Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Historical Approach to Genetic Testing in Monogenic Kidney Diseases

Video Transcription

Video Summary

Lisa Gay Woodford (CHOP) reviews the evolution and current use of genetics in clinical nephrology. She traces key milestones from Mendel to Sanger sequencing, the Human Genome Project, and modern population resources such as gnomAD and the NIH All of Us project, emphasizing how improved sequencing and bioinformatics moved genomics into routine diagnosis. She explains the disease-variant landscape (rare, high-effect Mendelian variants vs common, low-effect variants) and notes that >600 genes are linked to monogenic kidney disease, accounting for ~30% of pediatric CKD and ~10% in adults. Woodford outlines testing options—karyotype, microarray, targeted single-gene tests, gene panels, exome, and genome—highlighting tradeoffs like incidental findings and incomplete sensitivity. She gives examples where genetic diagnoses guide therapy (e.g., SRNS, aHUS, XLH, primary hyperoxaluria). Key challenges include access, counseling infrastructure, and variant interpretation (VUS). She highlights emerging long-read/third-generation sequencing and optical mapping to detect complex structural variants.

Asset Subtitle

Lisa M. Guay-Woodford

Keywords

clinical nephrology genomics

monogenic kidney disease genes

genetic testing options exome genome panels

variant interpretation VUS counseling

population genomics resources gnomAD All of Us

long-read sequencing structural variants optical mapping