tchan, Michel C. Caruana, Georgina John, George Quinlan, Cathy McCarthy, Hugh J. Hyland, Valentine E. Hoy, Wendy Wolvetang, Ernst Taft, Ryan Simons, Cas Healy, Helen Little, Melissa BMC Nephrol Study Protocol 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. BioMed Central 2015-09-15 /pmc/articles/PMC4570515/ /pubmed/26374634 http://dx.doi.org/10.1186/s12882-015-0148-8 Text en © Mallett et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Mallett, Andrew
Patel, Chirag
Maier, Barbara
McGaughran, Julie
Gabbett, Michael
Takasato, Minoru
Cameron, Anne
Trnka, Peter
I. Alexander, Stephen
Rangan, Gopala
Tchan, Michel C.
Caruana, Georgina
John, George
Quinlan, Cathy
McCarthy, Hugh J.
Hyland, Valentine
E. Hoy, Wendy
Wolvetang, Ernst
Taft, Ryan
Simons, Cas
Healy, Helen
Little, Melissa
A protocol for the identification and validation of novel genetic causes of kidney disease
title A protocol for the identification and validation of novel genetic causes of kidney disease
title_full A protocol for the identification and validation of novel genetic causes of kidney disease
title_fullStr A protocol for the identification and validation of novel genetic causes of kidney disease
title_full_unstemmed A protocol for the identification and validation of novel genetic causes of kidney disease
title_short A protocol for the identification and validation of novel genetic causes of kidney disease
title_sort protocol for the identification and validation of novel genetic causes of kidney disease
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570515/
https://www.ncbi.nlm.nih.gov/pubmed/26374634
http://dx.doi.org/10.1186/s12882-015-0148-8
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