PMID- 20595243
OWN - NLM
STAT- MEDLINE
DCOM- 20110307
LR  - 20211020
IS  - 1740-7753 (Electronic)
IS  - 1740-7745 (Print)
IS  - 1740-7745 (Linking)
VI  - 7
IP  - 1 Suppl
DP  - 2010
TI  - HLA genotyping in the international Type 1 Diabetes Genetics Consortium.
PG  - S75-87
LID - 10.1177/1740774510373494 [doi]
AB  - 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.
FAU - Mychaleckyj, Josyf C
AU  - Mychaleckyj JC
AD  - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 
      USA.
FAU - Noble, Janelle A
AU  - Noble JA
FAU - Moonsamy, Priscilla V
AU  - Moonsamy PV
FAU - Carlson, Joyce A
AU  - Carlson JA
FAU - Varney, Michael D
AU  - Varney MD
FAU - Post, Jeff
AU  - Post J
FAU - Helmberg, Wolfgang
AU  - Helmberg W
FAU - Pierce, June J
AU  - Pierce JJ
FAU - Bonella, Persia
AU  - Bonella P
FAU - Fear, Anna Lisa
AU  - Fear AL
FAU - Lavant, Eva
AU  - Lavant E
FAU - Louey, Anthony
AU  - Louey A
FAU - Boyle, Sean
AU  - Boyle S
FAU - Lane, Julie A
AU  - Lane JA
FAU - Sali, Paul
AU  - Sali P
FAU - Kim, Samuel
AU  - Kim S
FAU - Rappner, Rebecca
AU  - Rappner R
FAU - Williams, Dustin T
AU  - Williams DT
FAU - Perdue, Letitia H
AU  - Perdue LH
FAU - Reboussin, David M
AU  - Reboussin DM
FAU - Tait, Brian D
AU  - Tait BD
FAU - Akolkar, Beena
AU  - Akolkar B
FAU - Hilner, Joan E
AU  - Hilner JE
FAU - Steffes, Michael W
AU  - Steffes MW
FAU - Erlich, Henry A
AU  - Erlich HA
CN  - T1DGC
LA  - eng
GR  - R01 DK061722/DK/NIDDK NIH HHS/United States
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100701
PL  - England
TA  - Clin Trials
JT  - Clinical trials (London, England)
JID - 101197451
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Algorithms
MH  - Biological Assay
MH  - Clinical Laboratory Techniques
MH  - Diabetes Mellitus, Type 1/epidemiology/*genetics
MH  - Education
MH  - *Genotype
MH  - Global Health
MH  - HLA Antigens/analysis/*genetics
MH  - Humans
MH  - *International Cooperation
MH  - Pedigree
MH  - Polymorphism, Genetic
MH  - Quality Control
MH  - Risk Assessment
PMC - PMC2917849
EDAT- 2010/07/03 06:00
MHDA- 2011/03/08 06:00
PMCR- 2010/08/09
CRDT- 2010/07/03 06:00
PHST- 2010/07/03 06:00 [entrez]
PHST- 2010/07/03 06:00 [pubmed]
PHST- 2011/03/08 06:00 [medline]
PHST- 2010/08/09 00:00 [pmc-release]
AID - 1740774510373494 [pii]
AID - 10.1177_1740774510373494 [pii]
AID - 10.1177/1740774510373494 [doi]
PST - ppublish
SO  - Clin Trials. 2010;7(1 Suppl):S75-87. doi: 10.1177/1740774510373494. Epub 2010 Jul 
      1.