Journal ArticleDOI
Regional differences in HLA antigen and haplotype frequency distributions in Germany and their relevance to the optimization of hematopoietic stem cell donor recruitment.
Alexander H. Schmidt,Ute V. Solloch,Daniel M. Baier,A Stahr,Ralf Wassmuth,Gerhard Ehninger,Claudia Rutt +6 more
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TLDR
Analysis of genetic distances suggests the existence of three regional clusters in South (regions 6-9), East (0-1), and Northwest (2-5) Germany, which shows most favorable characteristics with respect to haplotypic and phenotypic diversity and the occurrence of rare HLA antigens.Abstract:
We analyzed regional differences in human leukocyte antigen (HLA)-A, -B, and -DR antigen and haplotype frequencies based on a sample of approximately 320,000 German donors in order to identify regions that are especially suited for ongoing stem cell donor recruitment. Geographic partitioning was carried out by postal code regions. Analysis of genetic distances suggests the existence of three regional clusters in South (regions 6-9), East (0-1), and Northwest (2-5) Germany. The southern cluster shows most favorable characteristics with respect to haplotypic and phenotypic diversity and the occurrence of rare HLA antigens. The opposite behavior is shown by regions 2-4 of the northwestern cluster. As a result of lower HLA diversity, completeness of a regional donor file in region 4 with 100,000 donors would be higher than that of a file in region 7 with 170,000 donors. This fact shows the relevance of regional HLA differences for practical donor registry planning. Results such as those presented in this work can be used to diminish the problem of decreasing marginal benefit of donor recruitment, as more than 13 million donors are registered worldwide today.read more
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Frequencies of gene variant CCR5-Δ32 in 87 countries based on next-generation sequencing of 1.3 million individuals sampled from 3 national DKMS donor centers.
TL;DR: The characteristic CCR5-Δ32 allele frequency decline from Northern to Southeastern Eurasia supports findings of earlier studies and allows upfront estimation of the probability that an HLA-matched donor with C CR5- Δ32/Δ 32 genotype can be found for a patient in need of hematopoietic stem cell transplantation.
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High-resolution HLA haplotype frequencies of stem cell donors in Germany with foreign parentage: how can they be used to improve unrelated donor searches?
Julia Pingel,Ute V. Solloch,Jan A. Hofmann,Vinzenz Lange,Gerhard Ehninger,Alexander H. Schmidt +5 more
TL;DR: It is demonstrated how genetic differences between populations are reflected in matching probabilities of recipient/donor pairs and how they influence the search for unrelated donors as well as strategic donor center typings.
Journal ArticleDOI
Haplotype-Based Banking of Human Pluripotent Stem Cells for Transplantation: Potential and Limitations
TL;DR: To minimize the risk of rejection, human leukocyte antigen (HLA) compatibility is certainly the best option, and the establishment of an HLA-organized bank would mean having a limited number of stem cells that would be sufficient for a large number of recipients.
Journal ArticleDOI
HLA-DRB1*15:01 and multiple sclerosis: a female association?:
Haritz Irizar,Maider Muñoz-Culla,Olaia Zuriarrain,Estibaliz Goyenechea,Tamara Castillo-Triviño,Alvaro Prada,Matías Sáenz-Cuesta,Dolores De Juan,Adolfo López de Munain,Javier Olascoaga,David Otaegui +10 more
TL;DR: The data confirms that the *15:01 haplotype confers a higher risk of suffering from MS and support that it is female specific and no association was found between VDR variants and MS, but they were shown to moderately modulate the risk conferred by * 15:01.
Journal ArticleDOI
Beating the odds: factors implicated in the speed and availability of unrelated haematopoietic cell donor provision
TL;DR: In this paper, the authors identified a key source of delay for unrelated haematopoietic cell (HPC) donors, and developed a number of strategies designed to minimise delays and, ultimately, improve patient outcomes.
References
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Journal ArticleDOI
Arlequin (version 3.0): An integrated software package for population genetics data analysis
TL;DR: Arlequin ver 3.0 as discussed by the authors is a software package integrating several basic and advanced methods for population genetics data analysis, like the computation of standard genetic diversity indices, the estimation of allele and haplotype frequencies, tests of departure from linkage equilibrium, departure from selective neutrality and demographic equilibrium, estimation or parameters from past population expansions, and thorough analyses of population subdivision under the AMOVA framework.
Journal ArticleDOI
Measurement of diversity
TL;DR: In this article, the authors define and examine a measure of concentration in terms of population constants, and examine the relationship between the characteristic and the index of diversity when both are applied to a logarithmic distribution.
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Phylogenetic analysis. Models and estimation procedures.
TL;DR: This paper shows how suitable evolutionary models can be constructed and applied objectively and how the type of data will affect both the method of treatment and the validity of the results.
Journal ArticleDOI
High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation.
Stephanie J. Lee,John P. Klein,Michael Haagenson,Lee Ann Baxter-Lowe,Dennis L. Confer,Mary Eapen,Marcelo Fernandez-Vina,Neal Flomenberg,Mary M. Horowitz,Carolyn Katovich Hurley,Harriet Noreen,Machteld Oudshoorn,Effie W. Petersdorf,Michelle Setterholm,Stephen R. Spellman,Daniel J. Weisdorf,Thomas M. Williams,Claudio Anasetti +17 more
TL;DR: In multivariate modeling, patient age, race, disease stage, and cytomegalovirus status were as predictive of survival as donor HLA matching, and high-resolution DNA matching for HLA-A, -B, -C, and -DRB1 alleles is associated with higher rates of survival.
Journal ArticleDOI
Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age
Craig Kollman,Craig W. S. Howe,Claudio Anasetti,Joseph H. Antin,Stella M. Davies,Alexandra H. Filipovich,J Hegland,Naynesh Kamani,Nancy A. Kernan,Roberta King,Voravit Ratanatharathorn,Daniel J. Weisdorf,Dennis L. Confer +12 more
TL;DR: Age should be considered when selecting among comparably HLA-matched volunteer donors and the use of younger donors may lower the incidence of GVHD and improve survival after bone marrow transplantation.
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