The landscape of allele-specific expression in human kidneys

Allele-specific expression (ASE), the preferential expression of one gene copy, is a key mechanism of genomic regulation. However, its role in human kidney disease remains poorly understood. In this study, we generated a high-quality, genome-wide ASE map using paired whole-genome sequencing and RNA-seq from microdissected glomerular (GLOM) and tubulointerstitial (TUBE) compartments of patients with proteinuric kidney disease. We showed that the majority of common ASE events were deterministic and sequence-mediated. We also found that diseased kidneys exhibited significantly more ASE in GLOM than TUBE, compared to controls. Unexpectedly, higher ASE in GLOM than TUBE was significantly associated with improved kidney disease outcomes in the disease cohort. Differential gene expression analysis suggested this was the result of an active, protective transcriptional response, including ribosome and ATP synthesis upregulation, rather than pathogenic dysregulation. Our work reveals glomerular ASE as a marker of adaptive transcriptional activity in proteinuric kidney disease.

Authors

Institutions

Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2025-12-09
DOI
https://doi.org/10.64898/2025.12.03.692205
Primary Topic
Renal Diseases and Glomerulopathies
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

The landscape of allele-specific expression in human kidneys

Christopher Lund O'Connor, Anya Greenberg, Eric D. Sakkas, Markus Bitzer et al.
bioRxiv (Cold Spring Harbor Laboratory)
Renal Diseases and Glomerulopathies
article

The landscape of allele-specific expression in human kidneys

Christopher Lund O'Connor, Anya Greenberg, Eric D. Sakkas, Markus Bitzer, Joseph J.�Y. Sung, Matthew Gordon Sampson, Jihoon G. Yoon, Michelle T. McNulty, Ana C. Onuchic-Whitford, Dongwon Lee, Laura Mariani, Sowmya Badina
article en

Abstract

Allele-specific expression (ASE), the preferential expression of one gene copy, is a key mechanism of genomic regulation. However, its role in human kidney disease remains poorly understood. In this study, we generated a high-quality, genome-wide ASE map using paired whole-genome sequencing and RNA-seq from microdissected glomerular (GLOM) and tubulointerstitial (TUBE) compartments of patients with proteinuric kidney disease. We showed that the majority of common ASE events were deterministic and sequence-mediated. We also found that diseased kidneys exhibited significantly more ASE in GLOM than TUBE, compared to controls. Unexpectedly, higher ASE in GLOM than TUBE was significantly associated with improved kidney disease outcomes in the disease cohort. Differential gene expression analysis suggested this was the result of an active, protective transcriptional response, including ribosome and ATP synthesis upregulation, rather than pathogenic dysregulation. Our work reveals glomerular ASE as a marker of adaptive transcriptional activity in proteinuric kidney disease.

bioRxiv (Cold Spring Harbor Laboratory)
Broad Institute (US), Brigham and Women's Hospital (US), Boston Children's Hospital (US), Harvard University (US), Yonsei University (KR), University of Michigan (US), Severance Hospital (KR), Precision for Medicine (United States) (US), Gangnam Severance Hospital (KR), Boston Children's Museum (US), Apollos University (US)
Openalex Percentile: Top 51%
Renal Diseases and Glomerulopathies
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.