It is vital to the activities of our Center that the investigative team is positioned to a) rapidly and securely archive biological samples from patients to enable the identification of pathogenic variants, and b) use primary patient material to explore the functional consequences of those variants. Core B will accomplish both of these goals. This Core will build on the capabilities of two existing Duke School of Medicine Shared Resources: the Center for Human Genetics (CHG) Biobank, and the Duke Induced Pluripotent Stem Cell (IPS) Core facility. As patients are identified in Project 1 and recruited to the study, biospecimens will be collected from them and their willing family members. Samples can take different forms, as determined by availability and opportunities during clinical procedures without additional burden to the patient. They may include cord blood, excess blood remaining from clinical draws, or tissue samples such as chorionic villi or foreskin fibroblasts. This material will be processed to yield both extracted DNA and primary cell cultures that subsequently will be used to generate a variety of transformed cell lines, including induced pluripotent (IPS) cells. The DNA will be used for whole exome sequencing and Sanger follow-up of specific candidate variants. As candidate pathogenic variants are identified, functional analyses will be initiated. The cell lines generated will be an integral resource since they are expected, in some instances, to provide a potential source of physiologically-relevant cell types for testing gene function. Importantly, although there are currently no straightforward protocols for differentiating IPS and hESCs into kidney epithelium this may become possible in the future. Meanwhile, assays for the effects of mutations on properties such as cell polarity, cell-cell adhesion and barrier formation could be carried out using simple epithelial derived from IPS cells in culture. Through the collaboration of Core B and Project 2 or Project 3 investigators, cell lines can be propagated and the Core will assist with the implementation of protocols to differentiate iPS cells into a multiple tissue types, thus expanding the cell and tissue repertoire in which we can explore the effects of genetic variants.

Public Health Relevance

The ability to biobank both DNA samples and tissue material from patients enrolled in our Center are critical to our activities. Core B will provide such support, as well as education and training on the emergent field of IPS reprogramming, a critical component to the generation of physiologically relevant assays to study genetic variation.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-G)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
United States
Zip Code
Bolar, Nikhita Ajit; Golzio, Christelle; Živná, Martina et al. (2016) Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia. Am J Hum Genet 99:174-87
Ozantürk, Ayşegül; Davis, Erica E; Sabo, Aniko et al. (2016) A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay. Cold Spring Harb Mol Case Stud 2:a000703
Lindstrand, Anna; Frangakis, Stephan; Carvalho, Claudia M B et al. (2016) Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome. Am J Hum Genet 99:318-36
Katsanis, Nicholas (2016) The continuum of causality in human genetic disorders. Genome Biol 17:233
Angrist, Misha (2015) Start me up: ways to encourage sharing of genomic information with research participants. Nat Rev Genet 16:435-6
Anderson, Blair R; Howell, David N; Soldano, Karen et al. (2015) In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress. PLoS Genet 11:e1005349
Burrage, Lindsay C; Charng, Wu-Lin; Eldomery, Mohammad K et al. (2015) De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome. Am J Hum Genet 97:904-13
Bögershausen, Nina; Tsai, I-Chun; Pohl, Esther et al. (2015) RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome. J Clin Invest 125:3585-99
Bonora, Elena; Bianco, Francesca; Cordeddu, Lina et al. (2015) Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction. Gastroenterology 148:771-782.e11
Isrie, Mala; Breuss, Martin; Tian, Guoling et al. (2015) Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type. Am J Hum Genet 97:790-800

Showing the most recent 10 out of 24 publications