Abstract: TH-PO0634
Identification of Novel Kidney-Specific Human Imprinted Genes Through Allele-Specific Expression Analysis
Session Information
- Genetic Diseases of the Kidneys: Complex Kidney Traits
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits
Authors
- Sakkas, Erotokritos, Boston Children's Hospital, Boston, Massachusetts, United States
- Onuchic-Whitford, Ana C., Brigham and Women's Hospital, Boston, Massachusetts, United States
- Sung, Junmo, Brigham and Women's Hospital, Boston, Massachusetts, United States
- McNulty, Michelle, Boston Children's Hospital, Boston, Massachusetts, United States
- Greenberg, Anya, Boston Children's Hospital, Boston, Massachusetts, United States
- Yoon, Jihoon, Yonsei University College of Medicine, Seodaemun-gu, Korea (the Republic of)
- Badina, Sowmya, The Apollo University, Chittoor, AP, India
- Sampson, Matt G., Boston Children's Hospital, Boston, Massachusetts, United States
- Lee, Dongwon, Boston Children's Hospital, Boston, Massachusetts, United States
Group or Team Name
- Nephrotic Syndrome Study Network (NEPTUNE).
Background
Genomic imprinting is a major mechanism of monoallelic expression. It describes a phenomenon where a gene is silenced during gametogenesis, leading to expression of only one parent’s allele in the diploid organism. Because of the parent-of-origin effect, imprinting has a distinct characteristic from other allele-specific expression (ASE) mechanisms: monoallelic expression of a gene in all individuals and random selection of the expressed haplotype between individuals. Imprinting is tissue-specific, as tissues can lose imprinting over time. Here, we analyze ASE data from NEPTUNE (Nephrotic Syndrome Study Network) to identify imprinted genes in kidney glomeruli (GLOM) and tubulointerstitium (TUBE) in proteinuric disease.
Methods
We used paired whole-genome sequencing (WGS) and RNA-seq data from 222 GLOM samples and 206 TUBE samples from NEPTUNE participants, using stringent quality control and phASER to create a population-level ASE dataset. Then, we adapted a pipeline by Baran et al (PMID 25953952) that assigns an imprinting likelihood to genes in an ASE dataset—searching for widespread, allele-agnostic monoallelic expression—and we identified imprinted genes in each kidney compartment. We updated the pipeline to avoid identifying genes if better explained by eQTLs. Finally, we curated a list of 299 known imprinted genes across all human tissues through literature review and compared this list to our NEPTUNE imprinted gene list.
Results
We identified 19 imprinted genes in GLOM, 2 not previously identified in any tissue, and 15 imprinted genes in TUBE, including 2 novel. The genes exhibiting ASE in the largest number of samples, such as SNHG14 and ZNF331, were explained by genomic imprinting. Notably, 10 genes initially identified as imprinted were found to have expression patterns highly consistent with eQTL effect, and were removed. 97.3% of known imprinted genes were not found as imprinted in either NEPTUNE tissue.
Conclusion
By combining quality-controlled ASE data with a rigorous imprinting-identification pipeline, we identified imprinted genes unique to the GLOM and TUBE. Some genes had not been previously identified—10.5% in GLOM and 13.3% in TUBE—highlighting the tissue-specificity of imprinting and the importance of generating a high-quality ASE dataset.
Funding
- NIDDK Support