The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

HLA genotyping in the international Type 1 Diabetes Genetics Consortium

På svenska

Author

  • Josyf C. Mychaleckyj
  • Janelle A. Noble
  • Priscilla V. Moonsamy
  • Joyce Carlson
  • Michael D. Varney
  • Jeff Post
  • Wolfgang Helmberg
  • June J. Pierce
  • Persia Bonella
  • Anna Lisa Fear
  • Eva Lavant
  • Anthony Louey
  • Sean Boyle
  • Julie A. Lane
  • Paul Sali
  • Samuel Kim
  • Rebecca Rappner
  • Dustin T. Williams
  • Letitia H. Perdue
  • David M. Reboussin
  • Brian D. Tait
  • Beena Akolkar
  • Joan E. Hilner
  • Michael W. Steffes
  • Henry A. Erlich
Show all

Summary, in English

Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers. Purpose In this article, we present the operational strategy of training, classification, reporting, and quality control of HLA genotyping in four laboratories on three continents over nearly 5 years. Methods Methods to standardize HLA genotyping at eight loci included: central training and initial certification testing; the use of uniform reagents, protocols, instrumentation, and software versions; an automated data transfer; and the use of standardized nomenclature and allele databases. We implemented a rigorous and consistent quality control process, reinforced by repeated workshops, yearly meetings, and telephone conferences. Results A total of 15,246 samples have been HLA genotyped at eight loci to four-digit resolution; an additional 6797 samples have been HLA genotyped at two loci. The genotyping repeat rate decreased significantly over time, with an estimated unresolved Mendelian inconsistency rate of 0.21%. Annual quality control exercises tested 2192 genotypes (4384 alleles) and achieved 99.82% intra-laboratory and 99.68% inter-laboratory concordances. Limitations The chosen genotyping platform was unable to distinguish many allele combinations, which would require further multiple stepwise testing to resolve. For these combinations, a standard allele assignment was agreed upon, allowing further analysis if required. Conclusions High-resolution HLA genotyping can be performed in multiple laboratories using standard equipment, reagents, protocols, software, and communication to produce consistent and reproducible data with minimal systematic error. Many of the strategies used in this study are generally applicable to other large multi-center studies. Clinical Trials 2010; 7: S75-S87. http://ctj.sagepub.com.

Publishing year

2010

Language

English

Pages

75-87

Publication/Series

Clinical Trials

Volume

7

Issue

1 suppl.

Document type

Journal article

Publisher

SAGE Publications

Topic

  • Medicinal Chemistry

Status

Published

Research group

  • Clinical Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1740-7753