Cited by 179Genetic Associations and EpidemiologyRenal Transplantation Outcomes and TreatmentsHematopoietic Stem Cell Transplantation

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New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans

Klitz, W., Maiers, M., Spellman, S., Baxter‐Lowe, L.A., Schmeckpeper, B., Williams, T.M., Fernandez‐Viña, M.·2003·Tissue Antigens

DOI 10.1034/j.1399-0039.2003.00103.x

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Abstract

Abstract: A collaborative study involving a large sample of European Americans was typed for the histocompatibility loci of the HLA DR‐DQ region and subjected to intensive typing validation measures in order to accurately determine haplotype composition and frequency. The resulting tables have immediate application to HLA typing and allogeneic transplantation. The loci within the DR‐DQ region are especially valuable for such an undertaking because of their tight linkage and high linkage disequilibrium. The 3798 haplotypes, derived from 1899 unrelated individuals, had a total of 75 distinct DRB1‐DQA1‐DQB1 haplotypes. The frequency distribution of the haplotypes was right skewed with haplotypes occurring at a frequency of less than 1% numbering 59 and yet constituting less than 12% of the total sample. Given DRB1 typing, it was possible to infer the exact DQA1 and DQB1 composition of a haplotype with high confidence (>90% likelihood) in 21 of the 35 high‐resolution DRB1 alleles present in the sample. Of the DRB1 alleles without high reliability for DQ haplotype inference, only *0401, *0701 and *1302 were common, the remaining 11 DRB1 alleles constituting less than 5% of the total sample. This approach failed for the 13 serologically equivalent DR alleles in which only 33% of DQ haplotypes could be reliably inferred. The 36 DQA1‐DQB1 haplotypes present in the total sample conformed to the known pattern of permissible heterodimers. Four DQA1‐DQB1 haplotypes, all rare, are reported here for the first time. The haplotype frequency tables are suitable as a reference standard for HLA typing of the DR and DQ loci in European Americans.

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Method
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Background
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“identified in this patient represents a new DR7-DQ8 haplotype in addition to the four DR-DQ haplotypes found in a large sample of donors from different ethnic groups; i.e., DRB1*0701-DQA1*0201-DQB1*0202, DRB1*0701-DQA1*0201-DQB1*0301, DRB1*0701-DQA1*0302-DQB1*0301, and DRB1*0701-DQA1*0201-DQB1*0303 (Lin et al. 1997; K…”
Background
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BackgroundResult
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“We now performed an in-depth analysis of the ligandome of one of the most prevalent HLA-DR molecules in Caucasians, HLA-DRB1*03:01, with associated HLADRB3*02:02 molecule derived from homozygous cells (Klitz et al. 2003).”
Method
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BackgroundInfluential
CHAPTER 39 – Histocompatibility: HLA and other systems
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“PCR products were visualized by agarose-gel electrophoresis [29,30].”
Method
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MethodInfluential
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Influential
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“…haplotype frequencies (http://bioinformatics.nmdp.org/ HLA/Haplotype_Frequencies/index.html?src=review) and by other reference reports elsewhere (Klitz et al., 2003; Maiers et al., 2007; Trachtenberg et al., 2007; Yang et al., 2009), we think that the ethnicity of the donor of DL03 is probably…”
Background
Classical HLA allele and haplotype frequency estimates in US populations
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Self-citation
Evaluation of HLA-DQ Genetic Risk Classes in Pediatric Cases for Celiac Disease: Role of HLA-DQ2 and DQ8 Haplotypes
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“In the interpretation of allele levels for HLA-DQB1, detection of 0201 and 0202 was considered as positive for HLA-DQ2, and 0302 and 0305 was considered as positive for HLA-DQ8 [6].”
Immunogenetic Manifestations of Lyme Borreliosis / Imūnìenģtiskās Izpausmes Laimboreliozes Gadījumā
Kovaļčuka, L., Eglīte, J., Zīālīte, M., Lucenko, I., Vīksna, L., & Krūmiņa, A. (2016) · doi:10.1515/prolas-2016-0034 · Cited by 1
The DR7‐DQ2 Haplotype in a Native Norwegian Population
Heide, G., Stuge, T., Skogen, B., Husebekk, A., & Ahlén, M. T. (2013) · Scandinavian Journal of Immunology · doi:10.1111/sji.12031 · Cited by 1
Genetic and Environmental Pathways in Type 1 Diabetes Complications
Trucco, M. (2009) · Defense Technical Information Center (DTIC) · doi:10.21236/ada544029 · Cited by 1
No evidence for multiple loci affecting rheumatoid arthritis risk on chromosome 6p21
Sherva, R., Sun, L.-W., Biernacka, J., & Neuman, R. J. (2007) · BMC Proceedings · doi:10.1186/1753-6561-1-s1-s42 · Cited by 1
“In these cases, alleles had to be combined into broader categories to make use of the published [12] allele frequencies.”
Development of a New Third-Party Unit for Adult Stem Cell Transplantation using Clinical-Grade Rejected Cord Blood Units
Peltier, L., Brown, R., Monczak, Y., Popradi, G., Storring, J., & Laneuville, P. (2015) · doi:10.4172/2157-7412.1000254 · Cited by 1
Identification of a Distinct HLA‐DRB1*15:02–DQB1*03:01 Haplotype in a Transplant Pair
Alandejani, S. A., Saleh, N. M., Alshubaili, A., Anazi, H., & Hajeer, A. (2026) · HLA · doi:10.1111/tan.71009
Imputed HLA typing as a practical approach to molecular mismatch risk stratification in kidney transplantation
Ho, A., Vathsala, A., Sran, H., D'Costa, M., Chang, Z., Ng, A., Lim, A., Koh, W., & Wong, E. (2026) · Transplant International · doi:10.3389/ti.2026.16964
Identification of Two HLA Haplotypes Harbouring the DRB4*01:03:01:02N Null Allele and DRB1*04:02~DQ8 in the Spanish Population
Abad-Molina, C., Boix, F., Cárdaba-Arranz, M., Vilches-Moreno, M., Bustamante-Munguira, E., Eiros-Bouza, J. M., & Coca-Rojo, A. (2026) · HLA · doi:10.1111/tan.70846
A Tool for the Assessment of HLA-DQ Heterodimers Variation in Hematopoietic Cell Transplantation
Sajulga, R., Bolon, Y.-T., Maiers, M., & Petersdorf, E. (2024) · Transplantation and Cellular Therapy · doi:10.1016/j.jtct.2024.08.006
Self-citation
Investigating Associations between HLA-DR Genotype, H. pylori Infection, and Anti-CagA IgA Seropositivity in a Turkish Gastritis Cohort
Karataş, L., Tatar, Z., James, E. A., & Colakogullari, M. (2024) · Genes · doi:10.3390/genes15030339
“HLA DRB1*11:04 was co-inherited with HLA DQA1*05:05-DQB1*03:01 haplotype in 2.5% frequency among Americans of European descent [44].”
BackgroundInfluential
Correlating HLA associations with follicular lymphoma in an Australian data set: A pilot study
Sutton, E., de Santis, D., Hay, L., McKinnon, E., D'Orsogna, L. J., & Joske, D. (2020) · HLA · doi:10.1111/tan.13918
Die Dauer und Erfolgsrate der nicht-verwandten Blutstammzellspendersuche bezogen auf die HLA-DRB1-Allelhäufigkeiten und das DRB1-DQB1-Kopplungsungleichgewicht
Bloch, K. (2013) · doi:10.18725/oparu-2860
“Wegen des starken Kopplungsungleichgewichtes zwischen den zwei HLA-IIMerkmalen, können HLA-DRB1-DQB1-Haplotypen mit einer hohen Wahrscheinlichkeit nur basierend auf der hoch-aufgelösten HLA-DRB1-Typisierung vorhergesagt werden [34].”
Background
Human helper T cell responses to RSV infection
Guvenel, A. (2016) · doi:10.25560/57117

Authors: Klitz, W., Maiers, M., Spellman, S., Baxter‐Lowe, L. A., Schmeckpeper, B., Williams, T. M., & Fernandez‐Viña, M.
Affiliations: National Marrow Donor Program (US)
University of California, San Francisco (US)
American Red Cross (US)
University of New Mexico Health Sciences Center (US)
Corresponding author: Klitz, W.
ORCID: Maiers, M.
Spellman, S.
Baxter‐Lowe, L.A.
Williams, T.M.
Venue: Tissue Antigens
Publisher: Wiley
Published: 2003-09-16
Volume: 62
Issue: 4
Pages: 296-307
ISSN: 0001-2815 (ISSN-L)
1399-0039
DOI: 10.1034/j.1399-0039.2003.00103.x
OpenAlex: W1976319355
Cited by: 179
References: 0
Citations by year: 2026: 5 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 1 · 2021: 9 · 2020: 9 · 2019: 4 · 2018: 6 · 2017: 11 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 8 · 2012: 12
FWCI: 3.89
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Tissue Antigens (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords: HLA haplotype frequencies, HLA-DRB1, HLA-DQA1, HLA-DQB1, haplotype inference, linkage disequilibrium, European Americans, allogeneic transplantation, rare haplotypes
MeSH terms: Histocompatibility Antigens Class II, Gene Frequency, Haplotypes, Histocompatibility Testing, HLA-DQ Antigens, HLA-DR Antigens, Humans, Reference Standards, HLA-A Antigens, HLA-B Antigens, White People, HLA-DRB1 Chains, HLA-DQ alpha-Chains, HLA-DQ beta-Chains

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New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans

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