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)
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Special Emphasis Panel (ZDK1-GRB-G)
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Duke University
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Tsai, I-Chun; McKnight, Kelly; McKinstry, Spencer U et al. (2018) Small molecule inhibition of RAS/MAPK signaling ameliorates developmental pathologies of Kabuki Syndrome. Sci Rep 8:10779
Sanna-Cherchi, Simone; Khan, Kamal; Westland, Rik et al. (2017) Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations. Am J Hum Genet 101:789-802
Lopez-Rivera, Esther; Liu, Yangfan P; Verbitsky, Miguel et al. (2017) Genetic Drivers of Kidney Defects in the DiGeorge Syndrome. N Engl J Med 376:742-754
Frosk, Patrick; Arts, Heleen H; Philippe, Julien et al. (2017) A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis. J Med Genet 54:490-501
Shaw, Natalie D; Brand, Harrison; Kupchinsky, Zachary A et al. (2017) SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome. Nat Genet 49:238-248
Loviglio, Maria Nicla; Arbogast, Thomas; Jønch, Aia Elise et al. (2017) The Immune Signaling Adaptor LAT Contributes to the Neuroanatomical Phenotype of 16p11.2 BP2-BP3 CNVs. Am J Hum Genet 101:564-577
Ta-Shma, Asaf; Khan, Tahir N; Vivante, Asaf et al. (2017) Mutations in TMEM260 Cause a Pediatric Neurodevelopmental, Cardiac, and Renal Syndrome. Am J Hum Genet 100:666-675
Ozantürk, Ay?egül; 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
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
Katsanis, Nicholas (2016) The continuum of causality in human genetic disorders. Genome Biol 17:233

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