Identification of CAKUT-associated genes using a worldwide patient-cohort and high-throughput methods for genetic analysis

点击翻译按钮获取中文摘要

Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT) comprise a large spectrum of pathological conditions. CAKUT contribute to 50% of terminal kidney diseases during the first two decades of life and often necessitate cost-intensive kidney-replacement-therapies in the long term. CAKUT are currently believed to develop predominantly based on abnormalities in the DNA of the affected. However, until today only a small fraction of disease-related genes has successfully been identified and functionally characterized. Dr. Hildebrandt (HHMI, Boston Childrens Hospital, Harvard Medical School) has established a diagnostic approach for the efficient identification of CAKUT-associated genes in his laboratory. Throughout the next few years, the applicant is planning to apply these high-throughput methods for genetic analysis (e.g. homozygosity mapping, whole exome sequencing) to his existing, world-wide cohort of 2,400 families with CAKUT. The applicant will furthermore utilize the methods to analyze the DNA of an own cohort consisting of nearly 150 patients with anorectal malformations and associated CAKUT. In the long term, there is hope that a successful identification of an increasing number of CAKUT-genes can contribute to a better understanding of disease-associated molecular pathways and the pathophysiology of CAKUT overall.