A study of the HLA-Dw determinants and their relationship to DR and DQ antigens in three south african population groups: South African caucasoids, South African negroes, and Cape coloureds

Oudshoorn, Machteld; Toit, E. D. du; Taljaard, D. G.; MacGregor, Ken

doi:10.1016/0198-8859(86)90279-x

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…Further, concordance between the extent of RFLPdefined variability and functional polymorphism has been described for MHC class I loci (27). These observations, the findings of the present study, and serological (16) and cellular (14,15) typing results indicate that many new HLA class II sequences or combinations of allelic sequences within a class II haplotype will be found in populations of African origin.…”

supporting

confidence: 69%

HLA-DR and -DQ gene polymorphism in West Africans is twice as extensive as in north European Caucasians: evolutionary implications.

Olerup

Troye‐Blomberg

Schreuder

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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The HLA genes are the most polymorphic coding loci known in humans. DRB-DQA-DQB gene polymorphism was investigated by Taq I restriction fragment length polymorphism analysis in more than 700 West Africans and found to be almost twice as extensive in West Africans as in North European Caucasians. This finding indicates that Africans comprise the oldest and genetically most diverse human population and supports the hypothesis of the occurrence of a population bottleneck in the emergence of the White race. As in Caucasians, less than one-third of possible cis-encoded DQA-DQB combinations were encountered, indicating constraints on the pairing of DQ a and P polypeptides. Heterozygote advantage (i.e., positive selection) was found for DRB, DQA, and DQB alleles as well as for DQA-DQB combinations. However, in West Africans as well as in North Europeans the observed frequencies of DRB-DQA-DQB homozygotes were close to neutrality expectations. Although the hypothesis that HLA polymorphism is maintained by parasite-driven overdominant selection is attractive, there is little evidence to support that view. We propose instead that one of the forces maintaining a low frequency of HLA homozygotes might be a decreased likelihood of potentially autoreactive T-cell clones escaping thymic selection in HLA heterozygotes. This would be consistent with the central role of HLA molecules as self/nonself discriminators.Most expressed HLA genes exhibit a remarkable degree of allelic polymorphism, which derives from sequence differences predominantly localized to discrete hypervariable Tegions in the amino-terminal -domains of the molecule. HLA variability influences both self-adjustment of the T-cell repertoire during thymic maturation and immune responsiveness of an individual to antigenic peptides.Major histocompatibility complex (MHC) polymorphism has several unique features: most loci have7 many alleles, no allele dominates in frequency, and alleles differ by many amino acid substitutions. Two hypotheses, retention of-ancestral polymorphisms and hypermutational diversification, have dominated speculations on the evolutionary origin of MHC diversity. The trans-species evolution theory (1)-i.e., that most major MHC allelic types diverged prior to the origin of the species in which they are found-has been supported by sequence analysis of rodent and primate MHC genes (2-5). The rate of amino acid-altering substitutions exceeds that of silent substitutions in codons of contact amino acids in the antigen-binding site of MHC class I and class II molecules, indicating that selection operates directly on the antigen-binding site (6-8). The high degree of-polymorphism, long persistence of alleles, low frequency of homozygotes, and high rate of replacement substitutions can best be explained by overdominant selection. However, the evolutionary force(s) exerting such selection pressure remain-unclear.Restriction fragment length polymorphism (RFLP) analysis of HLA class II genes, especially DR and DQ, has been developed into a powerful...

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supporting

confidence: 69%

HLA-DR and -DQ gene polymorphism in West Africans is twice as extensive as in north European Caucasians: evolutionary implications.

Olerup

Troye‐Blomberg

Schreuder

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…' The specificity HLA-Dw3 was found to be the only cellularly defined specificity associated with the DR3 antigen in a sample consist-ing mainly of Caucasoids (Grosse-Wilde et al 1984). In an investigation of the frequency of the Dw types in the various populations of South Africa, however, we were unable to assign Dw3 to the majority of South African (SA) Negroes with DR3 (r=0.297), but a good correlation of Dw3 with DR3 was observed for the SA Caucasoids (r = 0.954) and Cape Coloureds (r = 0.893) (Oudshoorn et al 1986). In the 10th International Histocompatibility Workshop, it became clear that HLA-DR3 could be split into two subgroups, DRwl7 (previously DR3.1) and DRwl8 (previously DRw3.2) (Oudshoorn et al 1987).…”

mentioning

confidence: 72%

HLA‐Dw ‘RSH’: a new HLA‐Dw specificity associated with HLA‐DRw18(3)

Oudshoorn¹,

Toit²,

Taljaard³

1989

Tissue Antigens

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The present study describes a new HLA-Dw specificity, Dw'RSH'. HLA-Dw'RSH' is associated with DRw18(3) and is clearly different to the DRw17(3) associated specificity Dw3. Dw'RSH' was shown to be the most common Dw specificity found in the South African (SA) Negroes (gf = 0.10) and was less common in Cape Coloureds (gf = 0.01). The specificity was absent in the SA Caucasoids tested. Dw'RSH' is part of the common Negro haplotype Bw42, DRw18, DQw4 which is seen as commonly in the SA Negroes as the B8, DRw17, DQw2, Dw3 haplotype is seen in the Caucasoids.

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“…Mother 12 x 6.4 52c 7.7 cd 6 a a a a a a a a a 6 a a a a a a a The specificitieslalleles mentioned are positive with the corresponding oligonucleotide. #Homozygous typing cell with specificity 'BME (1). 'Homozygous typing cell with specificity 'JOH' (1).…”

Section: The Drw8 X 14 Specificitymentioning

confidence: 99%

“…#Homozygous typing cell with specificity 'BME (1). 'Homozygous typing cell with specificity 'JOH' (1). Table 3.…”

Section: The Drw8 X 14 Specificitymentioning

confidence: 99%

“…Several methods, including serology, cellular typing and RFLPs, have been used to identify the occurrence of new HLA class I1 specificities in the populations of South Africa (1)(2)(3)(4)(5)(6). Recently, the use of the polymerase chain reaction with sequence-specific oligonucleotide typing (7) makes it possible to identify a new allele at the nucleotide sequence level by means of a unique pattern of hybridization using several probes.…”

Section: Introductionmentioning

confidence: 99%

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HLA class II specificities and haplotypes in South Africa detected using polymerase chain reaction and sequence‐specific oligonucleotide typing

Martell¹,

Arendse²,

Jacobs³

et al. 1991

Tissue Antigens

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DNA sequencing of HLA class II alleles has revealed a degree of polymorphism much greater than was expected on the basis of the standard serological typing methods. Amplification of the polymorphic second exon of the class II genes using the polymerase chain reaction, followed by hybridization with sequence-specific oligonucleotide probes, allows the unambiguous identification of alleles which could not be detected previously. Using the protocols of the Eleventh International Histocompatibility Workshop, we have applied this procedure for the typing of several individuals and their families with suspected alleles that had been observed using serology, cellular typing and restriction fragment length polymorphism (RFLPs). These included an allele related to DRw8 and DRw14, which has only been observed in the mixed ancestral South African population. In addition, unusual combinations of class II genes forming unique haplotypic associations were seen.

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A study of the HLA-Dw determinants and their relationship to DR and DQ antigens in three south african population groups: South African caucasoids, South African negroes, and Cape coloureds

Cited by 7 publications

References 18 publications

HLA-DR and -DQ gene polymorphism in West Africans is twice as extensive as in north European Caucasians: evolutionary implications.

HLA-DR and -DQ gene polymorphism in West Africans is twice as extensive as in north European Caucasians: evolutionary implications.

HLA‐Dw ‘RSH’: a new HLA‐Dw specificity associated with HLA‐DRw18(3)

HLA class II specificities and haplotypes in South Africa detected using polymerase chain reaction and sequence‐specific oligonucleotide typing

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