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, Jahrgang 147, Nr. 11, 2023, S. 685-692.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -