Molecular Genetics and Biomarker Core

MOLECULAR GENETICS AND BIOMARKER CORE SUMMARY/ABSTRACT The Molecular Genetics and Biomarker Core (MGBC) provides services to genetically characterize polycystic kidney disease (PKD) patients, with a focus on autosomal dominant polycystic kidney disease (ADPKD), and to facilitate collection and processing of samples to test biomarkers and to explore the pathophysiology of PKD. The core is directed by Dr. Peter C Harris, an expert in genetic studies of PKD. During the previous funding period the core provided services to ~80 investigators from Mayo and beyond, with a total of >4500 services performed. The MGBC is now enhanced in several areas from the previous core, providing expanded services for genetic analysis, and collection of materials and information to enable and enhance clinical trials, genotype/phenotype studies, novel gene identification, and exploration of the molecular basis of disease. Survey results indicate a high level of demand for the services to be provided. Service 1 provides access to the Mayo PKD Clinical Database that contains clinical, imaging and genetic information on a large population of PKD, especially ADPKD patients, that will facilitate association and genotype/phenotype studies. Service 2 employs locus specific approaches to screen the duplicated PKD1 gene, plus PKD2, and now includes a next generation sequencing as well as a conventional sequencing approach. This service facilitates selections of patients for clinical trials and interpretation of trial data, characterizes PKD cell-lines for the PKD community, and helps resolve the etiology of unusual patients. Service 3 complements the ADPKD oriented screening to use focused ciliopathy and whole exome approaches to screen other PKD genes for population characterization and novel gene discovery, including identifying novel ADPKD genes/modifiers. Service 4 consists of a Biobank that collects, processes and distributes tissue, cells and cyst fluid from PKD patients; an important resource to help understand pathogenesis. Service 5 involves collection and processing of urine samples from PKD patients to aid with biomarker discovery and testing. Service 6 distributes full-length clones of various cystogenes. In addition to the services, three development projects are described which aim to: 1) simplify ADPKD mutation screening and facilitate high throughput analyses; 2) generate PKD1, PKD2 and PKD1/PKD2 null cell-lines using TALEN methodologies; and 3) develop urine and plasma sample collection and processing methods to facilitate metabolomics studies. The final component of MGBC is the training aspect to disseminate the expertise of the core to investigators worldwide. Overall the core is designed to enhance genetic and biomarker PKD research and, hence, promote translational studies of these diseases.