Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Understanding Genetic Testing: Next-Generation Sequencing Panels, Whole-Exome Sequencing, Whole-Genome Sequencing, and Beyond

Understanding Genetic Testing: Next-Generation Sequencing Panels, Whole-Exome Sequencing, Whole-Genome Sequencing, and Beyond

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Video Summary

Dr. Peter Harris reviews why genetic testing is important in kidney disease: monogenic causes are common and involve many genes, so broad testing is often needed. He compares testing approaches. Sanger sequencing is accurate and useful for family segregation, but too slow and expensive for first-line screening. Targeted next-generation sequencing (NGS) panels capture selected kidney-related genes, offering high read depth, lower cost, easier analysis, and better detection of low-level mosaicism, but panels are inflexible when new genes are discovered. Whole-exome sequencing (WES) surveys all coding genes and allows reanalysis as knowledge evolves, but may miss GC-rich or duplicated regions. Whole-genome sequencing (WGS) provides more even coverage and better detection of copy-number variants and noncoding changes, but has higher data burden and may miss mosaicism at typical coverage.<br /><br />Harris highlights challenges in ADPKD, including minor genes, prognostic value of mutation type, and emerging genotype-specific therapies. He presents cases showing misclassification due to population frequency, detection of mosaic PKD2 variants with deep sequencing, and PKD1 pitfalls due to pseudogenes/segmental duplication—sometimes requiring long-range PCR or long-read sequencing (PacBio/Oxford Nanopore) to detect deletions or gene conversion events.<br /><br />Finally, he outlines variant interpretation using population databases (gnomAD), ClinVar, in silico and splicing tools, functional data, segregation, de novo status, and conservative ACMG criteria—often yielding many VUS—emphasizing expert multidisciplinary review and collaboration.

Asset Subtitle

Peter Harris

Meta Tag

Module GENE

Speaker Peter Harris

Keywords

genetic testing

kidney disease

next-generation sequencing

whole-exome sequencing

whole-genome sequencing

ADPKD

variant interpretation