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Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney

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Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney. / Schierbaum, Luca M; Schneider, Sophia; Buerger, Florian; Halawi, Abdul Aziz; Seltzsam, Steve; Wang, Chunyan; Zheng, Bixia; Wu, Chen-Han Wilfried; Dai, Rufeng; Connaughton, Dervla M; Salmanullah, Daanya; Nakayama, Makiko; Mann, Nina; Shril, Shirlee; Hildebrandt, Friedhelm.

In: NEPHRON, Vol. 147, No. 11, 2023, p. 685-692.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schierbaum, LM, Schneider, S, Buerger, F, Halawi, AA, Seltzsam, S, Wang, C, Zheng, B, Wu, C-HW, Dai, R, Connaughton, DM, Salmanullah, D, Nakayama, M, Mann, N, Shril, S & Hildebrandt, F 2023, 'Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney', NEPHRON, vol. 147, no. 11, pp. 685-692. https://doi.org/10.1159/000531770

APA

Schierbaum, L. M., Schneider, S., Buerger, F., Halawi, A. A., Seltzsam, S., Wang, C., Zheng, B., Wu, C-H. W., Dai, R., Connaughton, D. M., Salmanullah, D., Nakayama, M., Mann, N., Shril, S., & Hildebrandt, F. (2023). Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney. NEPHRON, 147(11), 685-692. https://doi.org/10.1159/000531770

Vancouver

Schierbaum LM, Schneider S, Buerger F, Halawi AA, Seltzsam S, Wang C et al. Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney. NEPHRON. 2023;147(11):685-692. https://doi.org/10.1159/000531770

Bibtex

@article{1cd5609039ab4983aece718ff9a62491,
title = "Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney",
abstract = "INTRODUCTION: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first 3 decades of life. Over 40 genes have been identified as causative for isolated human CAKUT. However, many genes remain unknown, and the prioritization of potential CAKUT candidate genes is challenging. To develop an independent approach to prioritize CAKUT candidate genes, we hypothesized that monogenic CAKUT genes are most likely co-expressed along a temporal axis during kidney development and that genes with coinciding high expression may represent strong novel CAKUT candidate genes.METHODS: We analyzed single-cell mRNA (sc-mRNA) transcriptomics data of human fetal kidney for temporal sc-mRNA co-expression of 40 known CAKUT genes. A maximum of high expression in consecutive timepoints of kidney development was found for four of the 40 genes (EYA1, SIX1, SIX2, and ITGA8) in nephron progenitor cells a, b, c, d (NPCa-d). We concluded that NPCa-d are relevant for CAKUT pathogenesis and intersected two lists of CAKUT candidate genes resulting from unbiased whole-exome sequencing (WES) with the 100 highest expressed genes in NPCa-d.RESULTS: Intersection of the 100 highest expressed genes in NPCa-d with WES-derived CAKUT candidate genes identified an overlap with the candidate genes KIF19, TRIM36, USP35, CHTF18, in each of which a biallelic variant was detected in different families with CAKUT.CONCLUSION: Sc-mRNA expression data of human fetal kidney can be utilized to prioritize WES-derived CAKUT candidate genes. KIF19, TRIM36, USP35, and CHTF18 may represent strong novel candidate genes for CAKUT.",
keywords = "Humans, Transcriptome, Kidney/abnormalities, Urinary Tract/abnormalities, RNA, Messenger, Homeodomain Proteins, Endopeptidases",
author = "Schierbaum, {Luca M} and Sophia Schneider and Florian Buerger and Halawi, {Abdul Aziz} and Steve Seltzsam and Chunyan Wang and Bixia Zheng and Wu, {Chen-Han Wilfried} and Rufeng Dai and Connaughton, {Dervla M} and Daanya Salmanullah and Makiko Nakayama and Nina Mann and Shirlee Shril and Friedhelm Hildebrandt",
note = "{\textcopyright} 2023 S. Karger AG, Basel.",
year = "2023",
doi = "10.1159/000531770",
language = "English",
volume = "147",
pages = "685--692",
journal = "NEPHRON",
issn = "1660-8151",
publisher = "S. Karger AG",
number = "11",

}

RIS

TY - JOUR

T1 - Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney

AU - Schierbaum, Luca M

AU - Schneider, Sophia

AU - Buerger, Florian

AU - Halawi, Abdul Aziz

AU - Seltzsam, Steve

AU - Wang, Chunyan

AU - Zheng, Bixia

AU - Wu, Chen-Han Wilfried

AU - Dai, Rufeng

AU - Connaughton, Dervla M

AU - Salmanullah, Daanya

AU - Nakayama, Makiko

AU - Mann, Nina

AU - Shril, Shirlee

AU - Hildebrandt, Friedhelm

N1 - © 2023 S. Karger AG, Basel.

PY - 2023

Y1 - 2023

N2 - INTRODUCTION: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first 3 decades of life. Over 40 genes have been identified as causative for isolated human CAKUT. However, many genes remain unknown, and the prioritization of potential CAKUT candidate genes is challenging. To develop an independent approach to prioritize CAKUT candidate genes, we hypothesized that monogenic CAKUT genes are most likely co-expressed along a temporal axis during kidney development and that genes with coinciding high expression may represent strong novel CAKUT candidate genes.METHODS: We analyzed single-cell mRNA (sc-mRNA) transcriptomics data of human fetal kidney for temporal sc-mRNA co-expression of 40 known CAKUT genes. A maximum of high expression in consecutive timepoints of kidney development was found for four of the 40 genes (EYA1, SIX1, SIX2, and ITGA8) in nephron progenitor cells a, b, c, d (NPCa-d). We concluded that NPCa-d are relevant for CAKUT pathogenesis and intersected two lists of CAKUT candidate genes resulting from unbiased whole-exome sequencing (WES) with the 100 highest expressed genes in NPCa-d.RESULTS: Intersection of the 100 highest expressed genes in NPCa-d with WES-derived CAKUT candidate genes identified an overlap with the candidate genes KIF19, TRIM36, USP35, CHTF18, in each of which a biallelic variant was detected in different families with CAKUT.CONCLUSION: Sc-mRNA expression data of human fetal kidney can be utilized to prioritize WES-derived CAKUT candidate genes. KIF19, TRIM36, USP35, and CHTF18 may represent strong novel candidate genes for CAKUT.

AB - INTRODUCTION: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first 3 decades of life. Over 40 genes have been identified as causative for isolated human CAKUT. However, many genes remain unknown, and the prioritization of potential CAKUT candidate genes is challenging. To develop an independent approach to prioritize CAKUT candidate genes, we hypothesized that monogenic CAKUT genes are most likely co-expressed along a temporal axis during kidney development and that genes with coinciding high expression may represent strong novel CAKUT candidate genes.METHODS: We analyzed single-cell mRNA (sc-mRNA) transcriptomics data of human fetal kidney for temporal sc-mRNA co-expression of 40 known CAKUT genes. A maximum of high expression in consecutive timepoints of kidney development was found for four of the 40 genes (EYA1, SIX1, SIX2, and ITGA8) in nephron progenitor cells a, b, c, d (NPCa-d). We concluded that NPCa-d are relevant for CAKUT pathogenesis and intersected two lists of CAKUT candidate genes resulting from unbiased whole-exome sequencing (WES) with the 100 highest expressed genes in NPCa-d.RESULTS: Intersection of the 100 highest expressed genes in NPCa-d with WES-derived CAKUT candidate genes identified an overlap with the candidate genes KIF19, TRIM36, USP35, CHTF18, in each of which a biallelic variant was detected in different families with CAKUT.CONCLUSION: Sc-mRNA expression data of human fetal kidney can be utilized to prioritize WES-derived CAKUT candidate genes. KIF19, TRIM36, USP35, and CHTF18 may represent strong novel candidate genes for CAKUT.

KW - Humans

KW - Transcriptome

KW - Kidney/abnormalities

KW - Urinary Tract/abnormalities

KW - RNA, Messenger

KW - Homeodomain Proteins

KW - Endopeptidases

U2 - 10.1159/000531770

DO - 10.1159/000531770

M3 - SCORING: Journal article

C2 - 37499630

VL - 147

SP - 685

EP - 692

JO - NEPHRON

JF - NEPHRON

SN - 1660-8151

IS - 11

ER -