- Email: [email protected]
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Abstracts / Human Immunology 74 (2013) 51–173
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EXTENDED B⁄73 HAPLOTYPES CONFIRMED BY FAMILY STUDIES. Lois E. Regen 1, Reena Patel 1, Debra Cordell 1, Shalini E. Pereira 1,2,3. 1 Clinical Immunogenetics Laboratory, Seattle Cancer Care Alliance, Seattle, WA, USA; 2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 3 Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. Aim: The B⁄73:01 allele has been a subject of interest since the mid-1990’s, when it was recognized as defining its own lineage, separate from all other HLA-B alleles (Parham et al). Recently, B⁄73 has been implicated in the evolution of the Denisovans, an archaic human group, despite the fact that it has not yet been found in a Denisovan specimen (Abi-Rached et al). The theory that B⁄73 haplotypes were acquired by introgression from Denisovans prompted us to search our current clinical database for extended B⁄73 haplotypes, as demonstrated by family studies. Methods: We searched our clinical database for any patients or family members that had been typed as B⁄73 and looked for extended haplotypes which were confirmed within each family. Results: From January 2000 to February 2013, a total of 10 families were identified with extended B⁄73 haplotypes (Table 1). Four families had the haplotype A⁄02:01, C⁄15:05, B⁄73:01, DRB1⁄04:05, DQB1⁄02:02. The six remaining families had unique extended haplotypes. C⁄15:05 was present in every haplotype.[Table 1] Conclusions: Despite the diversity of the B⁄73 haplotypes, in every case B⁄73:01 was in strong linkage disequilibrium with C⁄15:05. This was expected, because it has been estimated that worldwide, 98% of people carrying B⁄73 also carry C⁄15:05 (Abi-Rached et al). The only Denisovan individual who has been HLA typed was C⁄15:05:02, C⁄12:02:02, but lacked a B⁄73:01 allele and was typed as B⁄15:58, B⁄35:63. It will be interesting to see if Class II typing for this archaic sample corresponds to any of the Class II alleles in the extended haplotypes in this study.
Pub #: 155-P Order: 1
Table 1
B⁄73 Haplotypes 4 1 1 1 1 1 1
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Famiilies Family Family Family Family Family Family
A⁄0201 A⁄0201 A⁄0103 A⁄0103 A⁄0103 A⁄0301 A⁄3201
C⁄1505 C⁄1505 C⁄1505 C⁄1505 C⁄1505 C⁄1505 C⁄1505
B⁄7301 B⁄7301 B⁄7301 B⁄7301 B⁄7301 B⁄7301 B⁄7301
DRB1⁄0405 DRB1⁄1302 DRB1⁄1001 DRB1⁄1501 DRB1⁄1501 DRB1⁄1001 DRB1⁄0804
QB1⁄0202 QB1⁄0604 QB1⁄0501 QB1⁄0502 QB1⁄0602 QB1⁄0501 QB1⁄0402
2 Cauc/2 Hisp Cauc North African Cauc Hisp North African Native Amer
POPULATION STUDY OF HÉMA-QUÉBEC STEM CELL DONOR REGISTRY. Lucie Richard 1, Stéphane Buhler 2, José M. Nunes 2, Alicia Sanchez-Mazas 2. 1 Reference and Stem Cell Laboratory, Héma-Québec, Saint-Laurent, QC, Canada; 2 Department of Genetics and Evolution - Anthropology Unit, University of Geneva, Geneva, Switzerland. Aim: Under both COST Action BM0803 (HLA-NET) and the Analysis of Human Population Data (AHPD) component of the 15th and 16th International HLA and Immunogenetics Workshops, we analyzed the Héma-Québec registry. Our aim was to verify whether a genetic heterogeneity at the country level could result in a stratification of the donor’s genetic diversity according to distinct geographic areas. Methods: The HLA-A, -B and -DRB1 molecular typings available for almost 13,000 bone marrow donors from Quebec were analyzed, using postal codes for their geographic location. For HLA-A and -B, the results were reported as generic (e.g. A⁄02:XX). For HLA-DRB1, the picture was more complex with variable proportions of unambiguous, ambiguous and generic data. These data were pre-processed using SPLIT-TEST and analyzed using GENE[RATE] and additional tools. Hardy-Weinberg equilibrium (HWE) was assessed using a nested likelihood procedure. An extended version of the classical Ewens-Watterson (EW) test accommodating ambiguous data was used to test for departures from neutral expectations. Global linkage disequilibrium was tested with a resampling procedure. Reynolds’ genetic distances were computed between regions and plotted by PCoA. SAMOVA analyses were performed to identify possible genetic boundaries across Quebec. Results: When taking Quebec as a whole, highly significant deviations from HWE are observed for HLA-B and -DRB1. A very distinct profile is observed at the regional level, with all regions being under HWE, except Montréal. Significant linkage disequilibrium could be demonstrated for B-DRB1 in some regions. Estimation of genetic distance shows that some regions like Saguenay and Gaspésie are clearly differentiated from the others. Conclusions: Donor population subdivision was found to be significant. Intra- and inter-regional analyses characterized more precisely the patterns of HLA variation in Quebec. These observations support that current donor distribution reflects an existing regional diversity.
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EXTENDED B⁄73 HAPLOTYPES CONFIRMED BY FAMILY STUDIES. Lois E. Regen 1, Reena Patel 1, Debra Cordell 1, Shalini E. Pereira 1,2,3. 1 Clinical Immunogenetics Laboratory, Seattle Cancer Care Alliance, Seattle, WA, USA; 2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 3 Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. Aim: The B⁄73:01 allele has been a subject of interest since the mid-1990’s, when it was recognized as defining its own lineage, separate from all other HLA-B alleles (Parham et al). Recently, B⁄73 has been implicated in the evolution of the Denisovans, an archaic human group, despite the fact that it has not yet been found in a Denisovan specimen (Abi-Rached et al). The theory that B⁄73 haplotypes were acquired by introgression from Denisovans prompted us to search our current clinical database for extended B⁄73 haplotypes, as demonstrated by family studies. Methods: We searched our clinical database for any patients or family members that had been typed as B⁄73 and looked for extended haplotypes which were confirmed within each family. Results: From January 2000 to February 2013, a total of 10 families were identified with extended B⁄73 haplotypes (Table 1). Four families had the haplotype A⁄02:01, C⁄15:05, B⁄73:01, DRB1⁄04:05, DQB1⁄02:02. The six remaining families had unique extended haplotypes. C⁄15:05 was present in every haplotype.[Table 1] Conclusions: Despite the diversity of the B⁄73 haplotypes, in every case B⁄73:01 was in strong linkage disequilibrium with C⁄15:05. This was expected, because it has been estimated that worldwide, 98% of people carrying B⁄73 also carry C⁄15:05 (Abi-Rached et al). The only Denisovan individual who has been HLA typed was C⁄15:05:02, C⁄12:02:02, but lacked a B⁄73:01 allele and was typed as B⁄15:58, B⁄35:63. It will be interesting to see if Class II typing for this archaic sample corresponds to any of the Class II alleles in the extended haplotypes in this study.
Pub #: 155-P Order: 1
Table 1
B⁄73 Haplotypes 4 1 1 1 1 1 1
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Famiilies Family Family Family Family Family Family
A⁄0201 A⁄0201 A⁄0103 A⁄0103 A⁄0103 A⁄0301 A⁄3201
C⁄1505 C⁄1505 C⁄1505 C⁄1505 C⁄1505 C⁄1505 C⁄1505
B⁄7301 B⁄7301 B⁄7301 B⁄7301 B⁄7301 B⁄7301 B⁄7301
DRB1⁄0405 DRB1⁄1302 DRB1⁄1001 DRB1⁄1501 DRB1⁄1501 DRB1⁄1001 DRB1⁄0804
QB1⁄0202 QB1⁄0604 QB1⁄0501 QB1⁄0502 QB1⁄0602 QB1⁄0501 QB1⁄0402
2 Cauc/2 Hisp Cauc North African Cauc Hisp North African Native Amer
POPULATION STUDY OF HÉMA-QUÉBEC STEM CELL DONOR REGISTRY. Lucie Richard 1, Stéphane Buhler 2, José M. Nunes 2, Alicia Sanchez-Mazas 2. 1 Reference and Stem Cell Laboratory, Héma-Québec, Saint-Laurent, QC, Canada; 2 Department of Genetics and Evolution - Anthropology Unit, University of Geneva, Geneva, Switzerland. Aim: Under both COST Action BM0803 (HLA-NET) and the Analysis of Human Population Data (AHPD) component of the 15th and 16th International HLA and Immunogenetics Workshops, we analyzed the Héma-Québec registry. Our aim was to verify whether a genetic heterogeneity at the country level could result in a stratification of the donor’s genetic diversity according to distinct geographic areas. Methods: The HLA-A, -B and -DRB1 molecular typings available for almost 13,000 bone marrow donors from Quebec were analyzed, using postal codes for their geographic location. For HLA-A and -B, the results were reported as generic (e.g. A⁄02:XX). For HLA-DRB1, the picture was more complex with variable proportions of unambiguous, ambiguous and generic data. These data were pre-processed using SPLIT-TEST and analyzed using GENE[RATE] and additional tools. Hardy-Weinberg equilibrium (HWE) was assessed using a nested likelihood procedure. An extended version of the classical Ewens-Watterson (EW) test accommodating ambiguous data was used to test for departures from neutral expectations. Global linkage disequilibrium was tested with a resampling procedure. Reynolds’ genetic distances were computed between regions and plotted by PCoA. SAMOVA analyses were performed to identify possible genetic boundaries across Quebec. Results: When taking Quebec as a whole, highly significant deviations from HWE are observed for HLA-B and -DRB1. A very distinct profile is observed at the regional level, with all regions being under HWE, except Montréal. Significant linkage disequilibrium could be demonstrated for B-DRB1 in some regions. Estimation of genetic distance shows that some regions like Saguenay and Gaspésie are clearly differentiated from the others. Conclusions: Donor population subdivision was found to be significant. Intra- and inter-regional analyses characterized more precisely the patterns of HLA variation in Quebec. These observations support that current donor distribution reflects an existing regional diversity.