Identification of Gene Mutations in Autosomal Dominant Polycystic Kidney Disease through Targeted Resequencing
Sandro Rossetti,Katharina Hopp,Robert A. Sikkink,Jamie L. Sundsbak,Yean Kit Lee,Vickie J. Kubly,Bruce W. Eckloff,Christopher J. Ward,Christopher G. Winearls,Vicente E. Torres,Peter C. Harris +10 more
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TLDR
A strategy to analyze both the PKD1 and PKD2 genes using next-generation sequencing by pooling long-range PCR amplicons and multiplexing bar-coded libraries is developed and validated and is a model for future genetic characterization of large ADPKD populations.Abstract:
Mutations in two large multi-exon genes, PKD1 and PKD2, cause autosomal dominant polycystic kidney disease (ADPKD). The duplication of PKD1 exons 1-32 as six pseudogenes on chromosome 16, the high level of allelic heterogeneity, and the cost of Sanger sequencing complicate mutation analysis, which can aid diagnostics of ADPKD. We developed and validated a strategy to analyze both the PKD1 and PKD2 genes using next-generation sequencing by pooling long-range PCR amplicons and multiplexing bar-coded libraries. We used this approach to characterize a cohort of 230 patients with ADPKD. This process detected definitely and likely pathogenic variants in 115 (63%) of 183 patients with typical ADPKD. In addition, we identified atypical mutations, a gene conversion, and one missed mutation resulting from allele dropout, and we characterized the pattern of deep intronic variation for both genes. In summary, this strategy involving next-generation sequencing is a model for future genetic characterization of large ADPKD populations.read more
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Journal ArticleDOI
Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Arlene B. Chapman,Olivier Devuyst,Kai-Uwe Eckardt,Ron T. Gansevoort,Tess Harris,Shigeo Horie,Bertram L. Kasiske,Dwight Odland,York Pei,Ronald D. Perrone,Yves Pirson,Robert W. Schrier,Roser Torra,Vicente E. Torres,Terry Watnick,David C. Wheeler +15 more
TL;DR: This review summarized areas of consensus, gaps in knowledge, and research and health-care priorities related to diagnosis; monitoring of kidney disease progression; management of hypertension, renal function decline and complications; end-stage renal disease; extrarenal complications; and practical integrated patient support that are summarized in this review.
Journal ArticleDOI
Type of PKD1 mutation influences renal outcome in ADPKD.
Emilie Cornec-Le Gall,Marie-Pierre Audrézet,Marie-Pierre Audrézet,Jian-Min Chen,Jian-Min Chen,Maryvonne Hourmant,M.P. Morin,Régine Perrichot,Christophe Charasse,Bassem Whebe,E. Renaudineau,P. Jousset,Marie-Paule Guillodo,Anne Grall-Jezequel,Philippe Saliou,Philippe Saliou,Claude Férec,Claude Férec,Yannick Le Meur +18 more
TL;DR: It is confirmed that renal survival associated with PKD2 mutations was approximately 20 years longer than that associated withPKD1 mutations, and the type of PKD1 mutation, but not its position, correlated strongly with renal survival.
Journal ArticleDOI
Polycystic kidney disease.
Carsten Bergmann,Lisa M. Guay-Woodford,Peter C. Harris,Shigeo Horie,Dorien J.M. Peters,Vicente E. Torres +5 more
TL;DR: An overview of the current knowledge of PKD and its treatment can be found in this paper, where the authors provide an overview of existing knowledge about the pathogenesis and treatment of polycystic kidney disease.
Journal ArticleDOI
Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease.
TL;DR: An improved understanding of aberrant downstream pathways in ADPKD, such as proliferation/secretion-related signaling, energy metabolism, and activated macrophages, in which cAMP and calcium changes may play a role, is leading to the identification of therapeutic targets.
Journal ArticleDOI
Improved genetic testing for monogenic diabetes using targeted next-generation sequencing
Sian Ellard,H Lango Allen,E. De Franco,Sarah E. Flanagan,Gerald Hysenaj,Kevin Colclough,Jayne A L Houghton,Maggie Shepherd,Andrew T. Hattersley,Michael N. Weedon,Richard Caswell +10 more
TL;DR: A novel targeted next-generation sequencing assay provides a highly sensitive method for simultaneous analysis of all monogenic diabetes genes and can detect mutations previously identified by Sanger sequencing or multiplex ligation-dependent probe amplification dosage analysis.
References
More filters
Journal ArticleDOI
Sequencing technologies-the next generation
TL;DR: A technical review of template preparation, sequencing and imaging, genome alignment and assembly approaches, and recent advances in current and near-term commercially available NGS instruments is presented.
Journal ArticleDOI
Alternative Isoform Regulation in Human Tissue Transcriptomes
Eric T. Wang,Rickard Sandberg,Rickard Sandberg,Shujun Luo,Irina Khrebtukova,Lu Zhang,Christine Mayr,Stephen F. Kingsmore,Gary P. Schroth,Christopher B. Burge +9 more
TL;DR: An in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments yielding a digital inventory of gene and mRNA isoform expression suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.
Journal ArticleDOI
Next-Generation DNA Sequencing Methods
TL;DR: An astounding potential exists for next-generation DNA sequencing technologies to bring enormous change in genetic and biological research and to enhance the authors' fundamental biological knowledge.
Journal ArticleDOI
Human Splicing Finder: an online bioinformatics tool to predict splicing signals
François Olivier Desmet,Dalil Hamroun,Marine Lalande,Gwenaëlle Collod-Béroud,Mireille Claustres,Christophe Béroud +5 more
TL;DR: Human Splicing Finder is designed, a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence, and it is shown that the mutation effect was correctly predicted in almost all cases.
Journal ArticleDOI
Exome sequencing identifies the cause of a Mendelian disorder
Sarah B H Ng,Kati J. Buckingham,Choli Lee,Abigail W. Bigham,Holly K. Tabor,Holly K. Tabor,Karin M. Dent,Chad D. Huff,Paul Shannon,Ethylin Wang Jabs,Ethylin Wang Jabs,Deborah A. Nickerson,Jay Shendure,Michael J. Bamshad,Michael J. Bamshad +14 more
TL;DR: Exome sequencing of a small number of unrelated affected individuals is a powerful, efficient strategy for identifying the genes underlying rare mendelian disorders and will likely transform the genetic analysis of monogenic traits.
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