O21: A rapid, novel approach to rare disease and clinical genetic variant discovery using on-flowcell proximity sequencing and haplotype-resolved variant calling

Genetics in Medicine Open 2026 Open access

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Authors: Shunhua Han, Vitor Onuchic, Varun Jain, Arun Karthi Subramaniyan, Žarko Tasev, Stephen G. Gaffney, Fabian Klötzl, Drew Ellershaw, Sean Humphray, Ali Crawford, Mitch Bekritsky, Jacqui Weir
+27 more James Han, Joseph M. Devaney, Aaron Johnson, Flavia M. Facio, Keith Nykamp, Julianna Spangler, Leah H. Matzat, Dalia M. Dhingra, Ashley Sirard, Joy Hwang, Nathan Usem, Arun Ramani, Nirav Malani, Deborah Boles, Robert D. Daber, Katie L. Larkin, Yueyao Gao, Michelle C. Cipicchio, Mark Fleharty, Victoria Popic, Sean E. Hofherr, Marina T. DiStefano, Diana M. Toledo, Niall J. Lennon, Inga Nagel, Inga Vater, Malte Spielmann
DOI: 10.1016/j.gimo.2026.104308
Cited by: 0

Abstract

Despite the widespread adoption of genomics, rare-disease testing remains unevenly accessible and is often a prolonged diagnostic odyssey for months or years due to stepwise testing. This challenge is magnified for medically relevant paralogous loci, where high homology and structural complexity create difficulty for standard short-read sequencing. Current clinical workflows often require targeted orthogonal assays (eg, MLPA, LR-PCR) that rarely provide haplotype resolution at large distances, or long-read reflex testing, adding cost and days of turnaround.

Fields of Study & Subjects

Genomics and Rare Diseases Genomics and Phylogenetic Studies Genomic variations and chromosomal abnormalities

Publication details

Journal / source
Genetics in Medicine Open
Volume
4
Pages
104308–104308
Publication date
1 January 2026
Language
EN