ArticleEuropean journal of human genetics : EJHG2016
Whole-genome sequencing overcomes pseudogene homology to diagnose autosomal dominant polycystic kidney disease.
Article in European journal of human genetics : EJHG, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 87 citations in OpenAlex.
- From Guidelines to Practice: Pilot Implementation and Analytical Boundaries of a Focused ADPKD-Spectrum Gene Panel.Diagnostics (Basel, Switzerland) · 2026Article
- A portable recalibration workflow for reference-based variant calling in non-human genomes.PLoS computational biology · 2026Article
- Molecular genetic diagnosis of autosomal dominant polycystic kidney disease - A systematic review.Global medical genetics · 2026Review
- Designing genome editing experiments with EditABLE.Genome biology · 2026Article
- Genetic analysis of autosomal dominant polycystic kidney disease in Iranian families: a combined Sanger and next-generation sequencing study.Journal of applied genetics · 2026Article
- Opportunities for renal genetic evaluation among pregnant patients with kidney disease.Pregnancy (Hoboken, N.J.) · 2026Article
- PKD1 5'UTR variants are a rare cause of disease in ADPKD and suggest a new focus for therapeutic development.European journal of human genetics : EJHG · 2026Article
- Genomic and epigenomic landscape of ADPKD: towards precision diagnostics and tailored treatments.Frontiers in epigenetics and epigenomics · 2026Review
- Genome and transcriptome sequencing reveal pathogenic activation of a pseudoexon inGenetics in medicine open · 2026Article
- Genetic testing in autosomal dominant polycystic kidney disease: why it matters in 2025.Clinical kidney journal · 2025Article
- Genetic etiology of inherited kidney diseases in egyptian patients: next generation sequencing identifies six novel variants.Molecular and cellular pediatrics · 2025Article
- Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine.Pain reports · 2025Article
- Navigating Genetic Testing in Nephrology: Options and Decision-Making Strategies.Kidney international reports · 2025Review
- Novel PKD1 Mutation (c.G10086T) Drives High Intracranial Aneurysm Risk in Autosomal Dominant Polycystic Kidney Disease.European journal of neurology · 2025Article
- Somatic mutation in autosomal dominant polycystic kidney disease revealed by deep sequencing human kidney cysts.NPJ genomic medicine · 2024Article
- Quantifying variant contributions in cystic kidney disease using national-scale whole-genome sequencing.The Journal of clinical investigation · 2024Article
- Article
- Genome Sequencing Unveils the Role of Copy Number Variants in Hearing Loss and Identifies Novel Deletions With Founder Effect in the DFNB1 Locus.Human mutation · 2024Article
- Atypical splicing variants in PKD1 explain most undiagnosed typical familial ADPKD.NPJ genomic medicine · 2023Article
- Visual inspection reveals a novel pathogenic mutation inMolecular medicine reports · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder and is due to disease-causing variants in PKD1 or PKD2. Strong genotype-phenotype correlation exists although diagnostic sequencing is not part of routine clinical practice. This is because PKD1 bears 97.7% sequence similarity with six pseudogenes, requiring laborious and error-prone long-range PCR and Sanger sequencing to overcome. We hypothesised that whole-genome sequencing (WGS) would be able to overcome the problem of this sequence homology, because of 150 bp, paired-end reads and avoidance of capture bias that arises from targeted sequencing. We prospectively recruited a cohort of 28 unique pedigrees with ADPKD phenotype. Standard DNA extraction, library preparation and WGS were performed using Illumina HiSeq X and variants were classified following standard guidelines. Molecular diagnosis was made in 24 patients (86%), with 100% variant confirmation by current gold standard of long-range PCR and Sanger sequencing. We demonstrated unique alignment of sequencing reads over the pseudogene-homologous region. In addition to identifying function-affecting single-nucleotide variants and indels, we identified single- and multi-exon deletions affecting PKD1 and PKD2, which would have been challenging to identify using exome sequencing. We report the first use of WGS to diagnose ADPKD. This method overcomes pseudogene homology, provides uniform coverage, detects all variant types in a single test and is less labour-intensive than current techniques. This technique is translatable to a diagnostic setting, allows clinicians to make better-informed management decisions and has implications for other disease groups that are challenged by regions of confounding sequence homology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.