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Abstract: FR-PO309

Allele-Specific Expression in the Human Kidney: An Analysis of the NEPTUNE Cohort

Session Information

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic


  • Onuchic-Whitford, Ana C., Boston Children's Hospital, Boston, Massachusetts, United States
  • Greenberg, Anya, Boston Children's Hospital, Boston, Massachusetts, United States
  • Mcnulty, Michelle, Boston Children's Hospital, Boston, Massachusetts, United States
  • Han, Seong Kyu, Boston Children's Hospital, Boston, Massachusetts, United States
  • Yoon, Jihoon, Boston Children's Hospital, Boston, Massachusetts, United States
  • Lee, Dongwon, Boston Children's Hospital, Boston, Massachusetts, United States
  • Sampson, Matt G., Boston Children's Hospital, Boston, Massachusetts, United States

Group or Team Name


Allele-specific expression (ASE) is a genomic phenomenon in which one copy of a gene (from one parental chromosome) is expressed more than the other, often due to cis-regulatory genetic variation. ASE has been shown to contribute to autism, heart disease and cancer. However, the extent of ASE in human kidney and its role in the pathogenesis of chronic kidney diseases is not well defined. To address this, we performed ASE analysis using whole genome sequencing data paired with kidney biopsy-derived glomerular RNA-seq data from 240 individuals in the Nephrotic Syndrome Study Network (NEPTUNE).


By integrating genomic and transcriptomic data from the same individual, we quantified mRNA expression originating from either of their parental chromosomes, distinguished by heterozygous loci. To do this, cohort-level genotype data was imputed and population-phased using the Michigan Imputation Server. For each participant, gene-level ASE data for chromosome 19 (chr19) was generated by phASER (phasing and Allele Specific Expression from RNA-seq), and subsequently combined to generate cohort-level ASE data.


1653 genes on chr19 had sufficient glomerular expression for ASE analysis. Of these, 880 genes (53%) had ASE in ≥1 individual. We then focused on the cohort prevalence of ASE for 947 “highly expressed” genes, defined as read count > 100 in ≥1 individual. The median number of highly expressed glomerular genes with ASE per person was 79. NPHS1 – encoding nephrin, a crucial component of the glomerular slit diaphragm – was the 4th most common. Moreover, many of the individuals were outliers for NPHS1 ASE: 13 participants had >5x higher expression of one NPHS1 allele compared to the other. Kallikrein related peptidase 6 (KLK6), the 3rd most common chr19 ASE gene, is expressed in kidney cancers and degrades the glomerular basement membrane proteins collagen and laminin.


This preliminary study of chr19 demonstrates that ASE is a pervasive phenomenon in glomerular cells, occurs in genes implicated in kidney disorders, and is found extensively across patients. This provides strong rationale to extend this ASE study genome-wide, to determine the spectrum of kidney ASE genes, the genetic variants that drive it, and their potential contribution to kidney diseases and traits.


  • NIDDK Support