top of page

Long-Read Sequencing

Comprehensive Analysis of PKD1 and PKD2 (CAPKD)

Improves the ADPKD Resolution with High-Fidelity Read

Standard Genetic Testing Fails in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) genetic testing is required when imaging and family history cannot provide a diagnosis, particularly in young patients. While PKD1 and PKD2 variants account for the majority of ADPKD cases, standard methods struggle to resolve the full spectrum of PKD1 variants.

​

NGS often fails towards PKD1 gene, particularly in capture-based assays. This is due to high sequence similarity with six pseudogenes and GC-rich regions. Consequently, WES sensitivity for PKD1 may be as low as 50%¹, and even non-capture WGS struggles with poor alignment with short-read length², leaving some cases without a definitive diagnosis.

Improves PKD1 Mapping with LRS

Leveraging SMRT technology, Comprehensive Analysis of PKD1 and PKD2 (CAPKD) overcomes the "dark regions" of the genome. By generating long reads, we can distinguish the functional PKD1 gene from its pseudogenes with superior accuracy, ensuring reliable variant detection where short-read NGS fails.

Clinical Performance: Outperforming Conventional Testing

vs. Capture-Based NGS³

  • Increased detection yield by solving 31% of cases that genetically unexplained

A total of 40 clinically diagnosed ADPKD patients without full genetic characterization by NGS were retrospectively enrolled³

vs. Combined Strategy (LR-PCR NGS + MLPA)⁴

  • Identified variants in 16% of ADPKD patients that previously returned negative findings 

  • Corrected 33% of large deletions where MLPA produced discrepancy

In a retrospective study of 170 unrelated ADPKD patients⁴

Send-out Testing

When considering our send-out sequencing services:

  1. Consultation: Contact our team for the most current test specifications.

  2. Sample Preparation: Check sample types and shipment requirements to ensure high-quality results. Please check your local export regulations and logistics partners.

  3. Submission: Contact Xcelom when placing an order. Include the completed Test Request and Consent Form, along with any required documents.

Sample Requirements

Peripheral Blood: 2 mL in EDTA tube

Dried Blood Spot (DBS): 3 spots, ≥ 8mm diameter each

Long-fragment gDNA

Transport Conditions

2-8℃, arrive within 72 hours

Testing Scope

Detects ADPKD-associated variants in the PKD1 and PKD2 genes, including:

  • Pathogenic (P), Likely Pathogenic(LP), and some VUS SNVs/InDels

  • Exon deletions/duplications

Turnaround Time (TAT)

17 working days

End-to-End Technology Transfer

Berry Genomics and Xcelom provide dedicated end-to-end workflow to bring this capability into your laboratory. We offer end-to-end support, including:

  • Lab Setup: Consultation on workflow, equipment, and customized kits.

  • Training: Comprehensive wet-lab training for your staff.

  • Bioinformatics Support: Our tailored software solutions streamline variant annotation and interpretation, automatically integrating public databases to assist with ACMG analysis.

Resources

References:

1. Ali H, Al-Mulla F, Hussain N, et al. PKD1 Duplicated regions limit clinical Utility of Whole Exome Sequencing for Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease. Sci Rep. 2019;9(1):4141.

2. Borràs DM, Vossen RHAM, Liem M, et al. Detecting PKD1 variants in polycystic kidney disease patients by single-molecule long-read sequencing. Hum Mutat. 2017;38(7):870-879.

3. Sun Q, Xu P, Mao A, et al. Targeted long-read sequencing enables higher diagnostic yield of ADPKD by accurate PKD1 genetic analysis. NPJ Genom Med. 2025;10(1):22. 

4. Xu D, Mao A, Chen L, Wu L, Ma Y, Mei C. Comprehensive Analysis of PKD1 and PKD2 by Long-Read Sequencing in Autosomal Dominant Polycystic Kidney Disease. Clin Chem. 2024;70(6):841-854.

bottom of page