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

Abstract

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.

Extensive HLA class II studies in 58 non‐DRB1*15 (DR2) narcoleptic patients with cataplexy

“…In one Black subject, DQCARII 202, an allele normally found in combination with DRB L :c 16, DQAl *O 1022, DQB 1 ''0502 was observed in the context of DRB 1 :k 1602, DQAPO1022, DQCAR 103, DQB1:k0602 ( Table 2). This result suggest that this susceptibility haplotype was generated by a DQA I-DQB I crossover between a DRB 1602, QAP 1.2, DQA1:#0103,2, Table 3 0OAl and DO81 gene frequencies in 37 non-DQB1'0602 -positive subjects P Approximate gene frequencies in non-DR15, non-DQB1'0602 haplotypesa 9.5% (7) 6.8% (5) 12.2%(9) 2.7% (2) 1.4%(1) 1 8.9% (1 4) 18.9°/o(14) 2.7% ( 2) 27.0% (20) f 2.2Yo (9) 2.7%(2) f .4% ( 1) t.4%(1) ' 2.7"/0 (2) (20,23,24,34,40,42). In Black A rnericans , DQ A 1 "0 1 0 1 /04/05, DQB 1'0602 have been reported by at least three independent investigators (DQA 1 *O 10 1, 0 104 or 0105 were not distinguished in these early studies) (20,23,40,42).…”

“…The haplotype in- The fact that all 21 non-DRBIW but DQB 1 *0602-positive narcoleptic subjects are also DQAl*O102 1 or DQA1*01022 positive, together with the finding that numerous genetic exchanged crossovers and microsatellite mutations in the immediate flanking region of DQBl and DQAl have occurred in some of these subjects strongly suggest that the DQB 1*0602 and DQAl*O102 molecules themselves are involved in narcolepsy suscepti bility. In Caucasian or American Black normal subjects, haplotypes with DQAl*Ol alleles other than DQA1*0102 in cis with DQBl"0602 have been reported with a frequency of approximately one for 20 to 25 DQB 1 *0602-positive control subjects (20,23,24,34,40,42). The full coding sequence of the I)QB l"0602 allele was isolated and sequenced in one of these subjects and found to be identical to reference DQB 1 *0602 sequence.…”

HLA‐DP polymorphism in the present‐day San (Bushmen) and Khoi (Hottentots) using polymerase chain reaction and sequence‐specific oligonucleotide typing

“…It is believed that, amongst others, miscegenation between Caucasoids and Khoi, and to a lesser extent between Caucasoids and San, contributed to the creation of a mixed ancestral group in South Africa (6). Several unusual HLA Class I specificities have previously been described in this group (9)(10)(11)(12)(13). In an independent observation, the DPBl*CT2 allele, the most frequent of the new alleles in the San and Khoi, was also detected in a South African family of mixed ancestry (Willem Verduynpersonal communication).…”

Diversity in HLA class I and class II in kidney donors and recipients according to race in KwaZulu-Natal (South Africa) implications for transplantation

“…Du Toit et al in a report on MHC Class I revealed variation in Black African, Coloured and Caucasians [5]. Martell et al reported the HLA Class II alleles DRw8 and DRw14 were only observed in a mixed ancestral South African population [28].…”