A high-throughput population screening system for the estimation of genetic risk for type 1 diabetes: An application for the TEDDY (The Environmental Determinants of Diabetes in the Young) study

Minna Kiviniemi, Robert Hermann, Jussi Nurmi, Anette G. Ziegler, Mikael Knip, Olli Simell, Riitta Veijola, Timo Lövgren, Jorma Ilonen, Marian Rewers, Katherine Barriga, Judith Baxter, Ann Deas, George Eisenbarth, Lisa Emery, Patricia Gesualdo, Michelle Hoffman, Jill Norris, Kathleen Waugh, Stacey WeberJin-Xiong She, Andy Muir, Desmond Schatz, Diane Hopkins, Leigh Steed, Angela Choate, Katherine Silvis, Meena Shankar, Yi Hua Huang, Ping Yang, Wei Peng Zheng, Hong Jie Wang, Kim English, Richard A McIndoe, Ezio Bonifacio, Andrea Baumgarten, Sandra Hummel, Mathilde Kersting, Stephanie Koenig, Annette Knopff, Angelika Locher, Roswith Roth, Stefanie Schoen, Petra Schwaiger, Wolfgang Sichert-Hellert, Christiane Winkler, Diana Zimmermann, Kirsti Nanto-Salonen, Tuula Simell, Ulla Uusitalo, Heikki Hyöty, Suvi M. Virtanen, Carina Kronberg-Kippilä, Maija Torma, Eeva Ruohonen, Minna Romo, Elina Mantymaki, Tiina Niininen, Mia Nyblom, Aino Stenius, Åke Lernmark, Peter Almgren, Carin Andrén-Aronsson, Eva Andersson, Sylvia Bianconi-Svensson, Ulla Marie Carlsson, Corrado Cilio, Joanna Gerardsson, Barbro Gustavsson, Anna Hansson, Gertie Hansson, Ida Hansson, Sten Ivarsson, Helena Larsson, Elli Karlsson, Anastasia Katsarou, Barbro Lernmark, Thea Massadakis, Anita Nilsson, Monica Sedig Järvirova, Birgitta Sjöberg, Anne Wallin, Åsa Wimar, William A. Hagopian, Michael Brantley, Claire Cowen, Peng Hui, Kristen M. Hay, Melissa Jackson, Viktoria Stepikova, Jennifer Ugale, Jeffrey P. Krischer, Carole Bray, David Cuthbertson, Veena Gowda, Kimberly Hunt, Shu Liu, Jamie Malloy, Cristina McCarthy, Wendy McLeod, Susan Moyers, Lavanya Nallamshetty, Susan Smith, Beena Akolkar, Thomas Briese, Henry Erlich, Suzanne Bennett Johnson, Steve Oberste

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Abstract

Background: In the TEDDY (The Environmental Determinants of Diabetes in the Young) study patient eligibility is based on the presence of some selected type 1 diabetes risk-associated human leukocyte antigen DR-DQ genotypes. A practical screening strategy was needed with efficient exclusion of ineligible patients at an early stage. Also, a simple, low-cost, and fast screening system was essential for the primary step of the risk assessment including thousands of samples. Methods: A homogeneous genotyping system utilizing an asymmetric polymerase chain reaction (PCR) and subsequent hybridization of allele-specific probes was designed to be used as the first screening step. This assay was combined with methods further elucidating the genetic risk of type 1 diabetes to screen for high-risk individuals. Results: The homogeneous assay platform allows the typing of hundreds of samples within one working day. The costs of the assay are minimal, and the reduction in hands-on time provides considerable improvements compared to the heterogeneous genotyping methods comprising separate PCR and hybridization steps. The primary selection criteria used in the first step proved to be efficient since the numbers of samples typed in subsequent stages were markedly reduced. Conclusions: The presented assay system provides a practical approach to the rapid screening of thousands of samples at low cost, a general starting point for large-scale screening studies.

Original languageEnglish (US)
Pages (from-to)460-472
Number of pages13
JournalDiabetes Technology and Therapeutics
Volume9
Issue number5
DOIs
StatePublished - Oct 1 2007

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Medical Laboratory Technology

Cite this

Kiviniemi, M., Hermann, R., Nurmi, J., Ziegler, A. G., Knip, M., Simell, O., Veijola, R., Lövgren, T., Ilonen, J., Rewers, M., Barriga, K., Baxter, J., Deas, A., Eisenbarth, G., Emery, L., Gesualdo, P., Hoffman, M., Norris, J., Waugh, K., ... Oberste, S. (2007). A high-throughput population screening system for the estimation of genetic risk for type 1 diabetes: An application for the TEDDY (The Environmental Determinants of Diabetes in the Young) study. Diabetes Technology and Therapeutics, 9(5), 460-472. https://doi.org/10.1089/dia.2007.0229