Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links Tmem63c to kidney damage

Unraveling the genetic susceptibility of complex diseases such as chronic kidney disease remains challenging. Here, we used inbred rat models of kidney damage associated with elevated blood pressure for the comprehensive analysis of a major albuminuria susceptibility locus detected in these models. We characterized its genomic architecture by congenic substitution mapping, targeted next generation sequencing, and compartment-specific RNA sequencing analysis in isolated glomeruli. This led to prioritization of transmembrane proteinTmem63cas a novel potential target.Tmem63c is differentially expressed in glomeruli of allele-specific rat models during onset of albuminuria. Patients with focal segmental glomerulosclerosis exhibited specific TMEM63C loss in podocytes. Functional analysis in zebrafish revealed a role fortmem63cin mediating the glomerular filtration barrier function. Our data demonstrate that integrative analysis of the genomic architecture of a complex trait locus is a powerful tool for identification of new targets such asTmem63c for further translational investigation.
Source: eLife - Category: Biomedical Science Tags: Genetics and Genomics Source Type: research

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Source: Frontiers in Physiology - Category: Physiology Source Type: research
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Source: Veterinary Microbiology - Category: Veterinary Research Source Type: research
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Source: Revista Espanola de Cirugia Ortopedica y Traumatologia - Category: Orthopaedics Source Type: research
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Source: BMC Nephrology - Category: Urology & Nephrology Authors: Tags: Research article Source Type: research
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Source: Nephron - Category: Urology & Nephrology Source Type: research
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Source: Advances in Chronic Kidney Disease - Category: Urology & Nephrology Source Type: research
More News: Biomedical Science | Chronic Kidney Disease | Genetics | Glomeruli | Urology & Nephrology