The Heterogeneous HLA Genetic Makeup of the Swiss Population
Publication Date
July 25, 2012
Journal
PLOS ONE
Authors
Stéphane Buhler, José Manuel Nunes, Grazia Nicoloso, Jean Marie Tiercy, et al
Volume
7
Issue
7
Pages
e41400
DOI
https://dx.plos.org/10.1371/journal.pone.0041400
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0041400
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22848484
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405111
Europe PMC
http://europepmc.org/abstract/MED/22848484
Web of Science
000306806600061
Scopus
84864360313
Mendeley
http://www.mendeley.com/research/heterogeneous-hla-genetic-makeup-swiss-population
Events
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/316554", "https://ndownloader.figshare.com/files/316558", "https://ndownloader.figshare.com/files/316563", "https://ndownloader.figshare.com/files/316569", "https://ndownloader.figshare.com/files/316576", "https://ndownloader.figshare.com/files/316577", "https://ndownloader.figshare.com/files/316578", "https://ndownloader.figshare.com/files/316579", "https://ndownloader.figshare.com/files/316580", "https://ndownloader.figshare.com/files/316581", "https://ndownloader.figshare.com/files/316582"], "description"=>"<div><p>This study aims at investigating the HLA molecular variation across Switzerland in order to determine possible regional differences, which would be highly relevant to several purposes: optimizing donor recruitment strategies in hematopoietic stem cell transplantation (HSCT), providing reliable reference data in HLA and disease association studies, and understanding the population genetic background(s) of this culturally heterogeneous country. HLA molecular data of more than 20,000 HSCT donors from 9–13 recruitment centers of the whole country were analyzed. Allele and haplotype frequencies were estimated by using new computer tools adapted to the heterogeneity and ambiguity of the data. Non-parametric and resampling statistical tests were performed to assess Hardy-Weinberg equilibrium, selective neutrality and linkage disequilibrium among different loci, both in each recruitment center and in the whole national registry. Genetic variation was explored through genetic distance and hierarchical analysis of variance taking into account both geographic and linguistic subdivisions in Switzerland. The results indicate a heterogeneous genetic makeup of the Swiss population: first, allele frequencies estimated on the whole national registry strongly deviate from Hardy-Weinberg equilibrium, by contrast with the results obtained for individual centers; second, a pronounced differentiation is observed for Ticino, Graubünden, and, to a lesser extent, Wallis, suggesting that the Alps represent(ed) a barrier to gene flow; finally, although cultural (linguistic) boundaries do not represent a main genetic differentiation factor in Switzerland, the genetic relatedness between population from south-eastern Switzerland and Italy agrees with historical and linguistic data. Overall, this study justifies the maintenance of a decentralized donor recruitment structure in Switzerland allowing increasing the genetic diversity of the national—and hence global—donor registry. It also indicates that HLA data of local donor recruitment centers can be used as reference data in both epidemiological and population genetic studies focusing on the genetic history of present European populations.</p> </div>", "links"=>[], "tags"=>["heterogeneous", "hla", "swiss"], "article_id"=>122443, "categories"=>["Genetics", "Immunology", "Evolutionary Biology"], "users"=>["Stéphane Buhler", "José Manuel Nunes", "Grazia Nicoloso", "Jean-Marie Tiercy", "Alicia Sanchez-Mazas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041400.s001", "https://dx.doi.org/10.1371/journal.pone.0041400.s002", "https://dx.doi.org/10.1371/journal.pone.0041400.s003", "https://dx.doi.org/10.1371/journal.pone.0041400.s004", "https://dx.doi.org/10.1371/journal.pone.0041400.s005", "https://dx.doi.org/10.1371/journal.pone.0041400.s006", "https://dx.doi.org/10.1371/journal.pone.0041400.s007", "https://dx.doi.org/10.1371/journal.pone.0041400.s008", "https://dx.doi.org/10.1371/journal.pone.0041400.s009", "https://dx.doi.org/10.1371/journal.pone.0041400.s010", "https://dx.doi.org/10.1371/journal.pone.0041400.s011"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Heterogeneous_HLA_Genetic_Makeup_of_the_Swiss_Population/122443", "title"=>"The Heterogeneous HLA Genetic Makeup of the Swiss Population", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-07-25 00:40:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/602734"], "description"=>"<p>Only haplotypes with a frequency ≥3% in at least one recruitment region are listed. Geographic regions are indicated by different colors on the graphic: Western central plateau and Jura (light grey), Eastern central plateau and Jura (middle grey), Alps (black). AA: Aargau-Solothurn, BE: Bern, BS: Basel, GE: Genève, GR: Graubünden, LG: Lugano (Svizzera Italiana), LS: Lausanne (Vaud), LU: Luzern (Zentralschweiz), SG: St. Gallen (Nordost-Schweiz), SI: Sion (Valais) and ZH: Zürich.</p>", "links"=>[], "tags"=>["haplotype", "frequencies", "recruitment"], "article_id"=>273233, "categories"=>["Genetics", "Immunology", "Evolutionary Biology"], "users"=>["Stéphane Buhler", "José Manuel Nunes", "Grazia Nicoloso", "Jean-Marie Tiercy", "Alicia Sanchez-Mazas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041400.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_B_DRB1_haplotype_frequencies_within_each_recruitment_region_/273233", "title"=>"A-B-DRB1 haplotype frequencies within each recruitment region.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-25 00:53:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/602836"], "description"=>"<p>Symbols refer to the language spoken in each region. The stress value is 0.142 (indicating a rather good fit of the graphical representation to the original distance matrix). AA: Aargau-Solothurn, BE: Bern, BS: Basel, GE: Genève, GR: Graubünden, LG: Lugano (Svizzera Italiana), LS: Lausanne (Vaud), LU: Luzern (Zentralschweiz), SG: St. Gallen (Nordost-Schweiz), SI: Sion (Valais) and ZH: Zürich.</p>", "links"=>[], "tags"=>["scaling", "swiss", "regions", "distances", "computed", "hla", "loci", "-drb1"], "article_id"=>273322, "categories"=>["Genetics", "Immunology", "Evolutionary Biology"], "users"=>["Stéphane Buhler", "José Manuel Nunes", "Grazia Nicoloso", "Jean-Marie Tiercy", "Alicia Sanchez-Mazas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041400.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multidimensional_scaling_MDS_analysis_of_9_Swiss_regions_based_on_mean_Reynold_s_genetic_distances_computed_for_5_HLA_loci_HLA_A_B_C_DRB1_and_DQB1_/273322", "title"=>"Multidimensional scaling (MDS) analysis of 9 Swiss regions based on mean Reynold's genetic distances computed for 5 HLA loci (HLA-A, -B, -C, -DRB1 and -DQB1).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-25 00:55:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/602936"], "description"=>"<p>AA: Aargau-Solothurn, BE: Bern, BS: Basel, GE: Genève, GR: Graubünden, LG: Lugano (Svizzera Italiana), LS: Lausanne (Vaud), LU: Luzern (Zentralschweiz), SG: St. Gallen (Nordost-Schweiz), SI: Sion (Valais) and ZH: Zürich.</p>", "links"=>[], "tags"=>["13", "transfusion", "services", "sbsc", "registry", "geographic", "linguistic", "groups", "tested", "variance", "hla", "allelic", "frequencies", "supplementary", "s9"], "article_id"=>273409, "categories"=>["Genetics", "Immunology", "Evolutionary Biology"], "users"=>["Stéphane Buhler", "José Manuel Nunes", "Grazia Nicoloso", "Jean-Marie Tiercy", "Alicia Sanchez-Mazas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041400.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Map_of_the_13_regional_blood_transfusion_services_of_the_SBSC_registry_and_the_different_geographic_or_linguistic_groups_tested_by_Analysis_of_Variance_ANOVA_on_the_basis_of_HLA_allelic_frequencies_see_Supplementary_Information_S9_for_more_details_/273409", "title"=>"Map of the 13 regional blood transfusion services of the SBSC registry and the different geographic or linguistic groups tested by Analysis of Variance (ANOVA) on the basis of HLA allelic frequencies (see Supplementary Information S9 for more details).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-25 00:56:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/603035"], "description"=>"<p>Centers which are not significant after Bonferroni's correction (for the number of centers tested) are indicated within brackets. BS and ZH are not considered when B locus is involved (because of HWE rejection), as well as ZH at HLA-DRB1 for the same reasons.</p>", "links"=>[], "tags"=>["registry", "centers", "exhibiting", "gametic", "disequilibrium", "pairs", "hla"], "article_id"=>273524, "categories"=>["Genetics", "Immunology", "Evolutionary Biology"], "users"=>["Stéphane Buhler", "José Manuel Nunes", "Grazia Nicoloso", "Jean-Marie Tiercy", "Alicia Sanchez-Mazas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041400.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_List_of_registry_centers_exhibiting_significant_gametic_association_linkage_disequilibrium_LD_for_different_pairs_of_HLA_loci_/273524", "title"=>"List of registry centers exhibiting significant gametic association (linkage disequilibrium LD) for different pairs of HLA loci.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-25 00:58:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/603060"], "description"=>"<p>The meta-analysis method of Fisher has been used to compute the 5-locus combined probability for each index. Abbreviations used in the table, vs: versus, N: number of groups tested.</p>", "links"=>[], "tags"=>["indexes", "loci", "-drb1", "groups"], "article_id"=>273552, "categories"=>["Genetics", "Immunology", "Evolutionary Biology"], "users"=>["Stéphane Buhler", "José Manuel Nunes", "Grazia Nicoloso", "Jean-Marie Tiercy", "Alicia Sanchez-Mazas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041400.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Weighted_average_genetic_diversity_indexes_at_5_loci_HLA_A_B_C_DRB1_and_DQB1_within_geographic_linguistic_groups_F_SC_and_among_geographic_linguistic_groups_F_CT_/273552", "title"=>"Weighted average genetic diversity indexes at 5 loci (HLA-A, -B, -C, -DRB1 and -DQB1), within geographic/linguistic groups (F<sub>SC</sub>) and among geographic/linguistic groups (F<sub>CT</sub>).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-25 00:59:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/603099"], "description"=>"<p>Abbreviations used in the table,</p>*<p>: for 5 loci, we used a mean matrix of genetic distances and weighted average FST index with combined probability for HLA-A, -B, -C, -DRB1 and –DQB1 computed by Fisher's meta-analysis method.</p><p>CTS: regional services for blood transfusion.</p>#<p>: CF and FR not tested because of small sample sizes.</p>%<p>:: BS and ZH not included at HLA-B because of HWE rejection.</p>&<p>: ZH not included at HLA-DRB1 because of HWE rejection.</p><p>n: number of donors.</p><p>N: number of groups tested.</p><p>NA: The number of donors available at each of the 5 loci is used for the computations.</p>", "links"=>[], "tags"=>["coefficient", "matrices", "geographic", "recruitment", "centers", "hla", "locus"], "article_id"=>273587, "categories"=>["Genetics", "Immunology", "Evolutionary Biology"], "users"=>["Stéphane Buhler", "José Manuel Nunes", "Grazia Nicoloso", "Jean-Marie Tiercy", "Alicia Sanchez-Mazas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0041400.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_coefficient_r_between_matrices_of_genetic_and_geographic_distances_and_genetic_diversity_F_st_among_recruitment_centers_for_each_HLA_locus_under_study_/273587", "title"=>"Correlation coefficient (r) between matrices of genetic and geographic distances, and genetic diversity (F<sub>st</sub>) among recruitment centers for each HLA locus under study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-25 00:59:47"}

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Relative Metric

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