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Peer-reviewedCC BY-NCScience Advances

The landscape of allele-specific expression in human kidneys

  • Ana C. Onuchic-Whitford1,2,3,4
  • Junmo Sung1,2,3,4
  • Eric D. Sakkas2,3,4
  • Michelle T. McNulty2,3,4
  • Victoria Mezger2,3,4,5
  • Christopher L. O’Connor6
  • Anya Greenberg2,3,4
  • Jihoon G. Yoon2,7,8
  • Sowmya Badina2,9
  • Laura H. Mariani6
  • Markus Bitzer6
  • Matthew G. Sampson2,3,4
1 more authors
  • Dongwon Lee2,3,4
9 affiliations
  1. 1Division of Nephrology, Brigham and Women’s Hospital, Boston, MA 02115, USA.
  2. 2Division of Nephrology, Boston Children’s Hospital, Boston, MA 02115, USA.
  3. 3Harvard Medical School, Boston, MA 02115, USA.
  4. 4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  5. 5Medical Faculty, Heidelberg University, Heidelberg 69120, Germany.
  6. 6Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  7. 7Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
  8. 8Department of Laboratory Medicine, Gangnam Severance Hospital, Seoul 06273, Republic of Korea.
  9. 9Centre for Digital Health and Precision Medicine, The Apollo University, Chittoor 517127, India.
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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.

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Cite

BibTeXRIS
BibTeX
@article{onuchicwhitford2026landscape,
  title = {{The landscape of allele-specific expression in human kidneys}},
  author = {Ana C. Onuchic-Whitford and Junmo Sung and Eric D. Sakkas and Michelle T. McNulty and Victoria Mezger and Christopher L. O’Connor and Anya Greenberg and Jihoon G. Yoon and Sowmya Badina and Laura H. Mariani and Markus Bitzer and Matthew G. Sampson and Dongwon Lee},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeg3462},
  url = {https://www.science.org/doi/10.1126/sciadv.aeg3462},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - The landscape of allele-specific expression in human kidneys
AU  - Ana C. Onuchic-Whitford
AU  - Junmo Sung
AU  - Eric D. Sakkas
AU  - Michelle T. McNulty
AU  - Victoria Mezger
AU  - Christopher L. O’Connor
AU  - Anya Greenberg
AU  - Jihoon G. Yoon
AU  - Sowmya Badina
AU  - Laura H. Mariani
AU  - Markus Bitzer
AU  - Matthew G. Sampson
AU  - Dongwon Lee
PY  - 2026
DA  - 2026/10/02
JO  - Science Advances
DO  - 10.1126/sciadv.aeg3462
UR  - https://www.science.org/doi/10.1126/sciadv.aeg3462
AB  - 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.
SN  - 2375-2548
ER  -