African‐American HLA class II allele and haplotype diversity

Just, Jeanette J.; King, Mary Claire; Thomson, Glenys; Klitz, William

doi:10.1111/j.1399-0039.1997.tb02801.x

Cited by 53 publications

(12 citation statements)

References 27 publications

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“…Apart from the top 10 alleles listed in Table 3, others like A*3101, A*3201, A*68(01/02), B*1302, B*5101, and B*5701 also ranked high, with frequencies ranging from 0.020 to 0.035. In the same 100 amplified (F29 processed) DNA samples, common MICA alleles (Table 3) (Table 3) were consistent with their frequent presence in native Africans (30,32,33).…”

Section: Initial Tests Using Cell Line Dnasupporting

confidence: 55%

Molecular typing of human leukocyte antigen and related polymorphisms following whole genome amplification

Shao¹,

Tang²,

Dorak³

et al. 2004

Human Immunology

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DNA samples with suboptimal quality or limited quantity often compromise reliable, high-resolution HLA typing. We tested the feasibility of molecular typing for variants at HLA and neighboring loci using whole genome amplification (WGA) strategy facilitated by the Phi29 DNA polymerase. With little ( 50 ng) starting material, amplified DNA provided adequate templates for PCR-based genotyping of several HLA (A, B, C, DRB1, and DQB1) and related loci (HFE, MICA, and 10 microsatellites). The PCR amplicons ranged from 92 to 2,200 bp, and genotyping was performed successfully using several techniques including amplification size polymorphism, PCR with sequence-specific primers, restriction fragment length polymorphism, reference strand-mediated conformation analysis, and sequencing-based typing. In our analyses of 47 cell lines and 122 DNA specimens from native Africans and European Americans, a total of 321 genotypes have been confirmed by typing both original and amplified DNA. Additional genotyping using amplified (Phi29 processed) DNA alone produced results that were consistent with known patterns of allelic distribution and linkage disequilibrium observed in highly comparable populations. Thus, WGA appeared to provide a reliable and simple approach to securing ample genomic DNA for a variety of genotyping schemes. DNA-based typing often requires separate analysis of closely related alleles or genes, to resolve di-allelic ambiguities. Allele or group specific amplification or physical separation can be used to achieve allele separation for haploid analysis. As an alternative, we used peptide nucleic acids (PNAs) to achieve specific blockade of one of a pair of alleles during amplification. PNAs are hybrid synthetic molecules composed of nucleotide bases on a peptide backbone. PNAs retain the ability to hybridize to single-stranded nucleic acids, with greater affinity than complementary DNA. PNAs can specifically block amplification either by competing for primer annealing sites, or inhibiting polymerase extension by annealing between the primers. We designed PNA oligomers with exact complementarity to HLA Class I and II sequences. To maximize the diversity of potential annealing sites, the PNA sequences were directed to polymorphic exon motifs located between the amplification primers. HLA alleles were typed using standard procedures, and ambiguous samples were selected for re-amplification in the presence of a PNA complementary to one of the allele groups. The PNAcontaining reactions consisted of standard PCR reagents with the same profiles except for an added PNA annealing step. The PNA concentration was optimized empirically for each PNA and required from 0.5 to 10 uM for complete inhibition. After PNA-inhibited amplification, excess primers, PNA and nucleotides were removed, and the DNA was sequenced. We have blocked HLA-A, HLA-B and HLA-DR alleles using this technique. We conclude that PNAs can be used to achieve haploid amplification and eliminate ambiguities that result from cis/trans uncertainty in commonly...

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Section: Initial Tests Using Cell Line Dnasupporting

confidence: 55%

Molecular typing of human leukocyte antigen and related polymorphisms following whole genome amplification

Shao¹,

Tang²,

Dorak³

et al. 2004

Human Immunology

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“…DRB1-DQA1-DQB1 haplotypes could be unequivocally determined in the 36 diabetic subjects with a family member and in subjects homozygous for at least two of the DRB1, DQA1 and DQB1 alleles. Other haplotypes were inferred from previously reported African haplotypes (Schnittger et al , 1997) or, if absent from this study, from African-American ( Just et al , 1997) or white Caucasian haplotypes (Noble et al , 1996). Only haplotypes found at least twice, or those that could be unequivocally identified from family data or through homozygosity, were included in the statistical analysis.…”

Section: Genotypingmentioning

confidence: 98%

HLA‐DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica

Heward

Mijovic²,

Kelly³

et al. 2002

European Journal of Immunogenetics

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Genetic susceptibility to type 1 diabetes is determined by a combination of HLA-DQ and DRB1 alleles. In the present study, HLA associations with type 1 diabetes were investigated in the Jamaican population. DRB1 and DQ genotyping was performed on 45 type 1 diabetic patients and 132 control subjects born and resident in Jamaica. The small number of patients available for study reflected the low prevalence of type 1 diabetes in Jamaica. The results were compared with those from other African heritage populations and white Caucasians. The highest relative risk was associated with the DRB1*03-DQ2/DRB1*04-DQ8 genotype. Both DRB1*0401-DQ8 and DRB1*0408-DQ8 were positively associated with disease. DRB1*0408-DQ8 is uncommon amongst white Caucasians, where DRB1*0401-DQ8 is the major predisposing haplotype. The DRB1*1503-DQ6 haplotype was associated with protection from diabetes in the Jamaican population. This haplotype is rare amongst white Caucasians, where DRB1*1501-DQ6 is the protective haplotype. Data from African heritage populations suggest that DRB1*1503-DQ6 might be less protective than DRB1*1501-DQ6. DRB1*03-DQA1*0401-DQB1*0402 was associated with protection from diabetes in the Jamaican population, whereas in white Caucasians DRB1*08-DQA1*0401-DQB1*0402 is predisposing. These data demonstrate that comparison of genetic associations with type 1 diabetes in races with population-specific DRB1-DQ haplotypes provides new information as to the exact determinants of disease susceptibility. Further support is provided for roles of the DQ genes and the DRB1 gene (or a gene in linkage disequilibrium with it) in determining susceptibility to type 1 diabetes.

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“…A final audit of the data was performed after agreement was reached on the typing results ( (12,13), and one haplotype (#74) is of Amerindian origin (14,15). All of these 'admixture' haplotypes are quite rare and were present in only one or two cases each.…”

Section: Data Validationmentioning

confidence: 99%

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

et al. 2003

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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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African‐American HLA class II allele and haplotype diversity

Cited by 53 publications

References 27 publications

Molecular typing of human leukocyte antigen and related polymorphisms following whole genome amplification

Molecular typing of human leukocyte antigen and related polymorphisms following whole genome amplification

HLA‐DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica

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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