Haplotype frequencies and linkage disequilibrium among classical HLA genes (original) (raw)
International Journal of Immunogenetics, 2012
We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of welldefined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The GENE[RATE] computer tools were combined to create a GENE[RATE] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.
International Journal of Immunogenetics
We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of welldefined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The GENE[RATE] computer tools were combined to create a GENE[RATE] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.
Tissue Antigens, 2003
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 highresolution 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.
Tissue Antigens, 1981
325 HLA-A, B and Bf haplotypes obtained from family studies were investigated. In addition, 216 of these were tested for H L A X w 2 , Cw4, Cw5. Four different statistical methods were employed to study 2, 3 or 4 loci gametic associations in order to compare the results obtained by these different methods. Our results were then compared with those of other authors who employed similar methods. Piazza's method, used to identify gametic associations, was not able to show any 3 loci associ;%tions in our material. The Delta Standard Method employed in conjunction with Factorial Correspondence Analysis was found suitable for the study of chromosal prevalence in a population.
HLA phenotype polymorphism in the lebanese population
Transfusion Clinique et Biologique, 1996
The HLA-A, -B, -DR and DQ phenotypes have been defined in a panel of 217 Lebanese. These subjects were all unrelated, belonged to different religious communities and originated from the various provinces of Lebanon. All the broad class I specificities tested, except splits A25[10), B54(221 and B56[22), were present in this panel. When HLA-A and -B antigen frequencies were compared with data on the Caucasoids, Negroids and Orientals, several similarities in antigen frequencies could be found between some frequencies observed in the Lebanese and those observed in the Negroids and/or Orientals. There were no frequencies equivalent to those particular to the Caucasoids. In addition, two groups of class I antigens could be distinguished: a first group {A32, B14, B18, B35, B38, B39, B41 and BS0) showing higher frequencies, and a second group [A31, B27, B60 and B621 showing lower frequencies than those observed in the Caucasoids, Negroids and Orientals. However, when analysed separately, several mediterranean ethnic groups, notably the Greeks and Italians, have a frequency profile equivalent to that of the Lebanese, with the exception of the B41 specificity, which is particularly high in the Lebanese [14.2 %). The data concerning the class II antigens are the most interesting. All the specificities were present in the panel. The HLA-DR5 is the highest frequency of DR antigens in the present panel [58.9 %) and nearly all DR5 positive individuals are DR11. The DRll allele accounts for 33.1% of the total DR gene frequency. The highest DQ antigen frequency is that of DQ3 [76.4 %), the majority of which is DQ¢ [66.4 %). We observed a high DR11-DQ7 haplotype frequency [29.4 %) with a significant delta value for linkage disequilibrium. There is no linkage Correspondence to: Dr Issam Mansour, Laboratoire d'Histocompatibilit6, H6tel-Dieu de France, Beirut, Lebanon. 289 290 I. MANSOUR ET AL. disequilibrium between B41 and DR11. The commonly observed linkage disequilibrium between the DQ5 allele, and the DR1, DR2, DR10 and DR14 alleles are not significant in this Lebanese panel. Polymorphisme du ph6notype HLA darts la population libanaise Les ph6notypes HLA A, B, DR et DQ ont 6t6 6tudi6es dans un 6chantillonage de 217 Libanais. Les sujets ne sont pas apparent6s et appartiennent aux diff6rentes communaut6s religieuses. Leur origine g6ographique couvre l'ensemble du Liban. Except6es les subdivisions comme A25(10}, B54(22} et B56{22), toutes les sp6cificit6s 6tudi6es en classe I sont pr6sentes dans le panel. Les fr6quences antig6niques ont 6t6 compar6es avec les Caucasoides, N6gro~des, Mongolo~des. Un premier groupe d'antig6nes HLA classe I (A32, B14, B18, B35, B38, B39, B41 et B50) a une fr6quence plus 61ev6e que celle observ6e dans ces populations, alors qu'un deuxi6me groupe (A31, B27, B60 et B62) a une fr6quence plus basse. Cependant, lorsque l'on compare les fr6quences aux groupes ethniques m6diterran6ens notamment les Grecs et les Italiens, te profil antig6nique est similaire except6 pour l'antig6ne B41 qui a une fr6quence plus 61ev6e chez les Libanais. Les r6sultats concernant les antig6nes HLA classe II sont les plus int6ressants. L'antig6ne HLA-DR5 est le plus repr6sent6 (58,9 %} et pratiquement tous les sujets DR5 sont DR11. L'all61e DR11 a une fr6quence de 33,1%. La fr6quence la plus 61ev6e au locus DQ est le DQ3 {76,4 %) dont la majorit6 des sujets sont DQ7 166,4 %}. I1 existe un d6s6quilibre de liaison DR11-DQT. Par contre, les d6s6quilibres de liaison observ6s habituellement entre DR1, DR2, DR10 et DR14 et DQ5 ne sont pas significatifs dans la population 6tudi6e. En outre, nous n'avons pas trouv6 de d6s6quilibre de liaison entre B41 et DR11.
Population Data on Two New HLA-D Determinants, El and RE
Scandinavian Journal of Immunology, 1977
Homozygous typing cells (HTC) for two new HLA-D determinants. El and RE, defined by family studies, are described. The HLA-D typing experimtens among more than 300 unrelated individuals showed phenotype frequencies of 0.045 for El and 0.098 for RE. Since the tested population was also typed for its HLA-A and -B alleles, linkage disequilibrium parameters could be calculated: HLA-D type El was statistically significantly associated with HLA-B13 and Bwl7, HLA-D type RE with HLA-Bw40. These data support the working hypothesis that both El and RE are new alleles of the HLA-D series.
Disequilibrium Pattern Analysis. II. Application to Danish HLA A and B Locus Data
Genetics, 1987
Disequilibrium pattern analysis, a general method for analyzing evolutionary events acting on pairs of tightly linked polymorphic loci, is applied to a large sample of Danish individuals typed for A and B loci of the HLA (human leukocyte antigen) system. Cases of selection on particular haplotypes are revealed from patterns of linkage disequilibrium among the HLA haplotypes. These patterns cannot be explained by either population admixture or random genetic drift. Six haplotypes out of the total array of 273 haplotypes have been identified which show in varying extents the patterns indicating selection. WO population genetic features of the HLA
Analysis of genetic interrelationship among HLA-associated diseases
American journal of human genetics, 1987
We have developed a method to study the genetic relationship between any two HLA-associated diseases. We have considered the following hypotheses: (1) both diseases are caused by a common allele; (2) different alleles at the same locus predispose to the two diseases; (3) one disease is predisposed by two alleles, one of which can also lead to the second disease; and (4) different HLA-linked loci are involved in the etiology of each disease. For each hypothesis, we have derived the expected HLA haplotype-sharing distribution in sib pairs who are affected with two diseases. The comparison of the expectations indicate that, in many cases, the alternate hypotheses can be distinguished, if the sample size is appropriately large. The knowledge of the mode of inheritance of each disease is not usually necessary; however, it can greatly increase the power of the test. Analyses of data on pairwise combinations of rheumatoid arthritis (RA), autoimmune thyroid disease (ATD), and insulin-depend...